Here are the studies that match your search criteria. If you are interested in participating, please reach out to the contact listed for the study. If no contact is listed, contact us and we'll help you find the right person.
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.
• 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
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.
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
The iCat2, GAIN (Genomic Assessment Informs Novel Therapy) Consortium Study
This research study is evaluating the use of specialized testing of solid tumors including
sequencing. The process of performing these specialized tests is called tumor profiling. The
tumor profiling may result in identifying changes in genes of the tumor that indicate that a
particular therapy may have activity. This is called an individualized cancer therapy (iCat)
recommendation. The results of the tumor profiling and, if applicable, the iCat
recommendation will be returned.
• Age -- Age ≤ 30 years at time of initial qualifying solid tumor diagnosis
• Diagnosis -- Histologic diagnosis of solid malignancy (excluding brain tumors and
lymphoma) that meets at least one of the following criteria:
• Refractory, defined as tumor progression after initiation of standard first line
therapy without having achieved a prior partial or complete remission OR Biopsy
proven residual disease at the completion of planned standard initial front-line
therapy.
• Recurrent, defined as tumor progression after achieving a prior partial or
complete remission
• Newly diagnosed high risk disease, defined as having an expected event free
survival of < 50% at 2 years.
• Lacks definitive diagnosis or classical genomic findings after histologic review
and standard molecular testing (rare tumor group).
• Examples include (eligibility not limited to these examples):
• Histology typically associated with a fusion in which fusion is not detected.
• Ewing-like sarcoma
• Undifferentiated sarcoma
• Inflammatory myofibroblastic tumor without ALK fusion
• Infantile fibrosarcoma without NTRK fusion
• Specimen Samples
• Sufficient tumor specimen available to meet the minimum requirements for
profiling from diagnosis or progression / recurrence
--- OR
• Surgery / biopsy planned as part of clinical care that is anticipated to yield
sufficient material to meet the minimum requirements for profiling; OR
• Patient has already had molecular profiling and patient has not yet started
matched targeted therapy based on the report .
Exclusion Criteria:
• No Therapy Planned
-- Patients who have declined further anticancer therapy will be excluded.
• Performance Status
-- Patients with Lansky (age < 16 years) or Karnofsky (age ≥16 years) score < 50 will
be excluded.
• Life Expectancy -- Patients with anticipated life expectancy < 3 months will be
excluded.
Genetic: Genetic testing and GAIN report
Sarcoma, Pediatric Solid Tumor, Brain and Nervous System, Other, Eye and Orbit, Anklylosing Spondylitis, Anus, Bones and Joints, Breast - Female, Breast - Male, Carcinoid Tumor, 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, Heart, Kaposis sarcoma, Small Intestine, Soft Tissue, Ill - Defined Sites
A Study of LY3484356 in Participants With Advanced or Metastatic Breast Cancer or Endometrial Cancer (EMBER)
The reason for this study is to see if the study drug LY3484356 alone or in combination with
other anticancer therapies is safe and effective in participants with advanced or metastatic
breast cancer or endometrial cancer.
All study parts:
• Participants must be willing to provide adequate archival tissue sample
• Participants must be willing to use highly effective birth control
• Participants must have adequate organ function
• Participants must be able to swallow capsules
Dose escalation- Participants must have one of the following:
• Parts A and B: ER+ HER2- breast cancer with evidence of locally advanced unresectable
or metastatic disease who have had the following:
• Part A: may have had up to 1 prior regimen of any kind for in the advanced/metastatic
setting and no prior cyclin-dependent kinase 4/6 (CDK4/6) inhibitor therapy.
• Part B: may have had up to 2 prior regimens, no more than 1 of which may be endocrine
therapy in the advanced/metastatic setting, and must have received a prior CDK4/6
inhibitor
• Cohort E4: No prior everolimus.
• Cohort E5: No prior alpelisib and must have a phosphatidylinositol 3-kinase catalytic
α (PIK3Cα) mutation as determined by local testing.
• Part C: ER+, human epidermal growth factor receptor 2 positive (HER2+) breast cancer
with evidence of locally advanced unresectable or metastatic disease who have had at
least 2 HER2-directed therapies in any setting.
• Part D: ER+, EEC that has progressed after platinum containing chemotherapy and no
prior fulvestrant or aromatase inhibitor therapy.
