StudyFinder
Search Results Within Category "Dermatology/Skin Conditions "
28 Study Matches
Safety and Efficacy of Radio Frequency for the Treatment of Mild to Severe Inflammatory Acne
The aim of this trial is to evaluate the safety and efficacy of the InMode RF Pro System with the Morpheus8 face tip (24 pins) applicator for the treatment of mild, moderate and severe, facial acne vulgaris
Call 214-648-5005
studyfinder@utsouthwestern.edu, JENNIFER.BARILLAS@UTSouthwestern.edu
Jeffrey Kenkel
18673
All
16 Years and over
N/A
NCT05830968
STU-2023-0661
Inclusion Criteria:
• Subject is >16 years of age
• General good health confirmed by medical history and examination of the treated area.
• Subjects with mild to severe Acne Vulgaris, defined as a baseline IGA (Investigator's Global Assessment) score of 2, 3 or 4 and 10-100 inflammatory lesions (papules or pustules).
• The patients should be willing to comply with the study procedure and schedule, including the follow up visits, and will refrain from using any other acne treatment methods during the entire study period.
• Willing to avoid sun/UV exposure for duration of the study unless using sunscreen.
• Willing to refrain from starting or changing hormonal contraception for duration of study.
• Subject understands and is willing to sign the informed consent to participate in the study. Parental (or other) guardians must provide consent for minors under the age of
•
Exclusion Criteria:
- Pacemaker or internal defibrillator, or any other active electrical
implant anywhere in the body.
• Patients who are under pharmacological anti-acne therapy (isotretinoin or antibiotics) for the last 6 months.
• Use of botulinum toxin within prior 1 month.
• Permanent implant in the treated area such as metal plates and screws, silicone implants or an injected chemical substance
• Current or history of cancer, or premalignant condition in the treatment area.
• Severe concurrent conditions, such as cardiac disorders, epilepsy, uncontrolled hypertension, and liver or kidney diseases.
• Subject who are pregnant or nursing.
• Started or changed hormonal contraceptive within prior month of study.
• Subject is unwilling or unlikely to refrain from high UV exposure to face.
• Impaired immune system due to immunosuppressive diseases such as AIDS and HIV, or use of immunosuppressive medications.
• Patients with history of diseases stimulated by heat, such as recurrent Herpes Simplex in the treatment area
• Poorly controlled endocrine disorders, such as diabetes or thyroid dysfunction.
• Any active condition in the treatment area, such as sores, psoriasis, eczema, and rash.
• History of skin disorders, keloids, abnormal wound healing, as well as very dry and fragile skin.
• History of bleeding coagulopathies or use of anticoagulants in the last 10 days.
• Any surgery in treated area within 3 months prior to treatment.
• Subject received other treatments such as light, CO2 laser or RF in the treatment area within 6 months of study start date.
• Simultaneous participation in another investigator drug or device study or completion of the follow-up phase for the primary endpoint of any previous study less than 30 days prior to the first evaluation in this study.
• Subject that has any condition that, at the investigator's discretion, renders the subject unsuitable for participation in this clinical research study.
Device: Morpheus8 Applicator Radiofrequency device
Other Skin, Inflammatory Acne Vulgaris
UT Southwestern
Evaluating Safety and Biomarkers Using DK210 (EGFR) for Locally Advanced or Metastatic EGFR+ Tumors
This study will evaluate safety, pharmacodynamics and biomarkers of subcutaneous (SC) DK210(EGFR) given as monotherapy and in combination with immunotherapy, chemotherapy or radiation.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Syed Kazmi
177531
All
18 Years and over
Phase 1
NCT05704985
STU-2023-0521
Inclusion Criteria:
• ECOG performance status of 0-1
• Life expectancy of >3 months according to the investigator's judgment
• Solid tumors known for response on Il-2 or Il-10 and/or high expression of EGFR like all Non-small cell Lung, Skin, Head and Neck, Colon, Kidney, Bladder, Pancreatic cancers and all squamous cell carcinoma of other organs can be included with a classical histology report, specific EGFR expression or amplification reports are needed for other solid tumor types like gynecologic, prostate or triple negative breast cancer
• Measurable disease, defined as at least one (non-irradiated) lesion measurable on CT/MRI or bone scan as defined by RECIST 1.1.
• Progressive disease (PD) at study entry defined as one or more of the following criteria:
• Clinical PD with performance decline, clinical symptoms and/or observed tumor growth
• PD documented with imaging showing at least 20% growth (largest diameter) and/or new lesions
• Adequate cardiovascular, hematological, liver, and renal function.
• Subjects have failed one or more lines of systemic therapy and have not been operated on or receiving anti-cancer medication for at least 4 weeks.
• Males and females of childbearing potential must agree to use effective contraception starting prior to the first day of treatment and continuing during treatment
• Additional criteria may apply
Exclusion Criteria:
• Subjects with documented diffuse peritoneal disease or persistent abundant ascites
• Subjects with known prolonged QtC interval
• Concomitant or recent (<4 weeks or 5 half-lives of the last treatment, whichever is shorter) treatment with agents with anti-tumor activity, including immunotherapies, or experimental therapies. Bone treatments and supportive care can be continued
• Major surgery within 4 weeks, Radiation therapy for the treatment of metastases within less than 3 weeks (if single fraction of radiotherapy, then within 2 weeks) and radionuclide therapy for the treatment of metastases within 4 weeks prior to screening
• Uncontrolled intercurrent illness including, but not limited to, ongoing and uncontrolled infection (TBC, COVID or HIV patients treated with at least two anti-retroviral drugs and control of their infection with at least 500 /mm3 CD4+ T-cells in their blood and patients cured from Hepatitis B or C (i.e negativity of PCR) and liver function compatible with eligibility criteria are allowed to participate), multiple myeloma, multiple sclerosis, myasthenia gravis, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirement
• Any other conditions that, in the investigator's opinion, might indicate the subject to be unsuitable for the study
• Additional criteria may apply
Biological: DK210 (EGFR), Radiation: Radiation therapy, Biological: Immune checkpoint blockers, Drug: Chemotherapy
Kidney Cancer, Cancer, Colorectal Cancer, Head and Neck Cancer, Non Small Cell Lung Cancer, Gynecologic Cancer, Skin Cancer, Solid Tumor, Breast - Female, Breast - Male, Cervix, Colon, Kidney, Lung/Thoracic, Melanoma, skin, Other Urinary, Pancreas, Urinary Bladder, Pancreas Cancer
Cytokine, IL-2, Interleukin 2, IL-10, Interleukin 10, Oncology, Immuno-oncology, DK210(EGFR), Immunotherapy, DEKA, DEKA Biosciences
UT Southwestern
A Study of LOXO-435 in Participants With Cancer With a Change in a Gene Called FGFR3
The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-435. LOXO-435 may be used to treat cancer of the cells that line the urinary system and other solid tumor cancers that have a change in a particular gene (known as the FGFR3 gene). Participation could last up to 30 months (2.5 years) and possibly longer if the disease does not get worse.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
206021
All
18 Years and over
Phase 1
NCT05614739
STU-2023-0080
Inclusion Criteria:
• Have solid tumor cancer with an FGFR3 pathway alteration on molecular testing in tumor or blood sample that is deemed as actionable.
• Cohort A1 (Dose Escalation): Presence of an alteration in FGFR3 or its ligands.
• Cohort A2 (Dose Optimization): Histological diagnosis of urothelial cancer (UC) that is locally advanced or metastatic with a qualifying FGFR3 alteration.
• Cohorts B1, B2 and B3 (Dose Expansion): Histological diagnosis of urothelial cancer that is locally advanced or metastatic with a prespecified activating FGFR3 alteration.
• Cohort C (Dose Expansion): Must have histological diagnosis of a non-urothelial solid tumor malignancy that is locally advanced or metastatic with a prespecified activating FGFR3 alteration.
• Measurability of disease:
• Cohort A1: Measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST v1.1)
• Cohorts A2, B1, B2, B3, and C1: Measurable disease required as defined by RECIST v1.1
• Have adequate archival tumor tissue sample available or undergo a screening biopsy if allowed per country-specific regulations.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Prior Systemic Therapy Criteria:
• Cohort A1/C1: Participant has received all standard therapies for which the participant was deemed to be an appropriate candidate by the treating Investigator; OR the participant is refusing the remaining most appropriate standard of care treatment; OR there is no standard therapy available for the disease. There is no restriction on number of prior therapies.
• Cohort A2/B1/B2/B3: Participants must have received at least one prior regimen in the advanced or metastatic setting. There is no restriction on number of prior therapies.
• FGFR inhibitor specific requirements:
• Cohort A1/A2: Prior FGFR inhibitor treatment is permitted, but not required.
• Cohort B1: Participants must have been previously treated with a FGFR inhibitor.
• Cohort B2, B3, C1: Participants must be FGFR inhibitor naïve.
Exclusion Criteria:
• Participants with primary central nervous system (CNS) malignancy.
• Known or suspected history of uncontrolled CNS metastases.
• Current evidence of corneal keratopathy or retinal disorder.
• Have a history and/or current evidence of extensive tissue calcification.
• Any serious unresolved toxicities from prior therapy.
• Significant cardiovascular disease.
• Prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF).
• Active uncontrolled systemic infection or other clinically significant medical conditions.
• Participants who are pregnant, lactating, or plan to breastfeed during the study or within 6 months of the last dose of study treatment. Participants who have stopped breastfeeding may be enrolled.
Drug: LOXO-435, Drug: Pembrolizumab
Neoplasm Metastasis, Urinary Bladder Neoplasms, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Thyroid, Urinary Bladder, Kaposis sarcoma, Small Intestine, Soft Tissue, Unknown Sites, Ureteral Neoplasms
Bladder Cancer, Bladder Urothelial Carcinoma, Urinary Bladder Cancer, Urinary Tract Cancer, Renal Pelvis Cancer, Ureter Cancer
UT Southwestern
A Trial to See if the Combination of Fianlimab With Cemiplimab Works Better Than Pembrolizumab for Preventing or Delaying Melanoma From Coming Back After it Has Been Removed With Surgery
The primary objective of the study is to demonstrate superiority of fianlimab + cemiplimab compared to pembrolizumab, as measured by relapse free survival (RFS) The secondary objectives of the study are: - To demonstrate superiority of fianlimab + cemiplimab compared to pembrolizumab, as measured by overall survival (OS) - To demonstrate superiority of fianlimab + cemiplimab compared to pembrolizumab, as measured by melanoma specific survival (MSS) - To evaluate whether post-operative adjuvant therapy improves distant metastasis-free survival (DMFS), in stage IIC or III patients receiving fianlimab + cemiplimab compared to pembrolizumab - To assess impact of fianlimab + cemiplimab on quality of life as compared to pembrolizumab in adults - To assess safety and tolerability of fianlimab + cemiplimab compared to pembrolizumab - To characterize pharmacokinetics (PK) of fianlimab + cemiplimab using sparse PK sampling in patients 12 years of age and older - To assess immunogenicity of fianlimab and against cemiplimab
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Jade Homsi
175558
All
12 Years and over
Phase 3
NCT05608291
STU-2023-0248
Key
• All patients must be either stage IIC, III, or stage IV per American Joint Committee on Cancer (AJCC) 8th edition and have histologically confirmed melanoma that is completely surgically resected in order to be eligible as defined by the protocol
• Complete surgical resection must be performed within 12 weeks prior to randomization, and enrollment may occur only after satisfactory wound healing from the surgery
• All patients must have disease-free status documented by a complete physical examination and imaging studies within 4 weeks prior to randomization, as described in the protocol Key
• Uveal melanoma
• Any evidence of residual disease after surgery by imaging, pathology, or cytology.
• Ongoing or recent (within 2 years) evidence of clinically significant autoimmune disease that required systemic treatment with immunosuppressive agents
• Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C (HCV) infection; or diagnosis of immunodeficiency that is related to, or results in chronic infection, as described in the protocol
• Another malignancy that is currently progressing or that required active treatment in the past 5 years, as described in the protocol
• Adolescent patients (≥12 to <18 years old) with body weight <40 kg Note: Other Protocol Defined Inclusion/ Exclusion Criteria Apply
Inclusion Criteria:
• All patients must be either stage IIC, III, or stage IV per American Joint Committee on Cancer (AJCC) 8th edition and have histologically confirmed melanoma that is completely surgically resected in order to be eligible as defined by the protocol
• Complete surgical resection must be performed within 12 weeks prior to randomization, and enrollment may occur only after satisfactory wound healing from the surgery
• All patients must have disease-free status documented by a complete physical examination and imaging studies within 4 weeks prior to randomization, as described in the protocol Key
Exclusion Criteria:
• Uveal melanoma
• Any evidence of residual disease after surgery by imaging, pathology, or cytology.
• Ongoing or recent (within 2 years) evidence of clinically significant autoimmune disease that required systemic treatment with immunosuppressive agents
• Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C (HCV) infection; or diagnosis of immunodeficiency that is related to, or results in chronic infection, as described in the protocol
• Another malignancy that is currently progressing or that required active treatment in the past 5 years, as described in the protocol
• Adolescent patients (≥12 to <18 years old) with body weight <40 kg Note: Other Protocol Defined Inclusion/ Exclusion Criteria Apply
Drug: Fianlimab, Drug: Cemiplimab, Drug: Pembrolizumab, Drug: Placebo
Melanoma, Melanoma, skin
Resected High Risk Melanoma, Skin Cancer, Stage IIC, Stage III, Stage IV, LAG-3 Lymphocyte activation gene 3, Adjuvant Setting, anti-PD-1 Monoclonal Antibody
UT Southwestern
A Study of LOXO-783 in Patients With Breast Cancer/Other Solid Tumors (PIKASSO-01)
The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-783. LOXO-783 may be used to treat breast cancer and other solid tumors that have a change in a particular gene (known as the PIK3CA gene). Participation could last up to 36 months (3 years) and possibly longer if the disease does not get worse.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Nisha Unni
148963
All
18 Years and over
Phase 1
NCT05307705
STU-2022-0511
Inclusion Criteria:
• Have advanced breast cancer or another solid tumor with the presence of a phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) H1047R mutation (or other Sponsor and safety review committee (SRC)-approved, activating PIK3CA mutations other than H1047R mutation)
• Have adequate archival tumor tissue sample available or be approved by the Sponsor for enrollment if no tumor sample is available.
• Have stopped all cancer treatment and have recovered from the major side effects
• Have adequate organ function, as measured by blood tests
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
• Patients must have
• Measurable disease --- Patients with non-breast tumor types must have at least 1 measurable lesion
• Non-measurable bone disease (at least 1 bone lesion in breast cancer patients only)
• For patients with an estrogen receptor (ER)+ breast cancer diagnosis:
• If female, must be postmenopausal
• If male, must agree to use hormone suppression
• Phase 1a: -- Dose escalation and backfill patients:
• Advanced solid tumor
• Patients may have had up to 5 prior regimens for advanced disease
• Phase 1b:
• Part A:
• ER+/human epidermal growth factor receptor 2 (HER2)- advanced breast cancer
• Patients may have had up to 5 prior regimens for advanced disease ---- Prior cyclin dependent kinase (CDK)4/6 inhibitor therapy required
• Part B:
• ER+/HER2- advanced breast cancer
• Patients may have had up to 2 prior regimens for advanced disease.
• Part C:
• ER+/HER2- advanced breast cancer
• Patients may have had up to 5 prior regimens for advanced disease. ---- Prior CDK4/6 inhibitor therapy required.
• Have a diagnosis of diabetes mellitus Type 2
• Part D:
• Advanced breast cancer
• Patients may have had up to 5 prior regimens for advanced disease.
• Part E:
• Advanced solid tumor
• Patients may have had up to 3 prior regimens for advanced disease advanced disease
• Part F:
• ER+/HER2- advanced breast cancer
• Patients may have had up to 5 prior regimens for advanced disease
• Prior cyclin dependent kinase (CDK)4/6 inhibitor therapy required
Exclusion Criteria:
• Medical Conditions
• Colorectal cancer
• Endometrial cancers with specific concurrent oncogenic alterations
• A history of known active or suspected
• Diabetes mellitus Type 1 or
• Diabetes mellitus Type 2 requiring antidiabetic medication (Phase 1a and all parts of Phase 1b except Part C).
• Serious concomitant systemic disorder
• Known or suspected history of untreated or uncontrolled central nervous system (CNS) involvement.
• Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection, or other clinically significant active disease process
• Prior exposure to phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) inhibitor(s), except in certain circumstances
Drug: LOXO-783, Drug: Fulvestrant, Drug: Imlunestrant, Drug: Abemaciclib, Drug: Anastrozole, Exemestane, or Letrozole, Drug: Paclitaxel
Breast Cancer, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Thyroid, Kaposis sarcoma, Small Intestine, Soft Tissue, Unknown Sites
UT Southwestern; Parkland Health & Hospital System
Pediatric Radiation Oncology With Movie Induced Sedation Effect (PROMISE)
PROMISE (Pediatric Radiation Oncology with Movie Induced Sedation Effect) is an interactive incentive-based movie system that integrates with a video surveillance gating module (VisionRT) as an alternative sedation solution for pediatric patients undergoing radiation treatment (RT). This single-arm, open label, single-center phase II clinical trial is to implement PROMISE for all children ages 3-11 who are planned to undergo RT at the institution. The primary goal is to decrease the total number of pediatric patients who require general anesthesia through the use of PROMISE, with secondary goals being to assess the impact that PROMISE has on patient/family anxiety and quality of life, treatment time and clinical efficiency, and overall cost. The investigators hypothesize that PROMISE will lead to a reduction in the percentage of patients ages 3-7 who require general anesthesia use from 70% (historical control) to 30%.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kiran Kumar
181795
All
3 Years to 11 Years old
Phase 2
NCT05148078
STU-2021-1005
Inclusion Criteria:
• Planned to undergo radiation treatment
• Age 3-11 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at screening
• Parents or guardians with the ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
• Subjects with documented medical behavior conditions or other conditions necessitating anesthesia use
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects whose parents opt to not include them (the subject) in the clinical trial.