• Part E: ER+ and HER2+ breast cancer with evidence of locally advanced, unresectable,
or metastatic disease.
• Part E: Participants must have received induction taxane chemotherapy combined with
trastuzumab + pertuzumab as first-line treatment for advanced/metastatic disease and
must not have progressed on this regimen.
• Part E: Participants must not have received more than 1 HER2-directed regimen or any
endocrine therapy for advanced disease or any prior CDK4/6 inhibitor therapy.
Participants with ER+/HER2- breast cancer enrolled in this study must have had evidence of
clinical benefit while on endocrine therapy for at least 24 months in the adjuvant setting
or at least 6 months in the advanced/metastatic setting or have untreated de novo
metastatic breast cancer
Exclusion Criteria:
• Participants must not have certain infections such as hepatitis or tuberculosis or HIV
that are not well controlled
• Participants must not have another serious medical condition
• Participants must not have cancer of the central nervous system that is unstable
• Participants must not be pregnant or breastfeeding
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.
1. 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;
2. Aged greater than or equal to 18 years at the time of informed consent;
3. 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;
4. A diagnosis of myocarditis.
5. Hospitalized at the time of randomization;
6. 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;
7. 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;
8. 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;
9. 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
10. Must be willing and able to abide by all study requirements and restrictions.
Exclusion Criteria:
1. 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.
2. Recent (≤2 month) exposure to abatacept or belatacept.
3. 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.
4. Currently enrolled in another interventional study utilizing systemic agents for the
management of ICI-related toxicities.
5. 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.
6. 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.
7. 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.
8. Known active tuberculosis (TB), history of incompletely treated TB, suspected or known
extrapulmonary TB, suspected or known systemic bacterial or fungal infections;
9. 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.
10. 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.
11. 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
Phase 1/2a Evaluation of Adding AL3818 to Standard Platinum-Based Chemotherapy in Subjects With Recurrent or Metastatic Endometrial, Ovarian, Fallopian, Primary Peritoneal or Cervical Carcinoma (AL3818-US-002) (AL3818)
This trial is a Phase 1b/2a trial designed to evaluate the safety and efficacy of adding oral
AL3818 to standard platinum-based chemotherapy concurrently and continued as a maintenance
therapy for up to 12 months.
• Female ≥ 18 years
• Previously histologically proven diagnosis of
a. Endometrial Cancer: recurrent or persistent endometrial carcinoma refractory to
conventional therapy or established treatments with the following histologic
epithelial cell types i. Endometrioid adenocarcinoma, serous adenocarcinoma,
undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma,
adenocarcinoma not otherwise specified, mucinous adenocarcinoma, squamous cell
carcinoma, and transitional cell carcinoma b. Ovarian Cancer: recurrent or persistent
ovarian or primary peritoneal cancer refractory to established treatments with the
following histologic epithelial cell types i. Endometrioid adenocarcinoma, serous
adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed
epithelial carcinoma, adenocarcinoma not otherwise specified.
c. Cervical cancer: squamous cell carcinoma of the cervix refractory to conventional
therapy or established treatments with the following histologic epithelial cell types:
i. Squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma Measurable
disease defined as at least one lesion that can be accurately measured in at least one
dimension (longest dimension to be recorded). Each lesion must be ≥ 20mm when measured
by conventional techniques, including palpation, plain x-ray, CT, and MRI or ≥ 10mm
when measured by spiral CT.
• Life expectancy ≥ 3 months
• Able to take orally administered study medication
• Must sign approved informed consent and authorization permitting release of personal
health information.
• Patient must have adequate:
1. Bone marrow function: absolute neutrophil count (ANC) ≥ 1,500/mm^3, equivalent to
Common Toxicity Criteria (CTC) grade 1, platelets ≥ 100,000/mm^3
2. Renal function: creatinine ≤ 1.5 x institutional upper limit normal (ULN), CTC
grade 1. Note: If creatinine is > 1.5 x ULN, creatinine clearance must be > 50
mL/min.
3. Hepatic function: bilirubin ≤ 1.5 x ULN (CTC grade 1) or ≤ 3.0 x ULN for subjects
with Gilbert Syndrome; AST and ALT ≤ 3.0 ×ULN.
4. Coagulation profile: PT such that international normalized ratio (INR) is ≤ 1.55
(or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of
therapeutic warfarin or low molecular weight heparin) and a PTT < 1.2 times
control.