Other: PROMISE (Pediatric Radiation Oncology with Movie Induced Sedation Effect)
Multiple Myeloma, Pediatric Cancer, Brain and Nervous System, Eye and Orbit, Bones and Joints, Kidney, Lip, Oral Cavity and Pharynx, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Rectum, Thyroid, Leukemia, Other, Leukemia, Not Otherwise Specified, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Non-Hodgkins Lymphoma, Other Hematopoietic, Soft Tissue
radiotherapy
UT Southwestern; Children’s Health
Vitamin D Deficiency in Adults Following a Major Burn Injury
This is a single site double blind randomized controlled trial of replacing Vitamin D for Vitamin D-deficient burn patients at a current recommended dose (400 IU daily) versus a higher dose (4000 IU daily). Capsules will be made in a compounding pharmacy and will look identical. Randomized controlled trial. People who meet the selection criteria will be randomized to either low or high dosage of Vitamin D. Treatment arm is high dose Vitamin D (4000 IU), and control is low dose Vitamin D (400 IU). Main outcome variables include PROMIS-29 measures of physical health, mental health and social health, the Veterans RAND 12 Item Health Survey (VR-12), and the 4-D Itch Scale. Secondary outcome variables include subject demographics, injury demographics and characteristics.
Call 214-648-5005
studyfinder@utsouthwestern.edu, KyraJeanine.Solis-Beach@UTSouthwestern.edu
Karen Kowalske
14019
All
18 Years and over
Phase 4
NCT05084248
STU-2019-1223
Inclusion Criteria:
• Adults, 18 years of age or older, who have completed 6 months from time of their burn injury
• ≥ 10% TBSA, ≥ 65 years of age and Burn Surgery for Wound Closure
• ≥ 20% TBSA, 18 - 64 of age and Burn Surgery for Wound Closure
• Electrical high voltage / lightning and Burn Surgery for Wound Closure
• Hand burn and/or face burn, and/or feet burn and Burn Surgery for Wound Closure
• May speak English or Spanish
• Vit. D deficiency
Exclusion Criteria:
• Patients with parathyroid disease, severe liver dysfunction, sever kidney dysfunction, which are not caused by the burn injury
• Patients with malignant tumors
• Patients not meeting the inclusion criteria
Drug: Ergocalciferol Capsules
Burns, Vitamin D Deficiency
UT Southwestern; Parkland Health & Hospital System
Study of Zirconium Zr 89 Crefmirlimab Berdoxam PET/CT in Subjects With Advanced or Metastatic Malignancies (iPREDICT)
The purpose of this study is to evaluate whether zirconium Zr 89 crefmirlimab berdoxam (other names 89Zr-crefmirlimab berdoxam, 89Zr-Df-crefmirlimab, 89Zr-Df-IAB22M2C) PET/CT can predict the response of advanced or metastatic melanoma, Merkel cell carcinoma, renal cell carcinoma, or non-small cell lung cancer tumors to immuno-oncology therapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
James Brugarolas
80679
All
18 Years and over
Phase 2
NCT05013099
STU-2022-0390
Inclusion Criteria:
• Subjects will be eligible for enrollment in the study if they meet ONE criteria a, b or c in point 1 and ALL the criteria in points 2-9.
• Subjects must meet ONE of the criteria a, b or c below:
• For enrollment into Cohort A: Subjects with histologically confirmed advanced or metastatic non-uveal/non-mucosal melanoma or merkel cell carcinoma (MCPyV positive and negative) who are not amenable to surgical cure and are candidates to receive single- or combined IOT alone (not to include cytotoxic chemotherapy) as first or second line treatment.
• For enrollment into Cohort B: Subjects with histologically confirmed advanced or metastatic clear cell Renal Cell Carcinoma or Renal Cell Carcinoma with sarcomatoid features (regardless of subtype) as defined on pathologic examination by a component of clear cell or sarcomatoid, who are not amenable to surgical cure and are candidates to receive single- or combined IOT alone or IOT in combination with VEGFR-directed or tyrosine kinase inhibitor (not to include cytotoxic chemotherapy) as first or second line treatment
• For enrollment into Cohort C: Subjects with histologically confirmed advanced or metastatic non-small cell lung cancer without non-smoker/driver mutations who are not amenable to surgical cure, and are candidates to receive single- or combined IOT alone (not to include cytotoxic chemotherapy) as first or second line treatment as per the label/prescribing information at the physicians discretion. i. Patients with driver mutations that are expected to show significant benefit from first line checkpoint inhibiter treatment (such as KRAS G12C mutations) are eligible if all other I/E criteria are met Subjects must meet All of the criteria 2-9 below:
• At least 1 RECIST 1.1-measurable. non-irradiated, non-osseous (unless there is an associated measurable soft-tissue component) lesion documented on intravenous (IV) contrast-enhanced CT or MRI (per RECIST criteria 1.1) prior to first zirconium Zr 89 crefmirlimab berdoxam administration.
• Has an adequate amount of time between their prior treatment/procedure and the 1st administration of zirconium Zr 89 crefmirlimab berdoxam.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2 and anticipated survival of at least 6 months.
• Meeting all clinical safety lab values per institution's SOC, or investigator's discretion, for subjects receiving cancer treatment.
• Male or female age ≥18 years.
• Ability to understand the purposes and risks of the trial and has signed an Institutional Review Board (IRB) approved informed consent form.
• Willingness and ability to comply with all protocol required procedures.
• For men and women of child-producing potential, use of effective double barrier contraceptive methods during the study, up to 30 days after the last administration of the investigational product.
Exclusion Criteria:
• Subjects will NOT be eligible for enrollment in the study if they meet ANY of the following criteria:
• Bone-only disease without a measurable soft tissue component on conventional imaging (MRI, PET, CT).
• Subjects with skin-only (cutaneous) lesions will be excluded from the tumor biopsy assessment.
• Serious nonmalignant disease, additional active malignant disease or conditions that in the opinion of the investigator and/or ImaginAb could compromise protocol objectives.
• Subjects with splenic dysfunction or who are status post splenectomy. Post-splenectomy subjects who develop an accessory spleen with clinical and radiographic evidence of splenic function will be allowed with prior approval from the Sponsor.
• Corticosteroid therapy is prohibited if used for the treatment of inflammatory or autoimmune conditions. Patients with adrenal insufficiency from prior surgery or immunotherapy toxicity may be on standard chronic replacement doses of hydrocortisone that also require sporadic use of stress doses of steroid .
• Pregnant women or nursing mothers.
Biological: zirconium Zr 89 crefmirlimab berdoxam
Melanoma, Renal Cell Carcinoma, Non Small Cell Lung Cancer, Kidney, Lung/Thoracic, Melanoma, skin, Other Skin, Merkel Cell Carcinoma, Unspecified
UT Southwestern
Allergic Disease Onset Prevention Study (adored)
This is a Phase 1b/2, randomized, double-blind, multi-center study to evaluate the safety, tolerability, and preliminary clinical efficacy of STMC-103H in neonates and infants at risk for developing allergic disease (Type 1 hypersensitivity). Subjects will be enrolled in a three-part sequential approach. Participants in the safety-run portion of the study (Part A1: 1 year to <6 years of age and A2: 1 month to <12 months of age) will receive 28 days of treatment with STMC-103H or placebo, followed by 28 days of follow-up. A Data and Safety Monitoring Committee (DSMC) will review safety data after all patients in each part complete 28 days of therapy prior to enrolling the next part. After A2, Part B will enroll 224 patients for 336 days of treatment with STMC-103H or placebo, followed by 336 days of follow-up. Stool, blood, and optional samples will be collected in Parts A2 and part B. Primary safety endpoints are frequency, type and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs), as well as findings on physical exams, vitals, and safety laboratories. The primary efficacy endpoint is incidence of physician-diagnosed atopic dermatitis at day 336.
Call 214-648-5005
studyfinder@utsouthwestern.edu, DOLORES.SANTOYO@UTSouthwestern.edu
John Bird
108478
All
0 Days to 14 Days old
Phase 1/Phase 2
NCT05003804
STU-2021-0965
Inclusion Criteria:
• All Parts (A1, A2, B)
• Subject's parent(s)/legal representative(s) providing consent must be 18 years or older
• Biological mother and/or biological father and/or full sibling(s), have a history of asthma, atopic dermatitis, food allergy, or allergic rhinitis as determined by the screening questionnaire
• Subject's parent(s)/legal representative(s) (if appropriate according to local laws) is/are willing and able to give informed consent for participation in the study
• Subject's parent(s)/legal representative(s) (if appropriate according to local laws) is/are willing and able, in the PI's opinion, to comply with all study requirements Part A1 Only Inclusion criteria 1-4 for all parts plus: 5 (A1). Subject is between 1 year and < 6 years old at the time of enrollment Part A2 Only Inclusion criteria 1-4 for all parts plus: 5 (A2). Subject is between 28 days and < 12 months of life at the time of enrollment 6 (A2). Subject's parent(s)/legal representative(s) do not plan to give probiotics (including infant formula that contain probiotics) to the subject during the trial Part B Only Inclusion criteria 1-4 for all parts plus: 5 (B). Subject is ≤ 14 days of life at the time of enrollment. Sites should make every effort to enroll newborns as soon as possible after birth. 6 (B). Subject has a birthweight ≥ 2.5 kg and ≤ 4.5 kg 7 (B). Subject's parent(s)/legal representative(s) do not plan to give probiotics (including infant formula that contain probiotics) to the subject from the time of birth to the end of the trial.
Exclusion Criteria:
• All Parts (A1, A2, B)
• Subject's twin (or higher order multiple) is enrolled in STMC-103H-102
• Subject has any congenital abnormalities or condition, significant disease, illness, physical exam finding, or disorder that, in the opinion of the PI, may put the subject at safety risk or is likely to hinder feeding or affect metabolism that may influence the results of the study. (Neonatal hyperbilirubinemia (jaundice), including jaundice that requires phototherapy, should not be considered exclusionary).
• Subject is acutely ill or on systemic antibiotics at the time of enrollment
• Subject is participating in another interventional clinical study involving investigational medication, formula, probiotic, or prebiotic use within 30 days (or five half-lives, whichever is longer) of this study
• Subject has evidence of immune deficiency/immune compromise in the judgment of the investigator Part B Only Exclusion Criteria 1-5 for all parts plus: 6 (B). Subject was born at < 35 weeks' gestation 7 (B). Biological maternal medical condition during the pregnancy that, in the opinion of the PI, may put the subject at risk because of participation in the study. (Maternal antibiotics during the time of delivery should not be considered exclusionary.)
Biological: STMC-103H, Biological: Placebo
Atopic Dermatitis, Type 1 Hypersensitivity
UT Southwestern; Children’s Health
Olanzapine Versus Megestrol Acetate for the Treatment of Loss of Appetite Among Advanced Cancer Patients
This phase III trial compares the effects of olanzapine versus megestrol acetate in treating loss of appetite in patients with cancer that has spread to other places in the body (advanced). Olanzapine may stimulate and increase appetite. This study aims to find out if olanzapine is better than the usual approach (megestrol acetate) for stimulating appetite and preventing weight loss.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Namrata Peswani
193600
All
18 Years and over
Phase 3
NCT04939090
STU-2021-1170
Inclusion Criteria:
• Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom)
• Diagnosis of advanced cancer
• Patient-reported 2-month weight loss of at least 5 pounds (2.3 kilograms) and/or physician-estimated caloric intake of less than 20 calories/kilogram of body weight per day
• The patient must perceive loss of appetite and/or weight as a problem; and have an appetite score of 4 or worse on the "Please rate your appetite…." question that requires a patient response on a 0-10 numeric rating scale
• Not receiving ongoing tube feedings or parenteral nutrition at the time of registration
• Not currently using systemic adrenal steroids (with the exception of short-term dexamethasone within 3 days of chemotherapy for control of chemotherapy side effects)
• No use of androgens, progesterone analogs, or other appetite stimulants within the past month
• Patient should not have poorly controlled hypertension or congestive heart failure at registration
• Patient should not have an obstruction of the alimentary canal, malabsorption, or intractable vomiting (defined as vomiting more than 3 times per day over the preceding week)
• Not currently using olanzapine for another medical condition or had previously used olanzapine for chronic nausea or for any pre-existing psychotic disorder
• Patient should not have had a previous blood clot at any time in the past
• No history of poorly controlled diabetes
• No symptomatic leptomeningeal disease or known brain metastases as these patients may have difficulty taking oral medications
• No history of hypersensitivity to olanzapine or megestrol acetate
• No COVID-19 infection in the past that, in the opinion of the treating physician, had left patients with compromised taste, which has not resolved at the time of registration
• Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done =< 14 days prior to registration is required
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
• Estimated life expectancy of 3 months or longer
• Serum creatinine =< 2.0 mg/dL
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN)
• Fasting glucose < 140 mg/dL
• Granulocytes > 1000/hpf
• No treatment with another antipsychotic agent, such as risperidone, quetiapine, clozapine, butyrophenone within 30 days of enrollment
• In order to complete the mandatory patient-completed measures, participants must be able to speak and/or read English or Spanish. Sites seeking to enroll Spanish-speaking patients should have access to Spanish speaking staff on site or through the use of a translation service to be able to conduct the informed consent discussion in Spanish, and to conduct the weekly phone calls
Exclusion Criteria:
• Psychiatric illness which would prevent the patient from giving informed consent
• Medical condition such as uncontrolled infection (including human immunodeficiency virus [HIV]), uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
• Patients who cannot swallow oral formulations of the agents
• Patients with impaired decision-making capacity (such as with a diagnosis of dementia or memory loss) are not eligible for this study
• No presence of a hormone-sensitive tumor, such as breast, endometrial, or prostate cancer (this exclusion criterion is intended to circumvent any confounding antineoplastic effects of megestrol acetate)
Drug: Olanzapine, Drug: Megestrol Acetate, Other: Questionnaire Administration
Lymphoma, Sarcoma, Anorexia, Multiple Myeloma, Mycosis Fungoides, Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm, Brain and Nervous System, Other, Eye and Orbit, Anklylosing Spondylitis, Anus, Bones and Joints, Breast - Female, Breast - Male, Carcinoid Tumor, Cardiovascular, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Leukemia, Other, Hodgkins Lymphoma, Heart, Kaposis sarcoma, Leukemia, Not Otherwise Specified, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Non-Hodgkins Lymphoma, Other Hematopoietic, Psychiatric Disorders, Small Intestine, Soft Tissue, Unknown Sites, Ill - Defined Sites
UT Southwestern
Cryopreserved Human Umbilical Cord (TTAX01) for Late Stage, Complex Non-healing Diabetic Foot Ulcers (AMBULATE DFU II)
It is hypothesized that application at 4-week or greater intervals of the human placental umbilical cord tissue TTAX01 to the surface of a well debrided, complex diabetic foot ulcer (DFU) will, with concomitant management of infection, result in a higher rate of wounds showing complete healing within 25 weeks of initiating therapy, compared with standard care alone. This second confirmatory Phase 3 study examines a population of diabetic foot ulcer patients having adequate perfusion, with or without neuropathy, and a high suspicion of associated osteomyelitis in a complex, high grade wound.
Call 214-648-5005
studyfinder@utsouthwestern.edu, LARRY.LAVERY@UTSouthwestern.edu
Lawrence Lavery
116716
All
18 Years and over
Phase 3
NCT04450693
STU-2020-1367
Inclusion Criteria:
• The subject has signed the informed consent form
• The subject is male or female, at least 18 years of age inclusive at the date of Screening
• The subject has confirmed diagnosis of Type I or Type II diabetes
• The subject's index ulcer is located on the plantar surface, inter digital, heel, lateral or medial surface of the foot
• The subject has an index ulcer with visible margins having an area ≤ 12.0 cm2 when measured by the electronic measuring device at Screening
• The subject's index ulcer extends beyond the dermis, into subcutaneous tissue with evidence of exposed bone, tendon, muscle and/or joint capsule
• The subject presents with history, signs or symptoms leading to a clinical suspicion of osteomyelitis in the opinion of the Investigator supported by positive Probe to Bone (PTB) and any of the following: radiographic (X-ray, Magnetic Resonance Imaging (MRI), or bone scan) or evidence of bone necrosis
• The subject has an Ankle-Brachial Index ≥ 0.7 to ≤ 1.3 or TcPO2 ≥ 40 mmHg on the dorsum of the affected foot, or Great Toe Pressure ≥ 50 mmHg
• The subject is under the care of a physician for the management of Diabetes Mellitus
• The subject is willing to return for all mandatory visits as defined in the protocol
• The subject is willing to follow the instructions of the trial Investigator
Exclusion Criteria:
• The subject's index ulcer is primarily located on the dorsal surface of the foot
• The subject's index ulcer can be addressed by primary closure through the completion of the initial or staged surgical procedure
• The subject has a contralateral major amputation of the lower extremity
• The subject has a glycated hemoglobin A1c (HbA1c) level of > 12% †
• The subject has been on oral steroid use of > 7.5 mg daily for greater than seven (7) consecutive days in 30 days before Screening
• The subject has been on parenteral corticosteroids, or any cytotoxic agents for seven consecutive days in the period of 30 days before Screening
• The subject is currently taking the type 2 diabetes medicine canagliflozin (Invokana™, Invokamet™, Invokamet XR™)
• The subject has malignancy or a history of cancer, other than non-melanoma skin cancer, in five years before Screening
• The subject is pregnant
• The subject is a nursing mother
• The subject is a woman of child-bearing potential who is unwilling to avoid pregnancy or use an appropriate form of birth control (adequate birth control methods are defined as: topical, oral, implantable, or injectable contraceptives; spermicide in conjunction with a barrier such as a condom or diaphragm; intrauterine contraceptive device; or surgical sterilization of partner).
• The subject is unable to sustain off-loading as defined by the protocol
• The subject has an allergy to primary or secondary dressing materials used in this trial
• The subject has an allergy to glycerol
• The subject's index ulcer is over an acute Charcot deformity
• The subject has had previous use of NEOX®, CLARIX®, or TTAX01 applied to the index ulcer
• Per Investigator's discretion the subject is not appropriate for inclusion in the trial, e.g., undergoing surgical treatments listed in the protocol or the subject currently has sepsis, i.e., life-threatening organ dysfunction caused by a dysregulated host response to infection
Biological: TTAX01, Other: Standard care
Diabetic Foot Infection, Non-healing Wound, Non-healing Diabetic Foot Ulcer
UT Southwestern; Parkland Health & Hospital System
Assessment of Safety and Effectiveness of NovoSorb® BTM in Severe Burns
This is a multi-center, pivotal study to assess the safety and effectiveness of a new method of treating severe burns using NovoSorb® Biodegradable Temporizing Matrix (BTM).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Molly.Sperry@UTSouthwestern.edu
Samuel Mandell
205379
All
18 Years to 75 Years old
N/A
NCT04090424
STU-2022-0976
Inclusion Criteria:
• Provide written informed consent directly or via legal representative prior to any clinical study procedures being performed
• Willing to comply with all study procedures and expects to be available for the duration of the study
• Male and females ≥ 18 years of age and ≤ 75 years of age
• Patients with deep dermal or full thickness burns between 3% and 60%, inclusive, of their total body surface area (TBSA). Types of burns include the following:
• Scalding including from hot water, cooking oil, grease
• Flame
• Flash
• Contact
• Subjects who have staged surgical procedures planned e.g., one procedure to excise the burn injury and a later procedure to prepare the wound bed and apply an autologous skin graft.
• The minimum total area across all lesions to have NovoSorb® BTM applied is 3% TBSA
• Females, who are non-pregnant, naturally postmenopausal, or who agree to use effective contraceptive methods throughout the course of the study.
Exclusion Criteria:
• Has a known hypersensitivity to polyurethane
• Only a non-burn injury has been experienced by the subject including soft-tissue degloving and friction burn/crush, i.e., road rash
• Multiple traumas, i.e., significant traumatic injury to a solid organ in addition to skin
• Presence of a medical condition with a life expectancy of less than 12 months, such as advanced malignancy
• Presence of a medical condition that might interfere with treatment evaluation; or require a change in therapy including but not limited to, significant immune deficiency, or skin or vascular diseases in the area of the wound
• For females - has known or suspected pregnancy, planned pregnancy, or during lactation
• Has exposure to any other investigational agent within the last 6 months
• Has exposure to any other treatment/device that will interfere with NovoSorb® BTM integration
• Anticipated inability to perform wound care and follow-up procedures
• Anticipates of a level of non-compliance
• The use of off-label treatments for full-thickness / deep-dermal burns is not permitted
• Clinical signs of wound infection at areas to be potentially treated using NovoSorb® BTM that in the opinion of the investigator may compromise safety and study objectives
• The use of NovoSorb® BTM on the face and in the perineum area is not permitted
Device: NovoSorb BTM, Procedure: Standard of Care
Burns, Other Skin
UT Southwestern; Parkland Health & Hospital System
A Study of FF-10850 Topotecan Liposome Injection in Advanced Solid Tumors
To determine the safety profile, maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and recommended Phase 2 dose (RP2D) of FF-10850 (topotecan liposome injection) in patients with advanced solid tumors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Sanjay Chandrasekaran
202923
All
18 Years and over
Phase 1
NCT04047251
STU-2022-0554
Inclusion Criteria:
Patients must meet all the following criteria to participate in the study:
• Males and females ≥ 18 years of age
• Dose-escalation phase: Histologically or cytologically confirmed metastatic and/or unresectable solid tumor, relapsed or refractory to standard therapy, or for which no standard therapy is available that is expected to improve survival by at least 3 months
• At least 3 weeks beyond the last chemotherapy (or 3 half-lives, whichever is shorter), radiotherapy, major surgery, or experimental treatment, and recovered from all acute toxicities (≤ Grade 1), prior to the first dose of FF-10850
• Adequate performance status: Eastern Cooperative Oncology Group (ECOG) ≤ 1
• Life expectancy of ≥ 3 months
• Adequate hematologic parameters without ongoing transfusion support:
• Hemoglobin (Hb) ≥ 9 g/dL
• Absolute neutrophil count (ANC) ≥ 1.0 × 109 cells/L
• Platelets ≥ 100 × 109 cells/L
• Creatinine ≤ 1.5 × ULN, or calculated creatinine clearance ≥ 50 mL/minute by either the Cockcroft-Gault formula or as measured by a 24-hour urine collection
• Total bilirubin ≤ 2 × ULN unless due to Gilbert's disease; patients with Gilbert's disease who have a total bilirubin > 6 mg/dL are to be excluded
• ALT and AST ≤ 2.5 times ULN, or < 5 × ULN for patients with liver metastases
• QT interval corrected for rate (QT interval corrected for rate using Fridericia's Correction Formula, QTcF) ≤ 470 msec for women and ≤ 450 msec for men on the ECG obtained at Screening and confirmed pre-treatment on Cycle 1 Day 1.
• Patient must be willing to undergo a tumor biopsy, if the patient has a biopsy-accessible tumor
Exclusion Criteria:
• Patients who have not received standard/approved therapies expected to improve survival by at least 3 months
• History of severe hypersensitivity reactions to topotecan
• Serious cardiac condition within the last 6 months, such as uncontrolled arrhythmia, myocardial infarction, unstable angina or heart disease defined by the New York Heart Association (NYHA) Class III or Class IV or hereditary long QT syndrome
• Concomitant medication(s) that may cause QTc prolongation or induce Torsades de Pointes, except for antimicrobials that are used as standard of care to prevent or treat infections and other such drugs that are considered by the Investigator to be essential for patient care
• Active central nervous system (CNS) malignant disease in patients with a history of CNS malignancy. Patients with previously treated stable brain metastases are allowed if they have been stable off steroid therapy for at least 4 weeks.
• Known positive for human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HBsAg) or hepatitis C virus (HCV)
• Active infection requiring intravenous (IV) antibiotic usage within the last week prior to study treatment
• Any other medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence to study requirements or confound the interpretation of study results
• Pregnant or breast-feeding
Drug: FF-10850 Topotecan Liposome Injection
Advanced Solid Tumors, Other Skin
UT Southwestern
Study of Adjuvant Cemiplimab Versus Placebo After Surgery and Radiation Therapy in Patients With High Risk Cutaneous Squamous Cell Carcinoma
The primary objective of the study is to compare disease-free survival (DFS) of patients with high-risk cutaneous squamous cell carcinoma (CSCC) treated with adjuvant cemiplimab, versus those treated with placebo, after surgery and radiation therapy (RT). The secondary objectives of the study are: - To compare the overall survival (OS) of high-risk CSCC patients treated with adjuvant cemiplimab, versus those treated with placebo, after surgery and RT - To compare the effect of adjuvant cemiplimab with that of placebo on patients' freedom from locoregional recurrence (FFLRR) after surgery and RT - To compare the effect of adjuvant cemiplimab with that of placebo on patients' freedom from distant recurrence (FFDR) after surgery and RT - To compare the effect of adjuvant cemiplimab with that of placebo on the cumulative incidence of second primary CSCC tumors (SPTs) after surgery and RT - To evaluate the safety of adjuvant cemiplimab and that of placebo in high-risk CSCC patients after surgery and RT - To assess cemiplimab pharmacokinetics and immunogenicity in human serum
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Jade Homsi
175558
All
18 Years and over
Phase 3
NCT03969004
STU-2019-1140
Key
• For Japan only, men and women ≥21 years old
• Patient with resection of pathologically confirmed CSCC (primary CSCC lesion only, or primary CSCC with nodal involvement, or CSCC nodal metastasis with known primary CSCC lesion previously treated within the draining lymph node echelon), with macroscopic gross resection of all disease
• High risk CSCC, as defined in the protocol
• Completion of curative intent post-operative radiation therapy (RT) within 2 to 10 weeks of randomization
• Eastern Cooperative Oncology Group performance status (ECOG PS) ≤1
• Adequate hepatic, renal, and bone marrow function as defined in the protocol Key
• Squamous cell carcinomas (SCCs) arising in non-cutaneous sites as defined in the protocol
• Concurrent malignancy other than localized CSCC and/or history of malignancy other than localized CSCC within 3 years of date of randomization as defined in the protocol
• Patients with hematologic malignancies (note: patients with chronic lymphocytic leukemia (CLL) are not excluded if they have not required systemic therapy for CLL within 6 months of enrollment)
• Patients with history of distantly metastatic CSCC (visceral or distant nodal), unless the disease-free interval is at least 3 years (regional nodal involvement of disease in draining lymph node basin that was resected and radiated prior to enrollment will not be exclusionary)
• Ongoing or recent (within 5 years of randomization date) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events (irAEs). The following are not exclusionary: vitiligo, childhood asthma that has resolved, type 1 diabetes, residual hypothyroidism that required only hormone replacement, or psoriasis that does not require systemic treatment.
• Has had prior systemic anti-cancer immunotherapy for CSCC Note: Other protocol defined Inclusion/Exclusion criteria apply
Inclusion Criteria:
• For Japan only, men and women ≥21 years old
• Patient with resection of pathologically confirmed CSCC (primary CSCC lesion only, or primary CSCC with nodal involvement, or CSCC nodal metastasis with known primary CSCC lesion previously treated within the draining lymph node echelon), with macroscopic gross resection of all disease
• High risk CSCC, as defined in the protocol
• Completion of curative intent post-operative radiation therapy (RT) within 2 to 10 weeks of randomization
• Eastern Cooperative Oncology Group performance status (ECOG PS) ≤1
• Adequate hepatic, renal, and bone marrow function as defined in the protocol Key
Exclusion Criteria:
• Squamous cell carcinomas (SCCs) arising in non-cutaneous sites as defined in the protocol
• Concurrent malignancy other than localized CSCC and/or history of malignancy other than localized CSCC within 3 years of date of randomization as defined in the protocol
• Patients with hematologic malignancies (note: patients with chronic lymphocytic leukemia (CLL) are not excluded if they have not required systemic therapy for CLL within 6 months of enrollment)
• Patients with history of distantly metastatic CSCC (visceral or distant nodal), unless the disease-free interval is at least 3 years (regional nodal involvement of disease in draining lymph node basin that was resected and radiated prior to enrollment will not be exclusionary)
• Ongoing or recent (within 5 years of randomization date) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events (irAEs). The following are not exclusionary: vitiligo, childhood asthma that has resolved, type 1 diabetes, residual hypothyroidism that required only hormone replacement, or psoriasis that does not require systemic treatment.
• Has had prior systemic anti-cancer immunotherapy for CSCC Note: Other protocol defined Inclusion/Exclusion criteria apply
Drug: Cemiplimab, Drug: Placebo
Cutaneous Squamous Cell Carcinoma
High risk
UT Southwestern
Cycled Phototherapy
Cycled phototherapy (PT) is likely to increase survival over that with continuous PT among extremely premature infants (< 750 g BW or <27 weeks GA).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Michelle.Harrod@UTSouthwestern.edu
Myra Wyckoff
19272
All
22 Weeks to 27 Weeks old
N/A
NCT03927833
STU-2019-0854
Inclusion Criteria:
• Infants is inborn
• Infant is ≤ 750 grams at birth and/or < 27 weeks gestation at birth by best OB estimate
• Infant is 12-36 hours of age.
Exclusion Criteria:
• Unable to enroll infant by 36 hours of age
• Previous phototherapy
• Known hemolytic disease
• TSB reported as >6.0 mg/dL before 12 hours age
• Major anomaly
• Overt nonbacterial infection
• Infant is likely to expire soon: Limiting or withdrawal of intensive care is being recommended to the parents, the parents are requesting withdrawal of care, or the pH is < 6.80 or persistent bradycardia with hypoxemia for >2h.
Device: Phototherapy lights
Hyper Bilirubinemia, Premature Infant, Other Skin
Infant, Newborn, Diseases, Phototherapy
UT Southwestern; Children’s Health; Parkland Health & Hospital System
Study Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumors
A study to learn about safety and find out maximum tolerable dose of palbociclib given in combination with chemotherapy (temozolomide with irinotecan or topotecan with cyclophosphamide) in children, adolescents and young adults with recurrent or refractory solid tumors (phase 1). Neuroblastoma tumor specific cohort to further evaluate antitumor activity of palbociclib in combination with topotecan and cyclophosphamide in children, adolescents, and young adults with recurrent or refractory neuroblastoma. Phase 2 to learn about the efficacy of palbociclib in combination with irinotecan and temozolomide when compared with irinotecan and temozolomide alone in the treatment of children, adolescents, and young adults with recurrent or refractory Ewing sarcoma (EWS).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tanya Watt
128737
All
2 Years to 20 Years old
Phase 2
NCT03709680
STU-2019-0554
Inclusion:
• Histologically confirmed relapsed or refractory solid tumor as follows:
• For dose escalation and dose determination parts: Histologically confirmed relapsed or refractory solid tumor (including CNS tumors but not lymphomas). Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll.
• For dose expansion and tumor specific cohorts: Histologically confirmed relapsed or refractory solid tumor including but not limited to EWS, rhabdoid tumor, rhabdomyosarcoma, neuroblastoma, and medulloblastoma. Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll. EWS is not eligible for TOPO and CTX tumor-specific cohorts.
• For randomized Phase 2 part: Histologically confirmed Ewing sarcoma at diagnosis or at relapse, with presence of EWSR1-ETS or FUS-ETS rearrangement. Histopathology confirmation of both EWSR1-ETS or FUS-ETS rearrangement partners is required OR availability of formalin fixed paraffin embedded (FFPE) tumor tissue sample for central testing. Patient must have relapsed or have refractory disease and at least evaluable disease in at least one site other than bone marrow that can be followed by imaging.
• Age ≥2 and <21 years at the time of study entry.
• Lansky performance status ≥50% for patients ≤16 years of age, or Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2 for patients >16 years of age.
• Adequate bone marrow function.
• Absolute neutrophil count ≥1000/mm3;
• Platelet count ≥75,000/mm3 (transfusion independent, no platelet transfusion in past 7 days prior study entry);
• Hemoglobin ≥8.5 g/dL (transfusion allowed).
• Adequate renal function: Serum creatinine level based on age/gender must within protocol specified limits.
• Adequate liver function, including:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN) or ≤5 × ULN for age, if attributable to disease involvement of the liver;
• Total bilirubin ≤1.5 × ULN for age, unless the patient has documented Gilbert's syndrome.Patients with documented Gilbert's syndrome are eligible if direct bilirubin is within normal ranges (≤ULN).
• Patients enrolled to Phase 1 portion of the study and tumor specific cohorts must have measurable disease as defined by RECIST version 1.1 or modified RANO criteria for CNS disease or at least evaluable disease by INRC for neuroblastoma. The eligible patients with neuroblastoma must have at least one of the following at the time of study entry:
• Measurable tumor by CT or MRI that is avid on MIBG scan or demonstrates increased FDG uptake on PET scan;
• Avid lesion on MIBG scan with positive uptake at a minimum of one site;
• For disease that is not avid by MIBG-scan, at least one lesion that demonstrates increased FDG uptake on PET scan AND viable neuroblastoma confirmed by current or prior biopsy;
• bone marrow involvement with more than 5% neuroblastoma cells in at least one sample from bilateral bone marrow biopsies;
• In non MIBG-avid refractory soft tissue disease that does not demonstrate increased FDG uptake; lesion biopsy is required to document the presence of viable neuroblastoma, unless patient has a new soft tissue lesion (radiographic evidence of disease progression). Patients with EWS enrolled to Phase 2 portion of the study are eligible with evaluable disease (eg, bone only disease with no soft tissue component).