5. ECOG performance ≤ 2
• Patient of child-bearing potential must agree to use contraceptive measures starting 1
week before the administration of the first dose of AL3818 until 4 weeks after
discontinuing study drug and have a negative serum pregnancy test prior to study entry
and cannot be lactating.
• Ability and willingness to comply with the study protocol for the duration of the
study and with follow-up procedures.
Exclusion Criteria:
• Patients with serious, non-healing wound, ulcer or bone fracture.
• Patients with active bleeding or pathologic conditions that carry high risk of
bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major
vessels.
• Patient with history or evidence upon physical examination of CNS disease, including
primary brain tumor, seizures not controlled with standard medical therapy, any brain
metastases or history of cerebrovascular accident (CVA, stroke) transient ischemic
attack (TIA) or subarachnoid hemorrhage within 6 months of the first date of treatment
on this study.
a. Patients with metastatic CNS tumors may participate in this trial, if the patient
is > 4 weeks from therapy completion (including radiation and/or surgery), is
clinically stable at the time of study entry and is not receiving corticosteroid
therapy.
• Patients with proteinuria: patients discovered to have a urine protein of 1+ on
dipstick or ≥ 30 mg/dl at baseline should undergo a 24-hour urine collection, which
must be an adequate collection and must demonstrate < 1000 mg protein/24 hours to
allow participation in the study.
• Patients with clinically significant cardiovascular disease including uncontrolled
hypertension, myocardial infarction or unstable angina within 6 months prior to
registration. New York Heart Association (NYHA) Grade II or greater congestive heart
failure, Serious cardiac arrhythmia requiring medication, Grade II or greater
peripheral vascular disease.
• Patients who are pregnant or nursing.
• Women of childbearing potential who are unable to use contraceptive measures during
study therapy and for at least 3 months after completion of AL3818 therapy.
• Patients with uncontrolled hypokalemia, hypomagnesaemia, and/or hypocalcaemia.
• Hemoptysis within 3 months prior to first scheduled dose of AL3818.
• Patients with acute or chronic liver disease, active hepatitis A or B with known
cirrhosis or liver dysfunction.
• Cytotoxic chemotherapy, immunotherapy, or radiotherapy within 4 weeks (6 weeks in
cases of mitomycin C, nitrosourea, lomustine) prior to first scheduled dose of AL3818
or a major surgical procedure within 28 days or minor surgical procedure performed
within 7 days prior to first scheduled dose of AL3818.
• Concomitant treatment with strong inhibitors or inducers of CYP3A4, CYP2C9 and CYP2C19
who cannot be switched to other alternative medications .
• Known history of human immunodeficiency virus infection (HIV).
• Subjects with active bacterial infections (other than uncomplicated urinary tract
infection) and/or receiving systemic antibiotics.
• Patients with other invasive malignancies, with the exception of non-melanoma skin
cancer, who had (or have) any evidence of other cancer present within the last 5 years
or whose previous cancer treatment contraindicates this protocol therapy.
• History of non-malignant GI bleeding, gastric stress ulcerations, or peptic ulcer
disease within the past 3-months that in the opinion of the investigator may place the
patient at risk of side effects on an anti-angiogenesis product.
• History of significant vascular disease (e.g. aortic aneurysm, aortic dissection).
• Intra-abdominal abscess within the last 3 months.
• Pre-existing uncontrolled hypertension as documented by 2 baseline BP readings taken
at least one hour apart, defined as systolic bloodpressure (BP) >160 mm Hg or
diastolic BP > 90 mm Hg pressure.
• QTcF>470 msec on screening ECG.
• A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family
history of Long QT Syndrome).
• The use of concomitant medications that prolong the QT/QTc interval. Baseline
echocardiogram (within 2 months) with left ventricular ejection fraction (LVEF) < 50%.
• History of difficulty swallowing, malabsorption, active partial or complete bowel
obstruction, or other chronic gastrointestinal disease or condition that may hamper
compliance and/or absorption of AL3818.
• History of pancreatitis and/or renal disease or pancreatitis that includes
histologically confirmed glomerulonephritis, biopsy proven tubulointerstitial
nephritis, crystal nephropathy, or other renal insufficiencies.
• Treatment with an investigational agent within the longest time frame of either 5
half- lives or 30 days of initiating study drug.