• Recovered to CTCAE Grade ≤1, or to baseline, from any non-hematological acute toxicities of prior surgery, chemotherapy, immunotherapy, radiotherapy, differentiation therapy or biologic therapy, with the exception of alopecia.
• Serum/urine pregnancy test (for all girls ≥8 years of age) negative at screening and at the baseline visit. Exclusion:
• Phase 1 and tumor specific cohorts: For palbociclib with IRN and TMZ combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with an IRN-containing regimen that includes TMZ. Patients who have received the combination of IRN and TMZ and did not progress while on these medications are eligible. For patients enrolling in the palbociclib with TOPO and CTX combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with a TOPO-containing regimen that includes CTX. Patients who have received the combination of TOPO and CTX and did not progress while on these medications are eligible. Phase 2 portion: prior treatment with a CDK4/6 inhibitor or progression while on treatment with an IRN-containing or TMZ-containing regimen. Patients who have received IRN and/or TMZ and did not progress while on these medications are eligible.
• Prior intolerability to IRN and/or TMZ plus/minus palbociclib with IRN and TMZ combination and prior intolerability to TOPO and/or CTX for TOPO and CTX combination. For patients enrolled in the UK, any contraindication for IRN and/or TMZ treatment, as per the local SmPC.
• Use of strong cytochrome P450 (CYP) 3A inhibitors or inducers within 12 days of study entry. Patients who are receiving strong uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) inhibitors within 12 days of Cycle 1 Day 1 (C1D1) are not eligible for the palbociclib with IRN and TMZ combination. Patients who are receiving strong UGT1A1 inhibitors within 12 days of C1D1 are eligible for the palbociclib with TOPO and CTX combination (See Section 5.7.1 for list of products.)
• Systemic anti cancer therapy within 2 weeks prior to study entry and 6 weeks for nitrosoureas.
• Prior irradiation to >50% of the bone marrow (see Appendix 9).
• Participation in other studies involving investigational drug(s) within 2 weeks or 5 half lives, whichever is longer, prior to study entry.
• Major surgery within 4 weeks prior to study entry. Surgical biopsies or central line placement are not considered major surgeries.
• For IRN and TMZ with/without palbociclib combinations: known or suspected hypersensitivity to palbociclib, dacarbazine, IRN and/or TMZ. For combination of palbociclib with TOPO and CTX: known or suspected hypersensitivity to palbociclib, TOPO and/or CTX.
• Patients with known symptomatic brain tumors or brain metastases and require steroids, unless they have been on a stable or on a decreasing steroid dose for >14 days.
• Patients with previously diagnosed brain metastases are eligible if they have completed their prior treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry for these metastases for at least 14 days post radiation and 4 weeks post-surgery and are neurologically stable.
• Hereditary bone marrow failure disorder.
• QTc >470 msec.
• History of clinically significant or uncontrolled cardiac disease, including:
• History of or active congestive heart failure; if patient had congestive heart failure resolve and >1 year from resolution, patient will be considered eligible;
• Clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation or Torsades de Pointes);
• Diagnosed or suspected congenital or acquired prolonged QT syndrome;
• Need for medications known to prolong the QT interval;
• Uncorrected hypomagnesemia or hypokalemia because of potential effects on the QT interval;
• Left ventricular ejection fraction <50% or shortening fraction <28%.
• Recent or ongoing clinically significant gastrointestinal disorder that may interfere with absorption of orally administered drugs (eg, gastrectomy).
• Evidence of serious active or uncontrolled bacterial, fungal or viral infection or known history of hepatitis B virus, hepatitis C virus, or human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness. Screening for viral hepatitis and HIV is under discretion of investigator unless required by local regulation.
• Severe acute or chronic medical or laboratory test abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results, and in the judgment of the Investigator, would make the patient inappropriate for entry into this study.
• Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees, including their family members, directly involved in the conduct of the study.
• Fertile male patients or female patients of childbearing potential who are unwilling or unable to follow contraceptive requirements.
• Pregnant or breastfeeding women.
• Histologically confirmed relapsed or refractory solid tumor as follows:
• For dose escalation and dose determination parts: Histologically confirmed relapsed or refractory solid tumor (including CNS tumors but not lymphomas). Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll.
• For dose expansion and tumor specific cohorts: Histologically confirmed relapsed or refractory solid tumor including but not limited to EWS, rhabdoid tumor, rhabdomyosarcoma, neuroblastoma, and medulloblastoma. Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll. EWS is not eligible for TOPO and CTX tumor-specific cohorts.
• For randomized Phase 2 part: Histologically confirmed Ewing sarcoma at diagnosis or at relapse, with presence of EWSR1-ETS or FUS-ETS rearrangement. Histopathology confirmation of both EWSR1-ETS or FUS-ETS rearrangement partners is required OR availability of formalin fixed paraffin embedded (FFPE) tumor tissue sample for central testing. Patient must have relapsed or have refractory disease and at least evaluable disease in at least one site other than bone marrow that can be followed by imaging.
• Age ≥2 and <21 years at the time of study entry.
• Lansky performance status ≥50% for patients ≤16 years of age, or Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2 for patients >16 years of age.
• Adequate bone marrow function.
• Absolute neutrophil count ≥1000/mm3;
• Platelet count ≥75,000/mm3 (transfusion independent, no platelet transfusion in past 7 days prior study entry);
• Hemoglobin ≥8.5 g/dL (transfusion allowed).
• Adequate renal function: Serum creatinine level based on age/gender must within protocol specified limits.
• Adequate liver function, including:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN) or ≤5 × ULN for age, if attributable to disease involvement of the liver;
• Total bilirubin ≤1.5 × ULN for age, unless the patient has documented Gilbert's syndrome.Patients with documented Gilbert's syndrome are eligible if direct bilirubin is within normal ranges (≤ULN).
• Patients enrolled to Phase 1 portion of the study and tumor specific cohorts must have measurable disease as defined by RECIST version 1.1 or modified RANO criteria for CNS disease or at least evaluable disease by INRC for neuroblastoma. The eligible patients with neuroblastoma must have at least one of the following at the time of study entry:
• Measurable tumor by CT or MRI that is avid on MIBG scan or demonstrates increased FDG uptake on PET scan;
• Avid lesion on MIBG scan with positive uptake at a minimum of one site;
• For disease that is not avid by MIBG-scan, at least one lesion that demonstrates increased FDG uptake on PET scan AND viable neuroblastoma confirmed by current or prior biopsy;
• bone marrow involvement with more than 5% neuroblastoma cells in at least one sample from bilateral bone marrow biopsies;
• In non MIBG-avid refractory soft tissue disease that does not demonstrate increased FDG uptake; lesion biopsy is required to document the presence of viable neuroblastoma, unless patient has a new soft tissue lesion (radiographic evidence of disease progression). Patients with EWS enrolled to Phase 2 portion of the study are eligible with evaluable disease (eg, bone only disease with no soft tissue component).
• Recovered to CTCAE Grade ≤1, or to baseline, from any non-hematological acute toxicities of prior surgery, chemotherapy, immunotherapy, radiotherapy, differentiation therapy or biologic therapy, with the exception of alopecia.
• Serum/urine pregnancy test (for all girls ≥8 years of age) negative at screening and at the baseline visit. Exclusion:
• Phase 1 and tumor specific cohorts: For palbociclib with IRN and TMZ combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with an IRN-containing regimen that includes TMZ. Patients who have received the combination of IRN and TMZ and did not progress while on these medications are eligible. For patients enrolling in the palbociclib with TOPO and CTX combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with a TOPO-containing regimen that includes CTX. Patients who have received the combination of TOPO and CTX and did not progress while on these medications are eligible. Phase 2 portion: prior treatment with a CDK4/6 inhibitor or progression while on treatment with an IRN-containing or TMZ-containing regimen. Patients who have received IRN and/or TMZ and did not progress while on these medications are eligible.
• Prior intolerability to IRN and/or TMZ plus/minus palbociclib with IRN and TMZ combination and prior intolerability to TOPO and/or CTX for TOPO and CTX combination. For patients enrolled in the UK, any contraindication for IRN and/or TMZ treatment, as per the local SmPC.
• Use of strong cytochrome P450 (CYP) 3A inhibitors or inducers within 12 days of study entry. Patients who are receiving strong uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) inhibitors within 12 days of Cycle 1 Day 1 (C1D1) are not eligible for the palbociclib with IRN and TMZ combination. Patients who are receiving strong UGT1A1 inhibitors within 12 days of C1D1 are eligible for the palbociclib with TOPO and CTX combination (See Section 5.7.1 for list of products.)
• Systemic anti cancer therapy within 2 weeks prior to study entry and 6 weeks for nitrosoureas.
• Prior irradiation to >50% of the bone marrow (see Appendix 9).
• Participation in other studies involving investigational drug(s) within 2 weeks or 5 half lives, whichever is longer, prior to study entry.
• Major surgery within 4 weeks prior to study entry. Surgical biopsies or central line placement are not considered major surgeries.
• For IRN and TMZ with/without palbociclib combinations: known or suspected hypersensitivity to palbociclib, dacarbazine, IRN and/or TMZ. For combination of palbociclib with TOPO and CTX: known or suspected hypersensitivity to palbociclib, TOPO and/or CTX.
• Patients with known symptomatic brain tumors or brain metastases and require steroids, unless they have been on a stable or on a decreasing steroid dose for >14 days.
• Patients with previously diagnosed brain metastases are eligible if they have completed their prior treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry for these metastases for at least 14 days post radiation and 4 weeks post-surgery and are neurologically stable.
• Hereditary bone marrow failure disorder.
• QTc >470 msec.
• History of clinically significant or uncontrolled cardiac disease, including:
• History of or active congestive heart failure; if patient had congestive heart failure resolve and >1 year from resolution, patient will be considered eligible;
• Clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation or Torsades de Pointes);
• Diagnosed or suspected congenital or acquired prolonged QT syndrome;
• Need for medications known to prolong the QT interval;
• Uncorrected hypomagnesemia or hypokalemia because of potential effects on the QT interval;
• Left ventricular ejection fraction <50% or shortening fraction <28%.
• Recent or ongoing clinically significant gastrointestinal disorder that may interfere with absorption of orally administered drugs (eg, gastrectomy).
• Evidence of serious active or uncontrolled bacterial, fungal or viral infection or known history of hepatitis B virus, hepatitis C virus, or human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness. Screening for viral hepatitis and HIV is under discretion of investigator unless required by local regulation.
• Severe acute or chronic medical or laboratory test abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results, and in the judgment of the Investigator, would make the patient inappropriate for entry into this study.
• Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees, including their family members, directly involved in the conduct of the study.
• Fertile male patients or female patients of childbearing potential who are unwilling or unable to follow contraceptive requirements.
• Pregnant or breastfeeding women.
Drug: Palbociclib, Drug: Temozolomide, Drug: Irinotecan, Drug: Topotecan, Drug: Cyclophosphamide
Neuroblastoma, Sarcoma, Solid Tumors, Ewing Sarcoma, Medulloblastoma, Diffuse Intrinsic Pontine Glioma, Rhabdomyosarcoma, Rhabdoid Tumor, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Kaposis sarcoma, Small Intestine, Soft Tissue, Ill - Defined Sites
Ewing Sarcoma, EWS, Neuroblastoma, Recurrent Neuroblastoma, Solid Tumor, Recurrent Solid Tumors, Refractory Solid Tumors, Bone Cancer, Bone Tumor, Bone Sarcoma, Soft Tissue Cancer, Soft Tissue Sarcoma, Recurrent Ewing Sarcoma, Refractory Ewing Sarcoma, Relapsed Ewing Sarcoma, Pediatric Cancer, Childhood Cancer, Ewing Sarcoma Treatment, Palbociclib, CDK4/6 Inhibitor, Irinotecan, Temozolomide, Topotecan, Cyclophosphamide
Children’s Health
A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001) (LIBRETTO-001)
This is an open-label, first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of selpercatinib (also known as LOXO-292) administered orally to participants with advanced solid tumors, including rearranged during transfection (RET)-fusion-positive solid tumors, medullary thyroid cancer (MTC) and other tumors with RET activation.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
206021
All
12 Years and over
Phase 1/Phase 2
NCT03157128
STU 082018-008
Key
• Participants with a locally advanced or metastatic solid tumor that:
• Has progressed on or is intolerant to standard therapy, or
• For which no standard therapy exists, or in the opinion of the Investigator, are not candidates for or would be unlikely to tolerate or derive significant clinical benefit from standard therapy, or
• Decline standard therapy
• Prior multikinase inhibitors (MKIs) with anti-RET activity are allowed
• A RET gene alteration is not required initially. Once adequate PK exposure is achieved, evidence of RET gene alteration in tumor and/or blood is required as identified through molecular assays, as performed for clinical evaluation
• Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as appropriate to tumor type
• Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 or Lansky Performance Score (LPS) greater than or equal to (≥) 40 percent (%) (age less than [<] 16 years) with no sudden deterioration 2 weeks prior to the first dose of study treatment
• Adequate hematologic, hepatic and renal function
• Life expectancy of at least 3 months For Phase 2: As for phase 1 with the following modifications:
• For Cohort 1: Participants must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinical benefit from appropriate standard of care therapy
• Cohorts 1 and 2:
• Enrollment will be restricted to participants with evidence of a RET gene alteration in tumor
• At least one measurable lesion as defined by RECIST 1.1 or RANO, as appropriate to tumor type and not previously irradiated
• Cohorts 3 and 4: Enrollment closed
• Cohort 5:
• Cohorts 1-4 without measurable disease
• MCT not meeting the requirements for Cohorts 3 or 4
• MTC syndrome spectrum cancers (e.g., MTC, pheochromocytoma), cancers with neuroendocrine features/differentiation, or poorly differentiated thyroid cancers with other RET alteration/activation may be allowed with prior Sponsor approval
• cfDNA positive for a RET gene alteration not known to be present in a tumor sample
• Cohort 6: Participants who otherwise are eligible for Cohorts 1, 2 or 5 who discontinued another RET inhibitor may be eligible with prior Sponsor approval
• Cohort 7: Participants with a histologically confirmed stage IB-IIIA NSCLC and a RET fusion; determined to be medically operable and tumor deemed resectable by a thoracic surgical oncologist, without prior systemic treatment for NSCLC Key Exclusion Criteria (Phase 1 and Phase 2):
• Phase 2 Cohorts 1 and 2: an additional known oncogenic driver
• Cohorts 3 and 4: Enrollment closed
• Cohorts 1, 2 and 5: prior treatment with a selective RET inhibitor Notes: Participants otherwise eligible for Cohorts 1, 2, and 5 who discontinued another selective RET inhibitor may be eligible for Phase 2 Cohort 6 with prior Sponsor approval
• Investigational agent or anticancer therapy (including chemotherapy, biologic therapy, immunotherapy, anticancer Chinese medicine or other anticancer herbal remedy) within 5 half-lives or 2 weeks (whichever is shorter) prior to planned start of LOXO-292 (selpercatinib). In addition, no concurrent investigational anti-cancer therapy is permitted Note: Potential exception for this exclusion criterion will require a valid scientific justification and approval from the Sponsor
• Major surgery (excluding placement of vascular access) within 2 weeks prior to planned start of LOXO-292 (selpercatinib)
• Radiotherapy with a limited field of radiation for palliation within 1 week of planned start of LOXO-292 (selpercatinib), with the exception of participants receiving radiation to more than 30% of the bone marrow or with a wide field of radiation, which must be completed at least 4 weeks prior to the first dose of study treatment
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy
• Symptomatic primary CNS tumor, metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression. Participants are eligible if neurological symptoms and CNS imaging are stable and steroid dose is stable for 14 days prior to the first dose of LOXO-292 (selpercatinib) and no CNS surgery or radiation has been performed for 28 days, 14 days if stereotactic radiosurgery (SRS)
• Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-292 (selpercatinib) or prolongation of the QT interval corrected (QTcF) greater than (>) 470 milliseconds (msec)
• Participants with implanted pacemakers may enter the study without meeting QTc criteria due to nonevaluable measurement if it is possible to monitor for QT changes.
• Participants with bundle branch block may be considered for study entry if QTc is appropriate by a formula other than Fridericia's and if it is possible to monitor for QT changes.
• Required treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and certain prohibited concomitant medications
• Phase 2 Cohort 7 (neoadjuvant treatment): Participant must not have received prior systemic therapy for NSCLC.
Inclusion Criteria:
For Phase 1:
• Participants with a locally advanced or metastatic solid tumor that:
• Has progressed on or is intolerant to standard therapy, or
• For which no standard therapy exists, or in the opinion of the Investigator, are not candidates for or would be unlikely to tolerate or derive significant clinical benefit from standard therapy, or
• Decline standard therapy
• Prior multikinase inhibitors (MKIs) with anti-RET activity are allowed
• A RET gene alteration is not required initially. Once adequate PK exposure is achieved, evidence of RET gene alteration in tumor and/or blood is required as identified through molecular assays, as performed for clinical evaluation
• Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as appropriate to tumor type
• Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 or Lansky Performance Score (LPS) greater than or equal to (≥) 40 percent (%) (age less than [<] 16 years) with no sudden deterioration 2 weeks prior to the first dose of study treatment
• Adequate hematologic, hepatic and renal function
• Life expectancy of at least 3 months For Phase 2: As for phase 1 with the following modifications:
• For Cohort 1: Participants must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinical benefit from appropriate standard of care therapy
• Cohorts 1 and 2:
• Enrollment will be restricted to participants with evidence of a RET gene alteration in tumor
• At least one measurable lesion as defined by RECIST 1.1 or RANO, as appropriate to tumor type and not previously irradiated
• Cohorts 3 and 4: Enrollment closed
• Cohort 5:
• Cohorts 1-4 without measurable disease
• MCT not meeting the requirements for Cohorts 3 or 4
• MTC syndrome spectrum cancers (e.g., MTC, pheochromocytoma), cancers with neuroendocrine features/differentiation, or poorly differentiated thyroid cancers with other RET alteration/activation may be allowed with prior Sponsor approval
• cfDNA positive for a RET gene alteration not known to be present in a tumor sample
• Cohort 6: Participants who otherwise are eligible for Cohorts 1, 2 or 5 who discontinued another RET inhibitor may be eligible with prior Sponsor approval
• Cohort 7: Participants with a histologically confirmed stage IB-IIIA NSCLC and a RET fusion; determined to be medically operable and tumor deemed resectable by a thoracic surgical oncologist, without prior systemic treatment for NSCLC Key Exclusion Criteria (Phase 1 and Phase 2):
• Phase 2 Cohorts 1 and 2: an additional known oncogenic driver
• Cohorts 3 and 4: Enrollment closed
• Cohorts 1, 2 and 5: prior treatment with a selective RET inhibitor Notes: Participants otherwise eligible for Cohorts 1, 2, and 5 who discontinued another selective RET inhibitor may be eligible for Phase 2 Cohort 6 with prior Sponsor approval
• Investigational agent or anticancer therapy (including chemotherapy, biologic therapy, immunotherapy, anticancer Chinese medicine or other anticancer herbal remedy) within 5 half-lives or 2 weeks (whichever is shorter) prior to planned start of LOXO-292 (selpercatinib). In addition, no concurrent investigational anti-cancer therapy is permitted Note: Potential exception for this exclusion criterion will require a valid scientific justification and approval from the Sponsor
• Major surgery (excluding placement of vascular access) within 2 weeks prior to planned start of LOXO-292 (selpercatinib)
• Radiotherapy with a limited field of radiation for palliation within 1 week of planned start of LOXO-292 (selpercatinib), with the exception of participants receiving radiation to more than 30% of the bone marrow or with a wide field of radiation, which must be completed at least 4 weeks prior to the first dose of study treatment
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy
• Symptomatic primary CNS tumor, metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression. Participants are eligible if neurological symptoms and CNS imaging are stable and steroid dose is stable for 14 days prior to the first dose of LOXO-292 (selpercatinib) and no CNS surgery or radiation has been performed for 28 days, 14 days if stereotactic radiosurgery (SRS)
• Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-292 (selpercatinib) or prolongation of the QT interval corrected (QTcF) greater than (>) 470 milliseconds (msec)
• Participants with implanted pacemakers may enter the study without meeting QTc criteria due to nonevaluable measurement if it is possible to monitor for QT changes.
• Participants with bundle branch block may be considered for study entry if QTc is appropriate by a formula other than Fridericia's and if it is possible to monitor for QT changes.
• Required treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and certain prohibited concomitant medications
• Phase 2 Cohort 7 (neoadjuvant treatment): Participant must not have received prior systemic therapy for NSCLC.
Drug: LOXO-292
Lymphoma, Non-Small Cell Lung Cancer, Colon Cancer, Medullary Thyroid Cancer, Any Solid Tumor, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Stomach, Thyroid, Urinary Bladder, Hodgkins Lymphoma, Small Intestine, Soft Tissue
LOXO-292, KIF5B-RET, M918T, CCDC6-RET, RET-PTC1, NCOA4-RET, RET-PTC, RET-PTC3, RET-PTC4, PRKAR1A-RET, RET-PTC2, GOLGA5-RET, RET-PTC5, ERC1-RET, KTN1-RET, RET-PTC8, HOOK3-RET, PCM1-RET, TRIM24-RET, RET-PTC6, TRIM27-RET, TRIM33-RET, RET-PTC7, AKAP13-RET, FKBP15-RET, SPECC1L-RET, TBL1XR1-RET, BCR-RET, FGRF1OP-RET, RFG8-RET, RET-PTC9, ACBD5-RET, MYH13-RET, CUX1-RET, KIAA1468-RET, FRMD4A-RET, SQSTM1-RET, AFAP1L2-RET, PPFIBP2-RET, EML4-RET, PARD3-RET, G533C, C609F, C609G, C609R, C609S, C609Y, C611F, C611G, C611S, C611Y, C611W, C618F, C618R, C618S, C620F, C620R, C620S, C630R, C630Y, D631Y, C634F, C634G, C634R, C634S, C634W, C634Y, K666E, E768D, L790F, V804L, V804M, A883F, S891A, R912P, CLIP1-RET, Y806C, RET fusion, RET alteration, RET mutation, RET rearrangement, RET translocation, Neoplasms by Site, Neoplasms, Non-Small Cell Lung Cancer, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Cancer of Lung, Cancer of the Lung, Lung Cancer, Neoplasms, Lung, Neoplasms, Pulmonary, Pulmonary Cancer, Pulmonary Neoplasms, Respiratory Tract Neoplasms, Lung Diseases, Respiratory Tract Diseases, Carcinoma, Bronchogenic, Bronchial Neoplasms, Medullary Thyroid Cancer, Papillary Thyroid Cancer, Thyroid Diseases, Thyroid Neoplasms, Cancer of the Thyroid, Cancer of Thyroid, Neoplasms, Thyroid, Thyroid Ademona, Thyroid Cancer, Thyroid Carcinoma, Endocrine System Diseases, Endocrine Gland Neoplasms, Head and Neck Neoplasms, Thoracic Neoplasms, CNS tumor, Primary CNS tumor, Cancer of Colon, Cancer of the Colon, Colon Cancer, Colon Neoplasms, Colonic Cancer, Neoplasms, Colonic, Malignant tumor of Breast, Mammary Cancer, Mammary Carcinoma, Human, Mammary Neoplasm, Human, Neoplasms, Breast, Tumors, Breast, Human Mammary Carcinoma, Malignant Neoplasm of Breast, Breast Carcinoma, Breast Tumors, Cancer of the Breast, Breast Neoplasms, Breast Cancer, RET Inhibitor, MTC, NSCLC, selpercatinib, neo-adjuvant treatment in early stage NSCLC
UT Southwestern
Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
This Pediatric MATCH screening and multi-sub-study phase II trial studies how well treatment that is directed by genetic testing works in pediatric patients with solid tumors, non-Hodgkin lymphomas, or histiocytic disorders that have progressed following at least one line of standard systemic therapy and/or for which no standard treatment exists that has been shown to prolong survival. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic changes or abnormalities (mutations) may benefit more from treatment which targets their tumor's particular genetic mutation, and may help doctors plan better treatment for patients with solid tumors or non-Hodgkin lymphomas.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Avanthi Shah
74989
All
12 Months to 21 Years old
Phase 2
NCT03155620
STU 072017-080
Inclusion Criteria:
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must be >= 12 months and =< 21 years of age at the time of study enrollment
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients with recurrent or refractory solid tumors, including non-Hodgkin lymphomas, histiocytoses (e.g. langerhans cell histiocytosis [LCH], juvenile xanthogranuloma [JXG], histiocytic sarcoma), and central nervous system (CNS) tumors are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG); in cases where patient enrolls prior to histologic confirmation of recurrent disease, patient is ineligible and should be withdrawn from study if histology fails to confirm recurrence; please note: Patients with Hodgkin lymphoma and plexiform neurofibroma are not eligible
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor Testing Requirement: Tumor sample availability requirement for stage 1 of Pediatric MATCH (patients enrolled from start of study in July 2017 through 12/31/21); Patients must have an formalin-fixed paraffin-embedded (FFPE) tumor sample available for MATCH study testing from a biopsy or surgery that was performed at any point after initial tumor recurrence/progression, or be planned to have a procedure to obtain such a sample that is considered to be of potential benefit by the treating clinicians; a tumor sample from a clinically performed diagnostic (pre-treatment) biopsy will be acceptable for enrollment onto Pediatric MATCH only for children with high-grade gliomas of the brainstem (diffuse intrinsic pontine gliomas) or thalamus
• Please note: Samples that have been decalcified using standardly utilized acid-based decalcification methods are not generally suitable for MATCH study testing; the nucleic acids will have been degraded in the decalcification process
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor molecular profiling report availability requirement for Stage 2 of Pediatric MATCH (patients enrolled starting 2022): In stage 2 of the study, no tumor samples will be submitted for centralized clinical tumor profiling; instead, a tumor molecular profiling report from a College of American Pathologists (CAP)/ Clinical Laboratory Improvements Amendments (CLIA)-approved testing laboratory must be submitted for review by the Molecular Review Committee (MRC)
• This molecular profiling must have been performed on a tumor sample that was obtained at any point after initial tumor recurrence/progression and must be accompanied by a pathology report for the same tumor specimen; a molecular profiling report for a diagnostic (pre-treatment) tumor sample will be acceptable for enrollment onto Pediatric MATCH only for children with high-grade gliomas of the brainstem (diffuse intrinsic pontine gliomas) or thalamus. In the event that molecular profiling reports are available from multiple timepoints, the most recent report should be prioritized for study submission
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age); note: neurologic deficits in patients with central nervous system (CNS) tumors must have been stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must have radiographically measurable disease; measurable disease based on imaging obtained less than or equal to 56 days prior to enrollment; patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (MIBG) positive (+) evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard magnetic resonance imaging (MRI) or computed tomography (CT)
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or CSF
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: NOTE: patient does not need to meet all subprotocol criteria at time of enrollment onto the APEC1621SC screening protocol, but will need to meet all criteria prior to enrollment on any assigned treatment subprotocol. Patients must be enrolled onto a subprotocol within 2 weeks (14 days) of treatment assignment
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age); Note: neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of treatment with subprotocol specified therapy, the patients must have radiographically measurable disease; patients with neuroblastoma who do not have measurable disease but have MIBG+ evaluable are eligible; measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard MRI or CT
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or CSF
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for RECIST 1.1
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of enrollment onto a subprotocol, the following general criteria for initiation of therapy will be required:
• Patients must have fully recovered from the acute toxic effects of all prior anticancer therapy and must meet the following minimum duration from prior anticancer directed therapy prior to enrollment to the subprotocol; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anticancer agents known to be myelosuppressive: for agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anticancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil counts [ANC]): >= 7 days after the last dose of agent; for agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
• Stem cell infusions (with or without total-body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer (NK) cells, dendritic cells, etc.)
• X-ray therapy (XRT)/External Beam Irradiation including Protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation; note: radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: For patients with solid tumors without known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• Age: 1 to < 2 years; maximum serum creatinine (mg/dL): male 0.6; female 0.6
• Age: 2 to < 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8
• Age: 6 to < 10 years; maximum serum creatinine (mg/dL): male 1; female 1
• Age: 10 to < 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2
• Age: 13 to < 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4
• Age: >= 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Serum glutamate pyruvate transaminase (SGPT) (alanine transferase [ALT]) =< 135 U/L (for the purpose of this study, the ULN for SGPT is 45 U/L)
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients must be able to swallow intact capsules/tablets, unless otherwise specified in the subprotocol to which they are assigned
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Agent specific limitations on prior therapy will be included with specific treatment subprotocols
Exclusion Criteria:
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, or because there is currently no available information regarding human fetal or teratogenic toxicities; pregnancy tests must be obtained in females who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Concomitant medications
• Corticosteroids: at the time of consent and enrollment to regimen specific subprotocols, patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment to the subprotocol will not be eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: patients must meet criteria for prior therapy at the time of consent and enrollment to a subprotocol; other investigational agents may not be administered to patients while they are receiving study drug as part of a subprotocol
• Anticancer agents: patients must meet criteria for prior therapy at the time of consent and enrollment to a subprotocol; other investigational agents may not be administered to patients while they are receiving study drug as part of a subprotocol
• Anti-GVHD agents post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have an uncontrolled infection are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have had a prior solid organ transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Additional agent specific criteria will be included with specific treatment subprotocols
Procedure: Biopsy, Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration and Biopsy, Procedure: Bone Scan, Procedure: Computed Tomography, Drug: Ensartinib, Drug: Erdafitinib, Other: Laboratory Biomarker Analysis, Drug: Larotrectinib Sulfate, Procedure: Magnetic Resonance Imaging, Procedure: Mutation Carrier Screening, Drug: Olaparib, Drug: Palbociclib, Other: Pharmacological Study, Procedure: Positron Emission Tomography, Procedure: Radionuclide Imaging, Drug: Samotolisib, Drug: Selpercatinib, Drug: Selumetinib Sulfate, Drug: Tazemetostat, Drug: Tipifarnib, Drug: Ulixertinib, Drug: Vemurafenib, Procedure: X-Ray Imaging
Recurrent Childhood Rhabdomyosarcoma, Sarcoma, Recurrent Neuroblastoma, Malignant Glioma, Recurrent Osteosarcoma, Recurrent Malignant Solid Neoplasm, Advanced Malignant Solid Neoplasm, Recurrent Ewing Sarcoma, Recurrent Hepatoblastoma, Wilms Tumor, Recurrent Glioma, Refractory Malignant Solid Neoplasm, Stage III Soft Tissue Sarcoma AJCC v7, Stage IV Soft Tissue Sarcoma AJCC v7, Histiocytic Sarcoma, Juvenile Xanthogranuloma, Recurrent Langerhans Cell Histiocytosis, Recurrent Peripheral Primitive Neuroectodermal Tumor, Refractory Langerhans Cell Histiocytosis, Refractory Neuroblastoma, Rhabdoid Tumor, Stage III Osteosarcoma AJCC v7, Stage IV Osteosarcoma AJCC v7, Stage IVA Osteosarcoma AJCC v7, Stage IVB Osteosarcoma AJCC v7, Refractory Non-Hodgkin Lymphoma, Recurrent Medulloblastoma, Recurrent Non-Hodgkin Lymphoma, Refractory Malignant Germ Cell Tumor, Langerhans Cell Histiocytosis, Recurrent Rhabdoid Tumor, Recurrent Soft Tissue Sarcoma, Refractory Medulloblastoma, Refractory Osteosarcoma, Refractory Peripheral Primitive Neuroectodermal Tumor, Refractory Rhabdoid Tumor, Recurrent Malignant Germ Cell Tumor, Ann Arbor Stage III Non-Hodgkin Lymphoma, Ann Arbor Stage IV Non-Hodgkin Lymphoma, Refractory Ewing Sarcoma, Refractory Glioma, Refractory Hepatoblastoma, Refractory Rhabdomyosarcoma, Recurrent Ependymoma, Refractory Primary Central Nervous System Neoplasm, Recurrent Primary Central Nervous System Neoplasm, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Non-Hodgkins Lymphoma, Small Intestine, Soft Tissue
Children’s Health
Cutaneous Lupus Registry
Approximately 1.4 million individuals in the United States have systemic lupus erythematosus, and about 85% of these individuals develop skin lesions at some point of their disease. Cutaneous lupus erythematosus represents the skin manifestations of systemic lupus erythematosus, and can appear in people with or without systemic lupus. It is a mentally, physically, and emotionally debilitating disease that affects both the quality of life and social well-being of those affected. The cause of cutaneous lupus is not completely understood, but likely includes multiple factors from our genes and the environment. Multiple genetic studies with small numbers of cutaneous lupus patients have been performed to determine which genes are associated with cutaneous lupus. This study aims to accumulate even larger numbers of patients to confidently identify genes and the proteins they encode that could contribute greatly to the formation of cutaneous lupus. The discovery of these genes and proteins would help not only uncover how cutaneous lupus forms, but also improve our abilities to diagnose this disease and predict its course, and stimulate new drug development.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Tyler.Cepica@UTSouthwestern.edu
Benjamin Chong
99998
All
18 Years and over
N/A
NCT01266915
STU 082010-241
Inclusion Criteria:
• Diagnosed with cutaneous lupus erythematosus and/or systemic lupus erythematosus by clinical, laboratory, and histopathological findings
• Ability to speak and read English or Spanish at a 6th grade reading level (a translator will be available with additional consent forms in Spanish)
• Ability to give written informed consent
Exclusion Criteria:
• Less than 18 years of age, since the characteristics of the disease in these subjects could be very different
• Due to a medication, in which its discontinuation results in the resolution of cutaneous lupus, since the characteristics of the disease in these subjects could be very different
• Medical conditions who do not warrant a skin biopsy
• Unable to give written, informed consent or undergo a skin biopsy and/or venipuncture for any other reason
Lupus Erythematosus, Other Skin
SCLE, CLE, DLE
UT Southwestern
Stereotactic Radiosurgery (SRS) Dose-Escalation Study for Brain Metastasis (SRS)
SRS dose escalation for brain metastases in radiation-naïve patients will establish true tolerable doses, which may exceed the current standard doses. This may lead to an improvement in local control, patient survival, and/or quality-of life.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Robert Timmerman
69821
All
18 Years and over
N/A
NCT02645487
STU 022015-106
Inclusion Criteria
• Biopsy-proven non-hematopoietic malignancy, except for small cell lung cancer, germ cell cancer, or unknown primary tumor.