• Known recreational substance abuse.
• Known hypersensitivity to AL3818 or components of the formulation.
Digital Tomosynthesis Mammography and Digital Mammography in Screening Patients for Breast Cancer
This randomized phase III trial studies digital tomosynthesis mammography and digital
mammography in screening patients for breast cancer. Screening for breast cancer with
tomosynthesis mammography may be superior to digital mammography for breast cancer screening
and may help reduce the need for additional imaging or treatment.
• Women of childbearing potential must not be known to be pregnant or lactating
• Patients must be scheduled for, or have intent to schedule, a screening mammogram
• Patients must be able to tolerate digital breast tomosynthesis and full-field digital
mammographic imaging required by protocol.
• Patients must be willing and able to provide a written informed consent
• Patients must not have symptoms or signs of benign or malignant breast disease (eg,
nipple discharge, breast lump) warranting a diagnostic rather than a screening
mammogram, and/or other imaging studies (eg, sonogram); patients with breast pain are
eligible as long as other criteria are met
• Patients must not have had a screening mammogram within the last 11 months prior to
date of randomization
• Patients must not have previous personal history of breast cancer including ductal
carcinoma in situ
• Patients must not have breast enhancements (e.g., implants or injections)
• ANNUAL SCREENING REGIMEN ELIGIBILITY CHECK
• To be eligible for inclusion in the annual screening regimen one of the following
three conditions must be met in addition to the eligibility criteria above:
• Patients are pre-menopausal; OR
• Post-menopausal aged 45-69 with any of the following three risks factors:
• Dense breasts (BIRADS density categories c-heterogeneously dense or
d-extremely dense), or
• Family history of breast cancer (first degree relative with breast cancer),
or, positive genetic testing for any deleterious genes that indicate an
increased risk for breast cancer, or
• Currently on hormone therapy; OR
• Post-menopausal ages 70-74 with either of the following two risk factors:
• Dense breasts (BIRADS density categories c-heterogeneously dense or
d-extremely dense), or
• Currently on hormone therapy
• Postmenopausal women are defined as those with their last menstrual period more than
12 months prior to study entry; for the purpose of defining menopausal status for
women who have had surgical cessation of their periods, women who no longer have
menses due to hysterectomy and oophorectomy will be considered postmenopausal; women
who no longer have menses due to hysterectomy without oophorectomy will be considered
premenopausal until age 52 and postmenopausal thereafter
• All other postmenopausal women are eligible for inclusion in the biennial screening
regimen
• For those women who cannot be assigned to annual or biennial screening at the time of
study entry and randomization because they are postmenopausal, have no family history
or known deleterious breast cancer mutation, are not on hormone therapy AND have not
had a prior mammogram, breast density will be determined by the radiologist?s
recording of it at the time of interpretation of the first study screening
examination, either DM or TM; for those who are randomized to TM, radiologists will
assign BI-RADS density through review of the DM or synthetic DM portion of the TM
examination; such women cannot be part of the planned stratification by screening
frequency and are expected to represent far less than 1% of the Tomosynthesis
Mammographic Imaging Screening Trial (TMIST) population
• Breast density will be determined by prior mammography reports, when available; all
other risk factors used to determine patient eligibility for annual or biennial
screening will be determined by subject self-report
Procedure: Digital Mammography, Procedure: Digital Tomosynthesis Mammography, Other: Laboratory Biomarker Analysis
Breast Screening, Breast - Female
Digital Mammography, Breast Tomography, Screening Mammography, TMIST
A Study of Abemaciclib (LY2835219) With Abiraterone in Men With Prostate Cancer That Has Spread to Other Parts of the Body and is Expected to Respond to Hormonal Treatment (Metastatic Hormone-Sensitive Prostate Cancer) (CYCLONE 3)
The purpose of this study is to learn whether adding abemaciclib to abiraterone plus
prednisone prolongs the time before prostate cancer gets worse. Participation may last
approximately 60 months.
• Adenocarcinoma of the prostate (as the predominant histology)
• High-risk metastatic hormone-sensitive prostate cancer. High risk is defined as:
• Greater than or equal to (≥)4 bone metastases by bone scan and/or
• ≥1 visceral metastases by computed tomography or magnetic resonance imaging
• Must have initiated androgen deprivation therapy (ADT) with luteinizing
hormone-releasing hormone (LHRH) agonist/antagonist or bilateral orchiectomy prior to
randomization. Up to 3 months of ADT prior to randomization is permitted with or
without first-generation anti-androgen.