• Radiographic evidence by MRI (or by CT scan with CT contrast if ineligible or intolerant of MRI) of brain metastasis. (If patient is unable to tolerate MRI contrast, an MRI without contrast is acceptable if lesions are visible)
• All brain metastases must be outside the brain stem (midbrain, pons and medulla).
• Patient must have 10 or less brain metastases.
• The maximum diameter of any lesion must be less than or equal to 3.0 cm.
• Previous treatment with surgery, radiation, chemotherapy, immunotherapy or any targeted agents are allowed provided that:
• Radiation was not to the brain.
• Surgery to the brain was > 7 days prior to SRS and there remains at least one additional brain metastasis that can be targeted with SRS
• Age ≥ 18 years.
• ECOG Performance Score of 2 or better/Karnofsky Performance Status score of 50-60 or better.
• All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). Medically acceptable birth control (contraceptives) includes:
• Approved hormonal contraceptives (such as birth control pills, patch, or ring: Depo-Provera, Implanon), or
• Barrier methods (such as a condom or diaphragm) used with a spermicide (a substance that kills sperm)
• Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria
• Patients had craniotomy and surgery to the brain within 7 days from the date of SRS.
• Patients with leptomeningeal metastasis. NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive CSF cytology and/or equivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology, unless a parenchymal lesion can adequately explain the neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion.
• Patients with a contraindication to both MRI (with or without contrast) and CT scan (with contrast)
• Patients with life expectancy < 3 months.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing at the time of SRS treatment due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Biopsy-proven non-hematopoietic malignancy, except for small cell lung cancer, germ cell cancer, or unknown primary tumor.
• Radiographic evidence by MRI (or by CT scan with CT contrast if ineligible or intolerant of MRI) of brain metastasis. (If patient is unable to tolerate MRI contrast, an MRI without contrast is acceptable if lesions are visible)
• All brain metastases must be outside the brain stem (midbrain, pons and medulla).
• Patient must have 10 or less brain metastases.
• The maximum diameter of any lesion must be less than or equal to 3.0 cm.
• Previous treatment with surgery, radiation, chemotherapy, immunotherapy or any targeted agents are allowed provided that:
• Radiation was not to the brain.
• Surgery to the brain was > 7 days prior to SRS and there remains at least one additional brain metastasis that can be targeted with SRS
• Age ≥ 18 years.
• ECOG Performance Score of 2 or better/Karnofsky Performance Status score of 50-60 or better.
• All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). Medically acceptable birth control (contraceptives) includes:
• Approved hormonal contraceptives (such as birth control pills, patch, or ring: Depo-Provera, Implanon), or
• Barrier methods (such as a condom or diaphragm) used with a spermicide (a substance that kills sperm)
• Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria
• Patients had craniotomy and surgery to the brain within 7 days from the date of SRS.
• Patients with leptomeningeal metastasis. NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive CSF cytology and/or equivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology, unless a parenchymal lesion can adequately explain the neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion.
• Patients with a contraindication to both MRI (with or without contrast) and CT scan (with contrast)
• Patients with life expectancy < 3 months.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing at the time of SRS treatment due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
Radiation: Stereotactic Radiosurgery
Brain Neoplasms, Adult, Malignant, Lymphoma, Sarcoma, Multiple Myeloma, Brain and Nervous System, Other, Eye and Orbit, Anklylosing Spondylitis, Anus, Bones and Joints, Breast - Female, Breast - Male, Cardiovascular, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Hodgkins Lymphoma, Lymphoid Leukemia, Small Intestine, Soft Tissue
UT Southwestern; Parkland Health & Hospital System
Morphea in Adults and Children (MAC) Cohort Study: A Morphea Registry and DNA Repository (MAC)
The Morphea in Adults and Children (MAC) cohort is the first registry for both children and adults with morphea (also known as localized scleroderma) in the country. The purpose of the registry is to learn more about morphea, specifically: - How morphea behaves over time - How frequently specific problems occur along with morphea (for example, arthritis) - Whether morphea has an autoimmune background
Call 214-648-5005
studyfinder@utsouthwestern.edu, Aleuna.Lee@UTSouthwestern.edu
Heidi Jacobe
54629
All
up to 90 Years old
N/A
NCT01808937
STU 112010-028
Inclusion Criteria:
• Patient must have a clinical diagnosis of morphea confirmed by the primary investigator and by histopathological examination.
• Ages 0-90 years old
• Children must weigh more than 20 lbs. in order to satisfy Children's Medical Center policy for the maximum amount of blood drawn in a 24 hour period.
• Patient or legal guardian must be able to speak and read at a 6th grade reading level.
• Both male and female patients will be eligible
• All races and ethnic backgrounds will be included
• Relationships to proband: All patients with morphea will be included. A patient's family history will be reviewed and if there is a family history of morphea or systemic sclerosis then we will give the study patient the investigator's contact information and ask the family member to call the study team to answer any questions and enroll them in the study if they choose to do so.
• Ability to give informed consent: Patients must be able to give informed consent or they will give assent with parent or guardian consent as a minor to be a part of the morphea registry.
Exclusion Criteria:
• Patients who have been coded as morphea (701.0), but do not have morphea/localized scleroderma (examples: steroid atrophy, acquired keratoderma, keloids, nephrogenic fibrosing dermopathy, systemic sclerosis, lichen sclerosis)
Other: Morphea
Scleroderma, Localized, Morphea, Scleroderma, Circumscribed, Frontal Linear Scleroderma en Coup de Sabre, Scleroderma, Linear, Other Skin
Children’s Health
A Study of Pembrolizumab (MK-3475) in Pediatric Participants With an Advanced Solid Tumor or Lymphoma (MK-3475-051/KEYNOTE-051)
This is a two-part study of pembrolizumab (MK-3475) in pediatric participants who have any of the following types of cancer: - advanced melanoma (6 months to <18 years of age), - advanced, relapsed or refractory programmed death-ligand 1 (PD-L1)-positive malignant solid tumor or other lymphoma (6 months to <18 years of age), - relapsed or refractory classical Hodgkin lymphoma (rrcHL) (3 years to <18 years of age), or - advanced relapsed or refractory microsatellite-instability-high (MSI-H) solid tumors (6 months to <18 years of age). Part 1 will find the maximum tolerated dose (MTD)/maximum administered dose (MAD), confirm the dose, and find the recommended Phase 2 dose (RP2D) for pembrolizumab therapy. Part 2 will further evaluate the safety and efficacy at the pediatric RP2D. The primary hypothesis of this study is that intravenous (IV) administration of pembrolizumab to children with either advanced melanoma; a PD-L1 positive advanced, relapsed or refractory solid tumor or other lymphoma; advanced, relapsed or refractory MSI-H solid tumor; or rrcHL, will result in an Objective Response Rate (ORR) greater than 10% for at least one of these types of cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tanya Watt
128737
All
6 Months to 17 Years old
Phase 1/Phase 2
NCT02332668
STU 052016-090
Inclusion Criteria:
• Between 6 months and <18 years of age (or between 3 years and <18 years of age for rrcHL participants) on day of signing informed consent/assent (the first 3 participants dosed in Part 1 are to be ≥ 6 years of age)
• Histologically- or cytologically-documented, locally-advanced, or metastatic solid malignancy or lymphoma that is incurable and has failed prior standard therapy, or for which no standard therapy exists, or for which no standard therapy is considered appropriate
• Any number of prior treatment regimens
• Tissue (or lymph node biopsy for rrcHL participants) available from an archival tissue sample or, if appropriate, a newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
• Advanced melanoma or PD-L1-positive advanced, relapsed, or refractory solid tumor or lymphoma
• Measurable disease based on RECIST 1.1 (Or based on IWG [Cheson, 2007] [i.e., measurement must be >15 mm in longest diameter or >10 mm in short axis] for rrcHL participants)
• Participants with neuroblastoma with only metaiodobenzylguanidine (MIBG)-positive evaluable disease may be enrolled
• Lansky Play Scale ≥50 for participants from 6 months up to and including 16 years of age; or Karnofsky score ≥50 for participants >16 years of age
• Adequate organ function
• Female participants of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication
• Female participants of childbearing potential must be willing to use 2 methods of contraception or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication
• Male participants of reproductive potential must agree to use an adequate method of contraception starting with the first dose of study medication through 120 days after the last dose of study medication
Exclusion Criteria:
• Currently participating and receiving study therapy in, or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the date of allocation/randomization
• Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the date of allocation/randomization
• Prior systemic anti-cancer therapy including investigational agent within 2 weeks prior to study Day 1 or not recovered from adverse events due to a previously administered agent
• Prior radiotherapy within 2 weeks of start of study treatment
• Known additional malignancy that is progressing or requires active treatment with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical carcinoma in situ) with potentially curative therapy, or in situ cervical cancer
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Tumor(s) involving the brain stem
• Severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients
• Active autoimmune disease that has required systemic treatment in past 2 years; replacement therapy (such as thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is acceptable
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Active infection requiring systemic therapy
• Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial through 120 days after the last dose of study medication
• Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-ligand 1 (anti-PD-L1), anti-PD-L2 agent, or any agent directed to another stimulatory or inhibitory T-cell receptor (eg, cytotoxic lymphocyte associated protein-4 [CTLA-4], OX-40, CD137)
• Human immunodeficiency virus (HIV)
• Hepatitis B or C
• Known history of active tuberculosis (TB; Bacillus tuberculosis)
• Received a live vaccine within 30 days of planned start of study medication
• Has undergone solid organ transplant at any time, or prior allogeneic hematopoietic stem cell transplantation within the last 5 years. (Participants who have had an allogeneic hematopoietic transplant >5 years ago are eligible as long as there are no symptoms of Graft Versus Host Disease [GVHD].)
• History or current evidence of any condition, therapy, or laboratory abnormality, or known severe hypersensitivity to any component or analog of the trial treatment, that might confound the results of the trial, or interfere with the participant's participation for the full duration of the study
• Known psychiatric or substance abuse disorders that would interfere with the requirements of the study
Biological: Pembrolizumab
Lymphoma, Melanoma, Classical Hodgkin Lymphoma, Solid Tumor, Microsatellite-instability-high Solid Tumor, Other, Melanoma, skin
PD1, PD-1, PDL1, PD-L1, cHL, MSI-H
Children’s Health
Phase 1 Dose-escalating Study of MM-398 (Irinotecan Sucrosofate Liposome Injection) Plus Intravenous Cyclophosphamide in Recurrent or Refractory Pediatric Solid Tumors
This is a Phase 1 study of the combination of two drugs: MM-398 and Cyclophosphamide. The goal is to find the highest dose of MM-398 that can be given safely when it is used together with the chemotherapy drug Cyclophosphamide.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Patrick Leavey
35610
All
12 Months to 20 Years old
Phase 1
NCT02013336
STU 092013-007
Inclusion Criteria:
• Histologically or cytologically-confirmed Ewing sarcoma, rhabdomyosarcoma, neuroblastoma, or osteosarcoma
• Disease progression after prior therapy in locally advanced or metastatic setting
• Measurable or evaluable disease based on the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria
• Age 12 months to <21 years
• Adequate bone marrow reserves, hepatic function, and renal function
• Recovered from effects of any prior surgery or cancer therapy
• Patients 18 years or older will provide written consent. A parent or legal guardian of a patient <18 years of age will provide informed consent and patients 11 to 18 years of age will provide written assent or as per participating institutional policy.
Exclusion Criteria:
• Clinically significant gastrointestinal disorders
• NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure
• Active infection or unexplained fever
• Known hypersensitivity to any of the components of MM-398 or other liposomal products
• Recent Investigational therapy
• Pregnant or breast feeding; females of child-bearing potential must test negative for pregnancy at the time of enrollment
Drug: MM-398 (Irinotecan Sucrosofate Liposome Injection) plus cyclophosphamide
Neuroblastoma, Sarcoma, Ewing Sarcoma, Mycosis Fungoides, Rhabdomyosarcoma, Osteosarcoma, Recurrent or Refractory Solid Tumors, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Hodgkins Lymphoma, Kaposis sarcoma, Other Hematopoietic, Small Intestine, Soft Tissue
pediatric, MM-398, cyclophosphamide, irinotecan
Children’s Health
Study of INBRX-109 in Conventional Chondrosarcoma
Randomized, blinded, placebo-controlled, Phase 2 study of INBRX-109 in unresectable or metastatic conventional chondrosarcoma patients.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Jade Homsi
175558
All
18 Years and over
Phase 2
NCT04950075
STU-2021-0831
Inclusion Criteria:
• Conventional chondrosarcoma, unresectable (=inoperable) or metastatic.
• Measurable disease by RECISTv1.1. Note: Tumor lesions located in a previously irradiated (or other locally treated) area will be considered measurable, provided there has been clear imaging-based progression of the lesions since the time of treatment.
• Radiologic progression of disease per RECISTv1.1 criteria within 6 months prior to screening for this study.
• Adequate hematologic, coagulation, hepatic and renal function as defined per protocol.
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
• Estimated life expectancy of at least 12 weeks.
• Availability of archival tissue or fresh cancer biopsy are mandatory.
Exclusion Criteria:
• Any prior exposure to DR5 agonists.
• Allergy or sensitivity to INBRX-109 or known allergies to CHO-produced antibodies.
• Non-conventional chondrosarcoma, e.g., clear-cell, mesenchymal, extraskeletal myxoid, myxoid, and dedifferentiated chondrosarcoma.
• Prior or concurrent malignancies. Exception: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessments.
• Chronic liver diseases. Exception: Patients with fatty liver disease are acceptable as long as adequate hepatic function as defined in the inclusion criteria is confirmed.
• Other exclusion criteria per protocol.
Drug: INBRX-109, Drug: Placebo
Other Skin, Conventional Chondrosarcoma
DR5, INBRX-109, Apoptosis, Programmed cell death
UT Southwestern; Parkland Health & Hospital System
A Study of HMBD-002, a Monoclonal Antibody Targeting VISTA, as Monotherapy and Combined With Pembrolizumab
This is a phase 1/2, open-label, multi-center, first-in-human, two-stage (Part 1: dose escalation and Part 2: dose expansion) study evaluating multiple doses and schedules of intravenously (IV) administered HMBD-002, with or without pembrolizumab, in patients with advanced solid tumors (i.e., locally advanced and unresectable, or metastatic).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Joshua Gruber
202745
All
18 Years and over
Phase 1
NCT05082610
STU-2021-1161
Inclusion Criteria (Phase 1 and 2 Stages)
• Histologic or cytologic evidence of a malignant solid cancer (any histology) with advanced or metastatic disease and no available therapies known to confer clinical benefit.
• Tumor tissue, or paraffin block, ideally from the patient's most recent biopsy. A fresh tumor biopsy will be obtained if archival samples are not available.
• Measurable by Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
• At least 18 years old.
• An Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
• Adequate hematopoietic, kidney, and liver functions.
• A left ventricular ejection fraction (LVEF) ≥ 45%.
• Women of childbearing potential (WOCBP) must not be pregnant or breastfeeding. A WOCBP must agree to follow contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.
• Male subjects must agree to follow contraceptive guidance during the study period and for at least 120 days after the last dose of study treatment.
• Patient must give informed written consent for the study. Inclusion Criteria for HMBD-002 Phase 2 Stage Triple Negative Breast Cancer (TNBC)
• Histologic or cytologic evidence of TNBC that is advanced or metastatic.
• Will be requested to undergo a tumor biopsy before treatment and after 6 weeks of treatment.
• Must have received appropriate treatment with at least one prior regimen for TNBC and there are no available therapies known to confer clinical benefit. Non-Small Cell Lung Cancer (Monotherapy and Combination)
• Histologic or cytologic evidence of NSCLC that is advanced or metastatic.
• Will be requested to undergo a tumor biopsy before treatment and after 6 weeks of treatment.
• Absence of an activating mutation of the EGFR or ALK.
• Must have received treatment with an approved therapy if there are other genomic aberrations for which targeted therapies are approved and available.
• Must have had disease progression on at least one approved or comparable standard therapy for NSCLC.
• Must have received appropriate prior treatment with a mAb to PD-1 or PD-L1. Multiple Other Cancers (Combination Therapy Baskets)
• Histologic or cytologic evidence of an advanced or metastatic cancer aside from TNBC and NSCLC with no available therapies known to confer clinical benefit.
• Will be requested to undergo a tumor biopsy before treatment and after 6 weeks of treatment.
• Must have had appropriate treatment for their specific cancer and there is an absence of available therapy with a reasonable likelihood of conferring clinical benefit. Exclusion Criteria
• If the patient received prior therapy with an anti-PD-1 or anti-PD-L1 mAb or with an agent targeting stimulatory or co-inhibitory T-cell receptor and was discontinued from that treatment due to a Grade 3 or higher immune related adverse event.
• Received radiotherapy within 2 weeks of treatment.
• Received radiotherapy exceeding 30 Gray (Gy) to the lung within 6 months of the first dose of study medication.
• Received an allogeneic tissue/solid organ transplant.
• Received a live or live-attenuated vaccine within 30 days prior to the first dose of study medication.
• Received a VISTA targeting agent.
• The patient must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline.
• The patient has an active autoimmune disease that required systemic treatment in the past.
• Presence of an uncontrolled endocrine disorder.
• Presence of clinically significant cardiovascular disease.
• History of (non-infectious) pneumonitis or interstitial pulmonary disease that required steroids or has current pneumonitis or interstitial pulmonary disease.
• Presence of uncontrolled, clinically significant pulmonary disease.
• A previous a severe hypersensitivity reaction (≥ Grade 3) to pembrolizumab and/or any of its excipients.
• A diagnosis of immunodeficiency or is receiving chronic systemic corticosteroids at a dose that exceeds 10 mg daily of prednisone equivalent or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.
• An uncontrolled intercurrent illness that would limit compliance with the study.
• A positive status for human immunodeficiency virus (HIV).
• A known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C viral (defined as HCV RNA detected) infection.
• Oxygen-dependence.
• A medical condition which, in the opinion of the Investigator, places the patient at an unacceptably high risk for toxicity.
• A positive COVID test within one week of study treatment if not fully vaccinated.
• Another active malignancy that is progressing or has required active treatment within the past 3 years.
• Known active central nervous system metastases and/or carcinomatous meningitis.
• Histologic or cytologic evidence of a malignant solid cancer (any histology) with advanced or metastatic disease and no available therapies known to confer clinical benefit.
• Tumor tissue, or paraffin block, ideally from the patient's most recent biopsy. A fresh tumor biopsy will be obtained if archival samples are not available.
• Measurable by Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
• At least 18 years old.
• An Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
• Adequate hematopoietic, kidney, and liver functions.
• A left ventricular ejection fraction (LVEF) ≥ 45%.
• Women of childbearing potential (WOCBP) must not be pregnant or breastfeeding. A WOCBP must agree to follow contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.
• Male subjects must agree to follow contraceptive guidance during the study period and for at least 120 days after the last dose of study treatment.
• Patient must give informed written consent for the study. Inclusion Criteria for HMBD-002 Phase 2 Stage Triple Negative Breast Cancer (TNBC)
• Histologic or cytologic evidence of TNBC that is advanced or metastatic.
• Will be requested to undergo a tumor biopsy before treatment and after 6 weeks of treatment.
• Must have received appropriate treatment with at least one prior regimen for TNBC and there are no available therapies known to confer clinical benefit. Non-Small Cell Lung Cancer (Monotherapy and Combination)
• Histologic or cytologic evidence of NSCLC that is advanced or metastatic.
• Will be requested to undergo a tumor biopsy before treatment and after 6 weeks of treatment.
• Absence of an activating mutation of the EGFR or ALK.
• Must have received treatment with an approved therapy if there are other genomic aberrations for which targeted therapies are approved and available.
• Must have had disease progression on at least one approved or comparable standard therapy for NSCLC.
• Must have received appropriate prior treatment with a mAb to PD-1 or PD-L1. Multiple Other Cancers (Combination Therapy Baskets)
• Histologic or cytologic evidence of an advanced or metastatic cancer aside from TNBC and NSCLC with no available therapies known to confer clinical benefit.
• Will be requested to undergo a tumor biopsy before treatment and after 6 weeks of treatment.
• Must have had appropriate treatment for their specific cancer and there is an absence of available therapy with a reasonable likelihood of conferring clinical benefit. Exclusion Criteria
• If the patient received prior therapy with an anti-PD-1 or anti-PD-L1 mAb or with an agent targeting stimulatory or co-inhibitory T-cell receptor and was discontinued from that treatment due to a Grade 3 or higher immune related adverse event.
• Received radiotherapy within 2 weeks of treatment.
• Received radiotherapy exceeding 30 Gray (Gy) to the lung within 6 months of the first dose of study medication.
• Received an allogeneic tissue/solid organ transplant.
• Received a live or live-attenuated vaccine within 30 days prior to the first dose of study medication.
• Received a VISTA targeting agent.
• The patient must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline.
• The patient has an active autoimmune disease that required systemic treatment in the past.
• Presence of an uncontrolled endocrine disorder.
• Presence of clinically significant cardiovascular disease.
• History of (non-infectious) pneumonitis or interstitial pulmonary disease that required steroids or has current pneumonitis or interstitial pulmonary disease.
• Presence of uncontrolled, clinically significant pulmonary disease.
• A previous a severe hypersensitivity reaction (≥ Grade 3) to pembrolizumab and/or any of its excipients.
• A diagnosis of immunodeficiency or is receiving chronic systemic corticosteroids at a dose that exceeds 10 mg daily of prednisone equivalent or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.
• An uncontrolled intercurrent illness that would limit compliance with the study.
• A positive status for human immunodeficiency virus (HIV).
• A known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C viral (defined as HCV RNA detected) infection.
• Oxygen-dependence.
• A medical condition which, in the opinion of the Investigator, places the patient at an unacceptably high risk for toxicity.
• A positive COVID test within one week of study treatment if not fully vaccinated.
• Another active malignancy that is progressing or has required active treatment within the past 3 years.
• Known active central nervous system metastases and/or carcinomatous meningitis.
Drug: HMBD-002, Drug: Pembrolizumab
Cancer, Metastatic Cancer, Triple Negative Breast Cancer, Advanced Solid Tumor, Nonsmall Cell Lung Cancer, Malignant Neoplasm, Breast - Female, Breast - Male, Lung/Thoracic, Melanoma, skin, Other Skin, Tumor, Solid
UT Southwestern
Cobimetinib in Refractory Langerhans Cell Histiocytosis (LCH), and Other Histiocytic Disorders (NACHO-COBI)
This is a research study of a drug called cobimetinib in children and adults diagnosed with Langerhans cell histiocytosis (LCH), and other histiocytic disorders that has returned or does not respond to treatment. Cobimetinib blocks activation of a protein called Mitogen-activated protein kinase (MEK) that is part of incorrect growth signals in histiocytosis cells. Four different groups of patients will be enrolled.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Erin Butler
104034
All
Not specified
Phase 2
NCT04079179
STU-2021-0830
INCLUSION CRITERIA:
Age at study entry
• For Group 1: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
• For Group 2: Participant may be at least 6 months of age at the time of enrollment
• For Group 3: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
• For Group 4: Participant must be 21 years of age or older at the time of enrollment
• Participant must be able to take an enteral dose and formulation of medication. Study medication is only available as an oral suspension or tablet which may be taken by mouth or other enteral route such as nasogastric or gastric tube.
• Biopsy proven LCH -AND
• Failure of at least front-line therapy for LCH with evaluable disease. -OR
• Diagnosis of LCH-associated neurodegenerative disease with radiologic or clinical progression within the past 3 months. -OR
• Biopsy proven JXG, ECD, RDD, histiocytic sarcoma, or other histiocytic lesion (newly diagnosed or relapsed/refractory disease) with evaluable active disease. Performance Level: -Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age. Adequate Hematologic Function Defined as:
• ANC ≥ 0.75 x 10^9/L (unsupported/without growth factor stimulant)
• Platelet count ≥ 75 x 10^9/L (unsupported/without transfusion within the past 7 days).
• Patients with marrow disease must have platelet count of >/= 75 x 10^9/L (transfusion support allowed) and must not be refractory to platelet transfusions.
• Hemoglobin ≥ 8 g/dL (unsupported/without transfusion within the past 7 days)
• Patients with marrow disease must have hemoglobin ≥ 8 g/dL (transfusion support allowed). Adequate Renal Function Defined as:
• Calculated creatinine clearance (or radioisotope GFR) ≥ 70 mL/min/1.73m^2 or serum creatinine based on age/gender as follows: Maximum Serum Creatinine (mg/dL) Age 2 to < 6 years: Male 0.8 mg/d, Female 0.8; 6 to < 10 years: Male 1 mg/dL,Female 1; 10 to < 13 years: Male 1.2 mg/dL; Female 1.2; 13 to < 16 years: Male 1.5 mg/dL ; Female 1.4; ≥ 16 years: Male 1.7 mg/dL; Female 1.4; Adequate Liver Function Defined as:
• Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
• AST and ALT ≤ 3x ULN (≤ 5 x ULN for participants with liver involvement)
• Serum albumin ≥ 2 g/dL. For patients with liver disease caused by histiocytic disorder: • Patients may be enrolled with abnormal bilirubin, AST, ALT and albumin with documentation of histiocytic liver disease. Adequate Cardiac Function Defined as:
• Fractional shortening (FS) of ≥ 30% or ejection fraction of ≥ 50% by echocardiogram at baseline, as determined by echocardiography or multigated acquisition scan (MUGA) within 28 days prior to enrollment. Depending on institutional standard, either FS or LVEF is adequate for enrollment if only one value is measured; if both values are measured, then both values must meet criteria above Pregnancy/Birth Control
• Female patients of childbearing potential require a negative urine or serum pregnancy test for eligibility and again at database registration, if more than 2 weeks has elapsed.
• Female patients of childbearing potential must agree to follow the contraceptive requirements using two forms of effective contraceptive methods for the duration of the study treatment. Male patients with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) must agree to use two forms of effective methods of contraception (one of which must be a barrier method) during the treatment period and for at least 3 months after the last dose of the study drug to avoid pregnancy and/or potential adverse effects on a developing embryo. Agreement to true abstinence (not periodic abstinence or withdrawal method) is an acceptable method of birth control. EXCLUSION CRITERIA:
• Prior and Concomitant Use of Drugs with CYP3A4 inducing/inhibiting activity: Patient taking strong inducers or inhibitors of CYP3A4 within 14 days prior to study enrollment, including but not limited to the following: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's wort.
• Prior Therapy Restrictions Completion of previous chemotherapy, immunotherapy, radiotherapy, or targeted therapy for LCH (or other histiocytic disorder) at least 28 days (except where specified below) prior to study enrollment, with resolution of all associated toxicity to ≤ Grade 1 prior to study enrollment (exception for alopecia and ototoxicity which do not need to be resolved ≤ Grade 1). Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the laboratory eligibility criteria are met, the patient is considered to have recovered adequately.
• Radiation therapy within the 28 days prior to enrollment.
• Any prior treatment with Cobimetinib.
• Treatment with a long-acting hematopoietic growth factor within 14 days prior to initiation of study drug or a short-acting hematopoietic growth factor within 7 days prior to enrollment.
• Treatment with hormonal therapy (except hormone replacement therapy or oral contraceptives), immunotherapy, biologic therapy, investigational therapy, or herbal cancer therapy within 28 days or < 5 half-lives, whichever is longer, prior to study enrollment.
• Treatment with high-dose chemotherapy and stem-cell rescue (autologous stem cell transplant) or allogeneic stem cell transplant within 90 days prior to enrollment. Anti-GVHD agents post-transplant: Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial.
• For patients with brain tumors (intracranial masses), use of anticoagulants within 7 days prior to enrollment.
• Corticosteroid therapy <0.5 mg/kg/day averaged during the month prior to study enrollment is permissible but must be discontinued fourteen (14) days prior to enrollment. Patients with documented brain lesions receiving corticosteroids for management of cerebral edema must be on a stable dose for fourteen (14) days prior to enrollment.
• Patient has received treatment with investigational therapy within 4 weeks prior to initiation of study drug.
• Patients taking anticoagulants or have a pre-existing bleeding disorder unrelated to histiocytic disease.
• Exclusions for other illness
• Other active malignancy or history of secondary malignancy.
• Refractory nausea and vomiting, malabsorption, external biliary shunt
• Infection: Patients who have a known active infection (excluding documented fungal infection of the nail beds) within 28 days prior to enrollment that has not completely resolved.
• Major surgical procedure or significant traumatic injury within 28 days prior to enrollment, or anticipation of need for major surgical procedure during the course of the study. Placement of a vascular access device or minor surgery is permitted within fourteen (14) days prior to study enrollment (provided that the wound has healed).
• History of significant bowel resection that would preclude adequate absorption or other significant malabsorptive disease.
• History of pneumonitis.
• Ophthalmologic considerations: Patients with known significant ophthalmologic conditions or known risk factors for retinal vein occlusion are not eligible. Specifically, patients with a history of retinal vein occlusion (RVO), retinal detachment, retinal pathology on ophthalmologic exam, retinopathy of prematurity, central serous chorioretinopathy (CSSCR), neovascular retinopathy, intraocular pressure > 21 mmHg, and predisposing factors to RVO (e.g., uncontrolled hypertension, diabetes, or hyperlipidemia, coagulopathy) will be excluded. Patients with longstanding and stable ophthalmologic findings secondary to existing conditions are eligible with appropriate written documentation and approval from Study Chair.
• History of solid organ transplantation: Patients who have received a prior solid organ transplantation are not eligible.
• Any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that in the opinion of the investigator contraindicates use of an investigational drug or places the patient at unacceptable risk from treatment complications.
• History of clinically significant cardiac dysfunction, including the following:
• Clinically significant cardiac arrhythmias including brady-arrhythmias and/or patients who require anti-arrhythmic therapy (with the exception of beta blockers or digoxin). Patients with controlled atrial fibrillation are not excluded.
• Unstable arrhythmia
• Unstable angina, or new-onset angina within 3 months prior to initiation of study treatment
• Symptomatic congestive heart failure, defined as New York Heart Association Class II or higher
• Myocardial infarction within 3 months prior to initiation of study treatment
• Known chronic human immunodeficiency virus (HIV).
• History of Grade ≥ 2 CNS hemorrhage or history of any CNS hemorrhage within 28 days of enrollment.
• Female patients who are pregnant or lactating. Pregnant or lactating women will not be entered on this study because there is no available information regarding human fetal or teratogenic toxicities.
• For Group 1: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
• For Group 2: Participant may be at least 6 months of age at the time of enrollment
• For Group 3: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
• For Group 4: Participant must be 21 years of age or older at the time of enrollment
• Participant must be able to take an enteral dose and formulation of medication. Study medication is only available as an oral suspension or tablet which may be taken by mouth or other enteral route such as nasogastric or gastric tube.
• Biopsy proven LCH -AND
• Failure of at least front-line therapy for LCH with evaluable disease. -OR
• Diagnosis of LCH-associated neurodegenerative disease with radiologic or clinical progression within the past 3 months. -OR
• Biopsy proven JXG, ECD, RDD, histiocytic sarcoma, or other histiocytic lesion (newly diagnosed or relapsed/refractory disease) with evaluable active disease. Performance Level: -Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age. Adequate Hematologic Function Defined as:
• ANC ≥ 0.75 x 10^9/L (unsupported/without growth factor stimulant)
• Platelet count ≥ 75 x 10^9/L (unsupported/without transfusion within the past 7 days).
• Patients with marrow disease must have platelet count of >/= 75 x 10^9/L (transfusion support allowed) and must not be refractory to platelet transfusions.
• Hemoglobin ≥ 8 g/dL (unsupported/without transfusion within the past 7 days)
• Patients with marrow disease must have hemoglobin ≥ 8 g/dL (transfusion support allowed). Adequate Renal Function Defined as:
• Calculated creatinine clearance (or radioisotope GFR) ≥ 70 mL/min/1.73m^2 or serum creatinine based on age/gender as follows: Maximum Serum Creatinine (mg/dL) Age 2 to < 6 years: Male 0.8 mg/d, Female 0.8; 6 to < 10 years: Male 1 mg/dL,Female 1; 10 to < 13 years: Male 1.2 mg/dL; Female 1.2; 13 to < 16 years: Male 1.5 mg/dL ; Female 1.4; ≥ 16 years: Male 1.7 mg/dL; Female 1.4; Adequate Liver Function Defined as:
• Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
• AST and ALT ≤ 3x ULN (≤ 5 x ULN for participants with liver involvement)
• Serum albumin ≥ 2 g/dL. For patients with liver disease caused by histiocytic disorder: • Patients may be enrolled with abnormal bilirubin, AST, ALT and albumin with documentation of histiocytic liver disease. Adequate Cardiac Function Defined as:
• Fractional shortening (FS) of ≥ 30% or ejection fraction of ≥ 50% by echocardiogram at baseline, as determined by echocardiography or multigated acquisition scan (MUGA) within 28 days prior to enrollment. Depending on institutional standard, either FS or LVEF is adequate for enrollment if only one value is measured; if both values are measured, then both values must meet criteria above Pregnancy/Birth Control
• Female patients of childbearing potential require a negative urine or serum pregnancy test for eligibility and again at database registration, if more than 2 weeks has elapsed.
• Female patients of childbearing potential must agree to follow the contraceptive requirements using two forms of effective contraceptive methods for the duration of the study treatment. Male patients with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) must agree to use two forms of effective methods of contraception (one of which must be a barrier method) during the treatment period and for at least 3 months after the last dose of the study drug to avoid pregnancy and/or potential adverse effects on a developing embryo. Agreement to true abstinence (not periodic abstinence or withdrawal method) is an acceptable method of birth control. EXCLUSION CRITERIA:
• Prior and Concomitant Use of Drugs with CYP3A4 inducing/inhibiting activity: Patient taking strong inducers or inhibitors of CYP3A4 within 14 days prior to study enrollment, including but not limited to the following: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's wort.
• Prior Therapy Restrictions Completion of previous chemotherapy, immunotherapy, radiotherapy, or targeted therapy for LCH (or other histiocytic disorder) at least 28 days (except where specified below) prior to study enrollment, with resolution of all associated toxicity to ≤ Grade 1 prior to study enrollment (exception for alopecia and ototoxicity which do not need to be resolved ≤ Grade 1). Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the laboratory eligibility criteria are met, the patient is considered to have recovered adequately.
• Radiation therapy within the 28 days prior to enrollment.
• Any prior treatment with Cobimetinib.
• Treatment with a long-acting hematopoietic growth factor within 14 days prior to initiation of study drug or a short-acting hematopoietic growth factor within 7 days prior to enrollment.
• Treatment with hormonal therapy (except hormone replacement therapy or oral contraceptives), immunotherapy, biologic therapy, investigational therapy, or herbal cancer therapy within 28 days or < 5 half-lives, whichever is longer, prior to study enrollment.
• Treatment with high-dose chemotherapy and stem-cell rescue (autologous stem cell transplant) or allogeneic stem cell transplant within 90 days prior to enrollment. Anti-GVHD agents post-transplant: Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial.
• For patients with brain tumors (intracranial masses), use of anticoagulants within 7 days prior to enrollment.
• Corticosteroid therapy <0.5 mg/kg/day averaged during the month prior to study enrollment is permissible but must be discontinued fourteen (14) days prior to enrollment. Patients with documented brain lesions receiving corticosteroids for management of cerebral edema must be on a stable dose for fourteen (14) days prior to enrollment.
• Patient has received treatment with investigational therapy within 4 weeks prior to initiation of study drug.
• Patients taking anticoagulants or have a pre-existing bleeding disorder unrelated to histiocytic disease.
• Exclusions for other illness
• Other active malignancy or history of secondary malignancy.
• Refractory nausea and vomiting, malabsorption, external biliary shunt
• Infection: Patients who have a known active infection (excluding documented fungal infection of the nail beds) within 28 days prior to enrollment that has not completely resolved.
• Major surgical procedure or significant traumatic injury within 28 days prior to enrollment, or anticipation of need for major surgical procedure during the course of the study. Placement of a vascular access device or minor surgery is permitted within fourteen (14) days prior to study enrollment (provided that the wound has healed).
• History of significant bowel resection that would preclude adequate absorption or other significant malabsorptive disease.
• History of pneumonitis.
• Ophthalmologic considerations: Patients with known significant ophthalmologic conditions or known risk factors for retinal vein occlusion are not eligible. Specifically, patients with a history of retinal vein occlusion (RVO), retinal detachment, retinal pathology on ophthalmologic exam, retinopathy of prematurity, central serous chorioretinopathy (CSSCR), neovascular retinopathy, intraocular pressure > 21 mmHg, and predisposing factors to RVO (e.g., uncontrolled hypertension, diabetes, or hyperlipidemia, coagulopathy) will be excluded. Patients with longstanding and stable ophthalmologic findings secondary to existing conditions are eligible with appropriate written documentation and approval from Study Chair.
• History of solid organ transplantation: Patients who have received a prior solid organ transplantation are not eligible.
• Any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that in the opinion of the investigator contraindicates use of an investigational drug or places the patient at unacceptable risk from treatment complications.
• History of clinically significant cardiac dysfunction, including the following:
• Clinically significant cardiac arrhythmias including brady-arrhythmias and/or patients who require anti-arrhythmic therapy (with the exception of beta blockers or digoxin). Patients with controlled atrial fibrillation are not excluded.
• Unstable arrhythmia
• Unstable angina, or new-onset angina within 3 months prior to initiation of study treatment
• Symptomatic congestive heart failure, defined as New York Heart Association Class II or higher
• Myocardial infarction within 3 months prior to initiation of study treatment
• Known chronic human immunodeficiency virus (HIV).
• History of Grade ≥ 2 CNS hemorrhage or history of any CNS hemorrhage within 28 days of enrollment.
• Female patients who are pregnant or lactating. Pregnant or lactating women will not be entered on this study because there is no available information regarding human fetal or teratogenic toxicities.
Drug: Cobimetinib
Histiocytic Sarcoma, Juvenile Xanthogranuloma, Brain and Nervous System, Bones and Joints, Liver, Lung/Thoracic, Other Hematopoietic, Langerhan's Cell Histiocytosis, Erdheim-Chester Disease, Rosai Dorfman Disease, Neuro-Degenerative Disease, Histiocytic Disorders, Malignant
Cobimetinib, Langerhans Cell Histiocytosis (LCH)
Children’s Health
Abatacept in Immune Checkpoint Inhibitor Myocarditis (ATRIUM)
The primary aim is to test whether abatacept, as compared to placebo, is associated with a reduction in major adverse cardiac events (MACE) among participants hospitalized with myocarditis secondary to an immune checkpoint inhibitor (ICI). The primary outcome, MACE, is a composite of first occurrence of cardiovascular death, non-fatal sudden cardiac arrest, cardiogenic shock, significant ventricular arrythmias, significant bradyarrythmias, or incident heart failure.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Vlad Zaha
163027
All
18 Years and over
Phase 3
NCT05335928
STU-2022-0624
Inclusion Criteria:
• Must have provided informed consent in a manner approved by the Investigator's Institutional Review Board (IRB) prior to any study-related procedure being performed. If a participant is unable to provide informed consent due to his/her medical condition, the participant's legally authorized representative may consent on behalf of the study participant, as permitted by local law and institutional Standard Operating Procedures;
• Aged greater than or equal to 18 years at the time of informed consent;
• Recent use of an FDA-approved immune checkpoint inhibitor (ICI, defined as administered an immune checkpoint inhibitor ≤ 6 months of myocarditis diagnosis), alone or in combination with other cancer therapies (i.e. chemotherapy, radiation therapy or targeted therapy). The FDA-approved ICI could be given as part of a clinical trial but not in combination with a new investigational agent which may cause myocarditis;
• A diagnosis of myocarditis.
• Hospitalized at the time of randomization;
• On 1000 mg of solumedrol per day for myocarditis or with an intent to initiate 1000 mg of solumedrol per day for myocarditis within 24 hours of first administration of study drug;
• Serum evidence of ongoing myocardial injury: Serum evidence of ongoing myocardial injury will be defined as an institutional troponin (either conventional or high-sensitivity troponin I or T, using the standard institutional assay) with a value that is ≥5 times the upper limit of the reference standard normal for that institution. The troponin assay may be adjusted based on sex depending on institutional standards. This value of troponin of ≥5 times above the institutional upper limits of normal value must be noted within 10 days prior to potential randomization. The 10-day period can be in the outpatient or inpatient setting. For example, a participant with a troponin value that on one occasion was ≥5 times the upper limits of institutional normal in the 10-day window prior to potential randomization (whether in the inpatient or outpatient setting), but later decreases below that threshold, typically due to starting corticosteroids, would still be considered eligible;
• The following laboratory parameters, not older than 48 hours at the time of randomization, and measured as part of usual care:
• Total white blood cell (WBC) count >2,500/μl
• Absolute neutrophil count (ANC) >1,500/μL
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) <20 times the upper limit of the institutional normal ranges;
• Women of childbearing potential (i.e., not postmenopausal, or surgically sterilized) must have a negative highly sensitive urine or serum pregnancy test prior to randomization. Participating women of childbearing potential must be willing to consistently use effective methods of contraception from screening until at least 90 days after administration of the last dose of study drug. Participating men must also be willing to consistently use effective methods of contraception from screening until at least 90 days after administration of the last dose of study drug; and
• Must be willing and able to abide by all study requirements and restrictions.
Exclusion Criteria:
• Must not have experienced any of the following (as defined in the section on the primary endpoint) in the 30-day period prior to randomization:
• A sudden cardiac arrest
• Cardiogenic shock as defined. A significant bradyarrhythmia (Mobitz type II second degree atrioventricular block or third degree (complete) atrio-ventricular (AV) block, for which an intervention with a temporary or permanent pacemaker is completed or recommended).
• A significant tachyarrhythmia (ventricular fibrillation of any duration or sustained ventricular tachycardia (>30 seconds, >120 beats per minute); or a ventricular tachyarrhythmia requiring intervention.
• Recent (≤2 month) exposure to abatacept or belatacept.
• Concurrent or recent (≤2 month) use of the following non-corticosteroid immunosuppressive therapies prior to randomization: mycophenolate, JAK STAT inhibitors (including but not limited to upadacitinib, tofacitinib, baricitinib, and filgotinib), tacrolimus, anti-thymocyte globulin, alemtuzumab, infliximab, and plasma exchange. The use of intravenous immunoglobulin is permitted prior to randomization and during study treatment.
• Currently enrolled in another interventional study utilizing systemic agents for the management of ICI-related toxicities.
• Female who is pregnant, breastfeeding, or is considering becoming pregnant during the study or for approximately 90 days after the last dose of study drug.
• Male who is considering fathering a child or donating sperm during the study or for approximately 30 days after the last dose of study drug.
• Any active, chronic, or recurrent viral infection that, based on the investigator's clinical assessment, makes the participant an unsuitable candidate for the study. These may include hepatitis B virus (HBV) or hepatitis C virus (HCV), recurrent or disseminated (even a single episode) herpes zoster, and disseminated (even a single episode) herpes simplex. Active HBV and HCV are defined as: HBV: hepatitis B surface antigen (HBs Ag) positive (+) or detected sensitivity on the HBV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) qualitative test for Hepatitis B core antibody (HBc Ab) positive (+) participants; HCV: HCV ribonucleic acid (RNA) detectable in any participant with anti-HCV antibody (HCV Ab). Patients with active Covid-19 infection will be excluded. This is defined as the period of ongoing symptoms in the setting of a positive Covid-19 test, or until 10 days after symptom onset and after resolution of fever for at least 24 hours, without the use of fever-reducing medications.
• Known active tuberculosis (TB), history of incompletely treated TB, suspected or known extrapulmonary TB, suspected or known systemic bacterial or fungal infections;
• Receipt of any live vaccine within four weeks prior to the first dose of study drug, or expected need of live vaccination during study participation including at least 90 days after the last dose of IV study drug.
• Any medical condition that could interfere with, or for which the treatment might interfere with, the conduct of the study or interpretation of the study results, or that would, in the opinion of the Investigator, increase the risk of the participant by participating in the study.
• Any factors that, in the Investigator's opinion, are likely to interfere with study procedures, such as history of noncompliance with scheduled appointments.
Drug: Abatacept plus, Drug: Placebo
Cancer, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Thyroid, Urinary Bladder, Small Intestine, Soft Tissue, Unknown Sites, Myocarditis Acute
Immune checkpoint Inhibitor, Myocarditis, Abatacept, Immune therapy, Immune related adverse events
UT Southwestern
A Study of ZN-c3 in Participants With Solid Tumors
This is a Phase 1/2 open-label, multicenter study, evaluating the safety, tolerability, efficacy, pharmacokinetics (PK) and pharmacodynamics of ZN-c3 alone and in combination with other drugs.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Miller
14954
All
18 Years and over
Phase 1
NCT04158336
STU-2021-0811
Key
• Provision of written informed consent.
• Age ≥ 18 years or the minimum legal adult age (whichever is greater) at the time of informed consent.
• Adequate hematologic and organ function as defined by the following criteria:
• Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L; excluding measurements obtained within 7 days after daily administration of filgrastim/sargramostim or within 3 weeks after administration of pegfilgrastim.
• Platelet count ≥ 100 × 10^9/L; excluding measurements obtained within 3 days after transfusion of platelets.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN). If liver function abnormalities are due to underlying liver metastases, AST and ALT ≤ 5 x ULN.
• Total serum bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN in the case of Gilbert's disease.
• Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 60 mL/min.
• Female subjects of childbearing potential must have a negative serum beta human chorionic gonadotropin test.
• Male subjects and female subjects of childbearing potential must agree to use an effective method of contraception per institutional standard prior to the first dose and for 90 days after the last dose of ZN-c3. Individuals must meet the additional criteria in order to be eligible to participate in Phase 1:
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Measurable or evaluable disease per RECIST version 1.1. Individuals must meet these additional criteria in order to be eligible to participate in Phase 2 Single Agent part of the study:
• ECOG performance status ≤ 1.
• Measurable disease per RECIST version 1.1. Individuals must meet these additional criteria in order to be eligible to participate in Phase 2 combination with a PARP inhibitor:
• ECOG performance status ≤ 1.
• Measurable disease per RECIST version 1.1. Individuals must meet these additional criteria in order to be eligible to participate in Phase 2 combination with a PD-1 inhibitor:
• ECOG performance status ≤ 1.
• Measurable disease per RECIST version 1.1. Key
• Any of the following treatment interventions within the specified time frame prior to Cycle 1 Day 1:
• Major surgery within 28 days.
• Radiation therapy within 21 days.
• Any prior systemic therapy regardless of the stop date, but the subject must have recovered to eligibility levels from prior toxicity.
• Autologous or allogeneic stem cell transplant within 3 months.
• Current use of an investigational agent that is not expected to be cleared by the first dosing of study drug or that has demonstrated to have prolonged side effects. Subjects should have recovered from the side effects to a Grade 0 or 1 (except alopecia).
• A serious illness or medical condition(s) including, but not limited to, the following:
• Brain metastases that require immediate treatment or are clinically or radiologically unstable.
• Leptomeningeal disease that requires or is anticipated to require immediate treatment.
• Myocardial impairment of any cause resulting in heart failure by New York Heart Association Criteria Class III or IV.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the Investigator would make the subject inappropriate for entry into this study.
• Significant gastrointestinal abnormalities
• Active or uncontrolled infection.
• Unresolved toxicity of Grade > 1 attributed to any prior therapies (excluding Grade 2 neuropathy, alopecia or skin pigmentation).
• Prior therapy with ZN-c3 or known hypersensitivity to any drugs similar to ZN-c3 in class.
• Subjects with active (uncontrolled, metastatic) second malignancies or requiring therapy.
Inclusion Criteria:
In order to be eligible to participate in any phase of this study, an individual must meet
all of the following criteria:
• Provision of written informed consent.
• Age ≥ 18 years or the minimum legal adult age (whichever is greater) at the time of informed consent.
• Adequate hematologic and organ function as defined by the following criteria:
• Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L; excluding measurements obtained within 7 days after daily administration of filgrastim/sargramostim or within 3 weeks after administration of pegfilgrastim.
• Platelet count ≥ 100 × 10^9/L; excluding measurements obtained within 3 days after transfusion of platelets.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN). If liver function abnormalities are due to underlying liver metastases, AST and ALT ≤ 5 x ULN.
• Total serum bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN in the case of Gilbert's disease.
• Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 60 mL/min.
• Female subjects of childbearing potential must have a negative serum beta human chorionic gonadotropin test.
• Male subjects and female subjects of childbearing potential must agree to use an effective method of contraception per institutional standard prior to the first dose and for 90 days after the last dose of ZN-c3. Individuals must meet the additional criteria in order to be eligible to participate in Phase 1:
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Measurable or evaluable disease per RECIST version 1.1. Individuals must meet these additional criteria in order to be eligible to participate in Phase 2 Single Agent part of the study:
• ECOG performance status ≤ 1.
• Measurable disease per RECIST version 1.1. Individuals must meet these additional criteria in order to be eligible to participate in Phase 2 combination with a PARP inhibitor:
• ECOG performance status ≤ 1.
• Measurable disease per RECIST version 1.1. Individuals must meet these additional criteria in order to be eligible to participate in Phase 2 combination with a PD-1 inhibitor:
• ECOG performance status ≤ 1.
• Measurable disease per RECIST version 1.1. Key
Exclusion Criteria:
• Any of the following treatment interventions within the specified time frame prior to Cycle 1 Day 1:
• Major surgery within 28 days.
• Radiation therapy within 21 days.
• Any prior systemic therapy regardless of the stop date, but the subject must have recovered to eligibility levels from prior toxicity.
• Autologous or allogeneic stem cell transplant within 3 months.
• Current use of an investigational agent that is not expected to be cleared by the first dosing of study drug or that has demonstrated to have prolonged side effects. Subjects should have recovered from the side effects to a Grade 0 or 1 (except alopecia).
• A serious illness or medical condition(s) including, but not limited to, the following:
• Brain metastases that require immediate treatment or are clinically or radiologically unstable.
• Leptomeningeal disease that requires or is anticipated to require immediate treatment.
• Myocardial impairment of any cause resulting in heart failure by New York Heart Association Criteria Class III or IV.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the Investigator would make the subject inappropriate for entry into this study.
• Significant gastrointestinal abnormalities
• Active or uncontrolled infection.
• Unresolved toxicity of Grade > 1 attributed to any prior therapies (excluding Grade 2 neuropathy, alopecia or skin pigmentation).
• Prior therapy with ZN-c3 or known hypersensitivity to any drugs similar to ZN-c3 in class.
• Subjects with active (uncontrolled, metastatic) second malignancies or requiring therapy.
Drug: ZN-c3
Small Cell Lung Cancer, Fallopian Tube Cancer, Non Small Cell Lung Cancer, Malignant Melanoma, Metastatic Breast Cancer, Triple Negative Breast Cancer, Epithelial Ovarian Cancer, Urothelial Carcinoma, Solid Tumor, Corpus Uteri, Peritoneal Cancer
Solid tumor
UT Southwestern; Parkland Health & Hospital System