• Adequate organ function
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Exclusion Criteria:
• Prior treatment with abemaciclib or any other cyclin dependent kinase 4 and 6 (CDK4 &
6) inhibitor
• Development of metastatic prostate cancer in the context of castrate levels of
testosterone
• Received any prior systemic therapy for metastatic prostate cancer (including
investigational agents), except for ADT and first-generation anti-androgen
• Clinically significant cardiovascular disease as evidenced by myocardial infarction,
arterial thrombotic events, or severe/unstable angina in the past 6 months, or New
York Heart Association Class II to IV heart failure
• History of syncope of cardiovascular etiology, ventricular arrhythmia of pathological
origin, or sudden cardiac arrest. Chronic and hemodynamically stable atrial arrhythmia
well-controlled on medical therapy is permitted
• Uncontrolled hypertension
• Clinically active or chronic liver disease, moderate/severe hepatic impairment
• Known untreated central nervous system (CNS) metastasis. Participants with a history
of treated brain metastases are eligible if stable for at least 8 weeks prior to
randomization and off corticosteroid for at least 2 weeks prior to randomization
Drug: Abemaciclib, Drug: Abiraterone, Drug: Prednisone or Prednisolone, Drug: Placebo for Abemaciclib
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.
• Have advanced breast cancer or another solid tumor with the presence of a PIK3CA
H1047R mutation (or other Sponsor and 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 one bone lesion in breast cancer patients
only)
• For patients with an 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+/HER2- advanced breast cancer
• Patients may have had up to 2 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
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 PI3K/AKT/mTOR inhibitor(s), except in certain circumstances
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
A Trial of Robotic Versus Open Hysterectomy Surgery in Cervix Cancer (ROCC)
This is a randomized controlled trial to compare survival for patients who undergi robotic
assisted laparoscopy versus open radical hysterectomy and lymph node assessment for the
treatment of early stage cervical cancer.
1. Patient must have histologically confirmed adenocarcinoma (usual/classic/NOS),
squamous cell carcinoma, adenosquamous carcinoma (Including glassy cell)
2. Patient must be FIGO Stage IA2, IBI, IB2 (2018 staging) without evidence of definitive
parametrial, vaginal, nodal or distant metastases on exam or imaging.
3. Patient must have uterine size <12 cm AND felt to be appropriate for vaginal delivery
of the specimen per investigator.
4. Patient must be suitable surgical candidate with preoperative assessments such as labs
and EKG performed per institutional standard.
5. Patient must be age 18 years or older.
6. Patient must have ECOG performance status 0-1.
7. Patient must have a negative urine pregnancy test within 30 days of surgery in
pre-menopausal women.
8. Patient must have signed an approved informed consent and authorization permitting the
release of personal health information.
Exclusion Criteria:
1. Patients with any tumor histology other than those listed above, specifically
excluding the following histologies: neuroendocrine, other adenocarcinoma (gastric
type, endometrioid, clear cell, serous, signet ring, minimal deviation)
2. Patients with FIGO stage 1A1, IB3, II-IV (2018 staging).
3. Patient with inability to receive an MRI.
4. Patients with a tumor size ≥4cm or with definite evidence of vaginal/parametrial
involvement on MRI (if MRI findings are not definitive, then clinical examination must
also reveal parametrial or vaginal extension).
5. Patients with evidence of metastatic disease (imaging or histologically positive lymph
nodes).
6. Patients with a history of prior pelvic or abdominal radiotherapy.
7. Patients with a prior malignancy < 5 years from enrollment with the exception of
non-melanoma skin cancer.
8. Patients who are unable to withstand prolonged lithotomy or steep trendelenberg.
9. Patient compliance and geographic proximity that do not allow adequate follow-up.
10. Patients with poorly controlled HIV with CD4 counts <500.
Stereotactic Radiosurgery (SRS) 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.
Inclusion Criteria
1. Biopsy-proven non-hematopoietic malignancy, except for small cell lung cancer, germ
cell cancer, or unknown primary tumor.
2. 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)
3. All brain metastases must be outside the brain stem (midbrain, pons and medulla).
4. Patient must have 10 or less brain metastases.
5. The maximum diameter of any lesion must be less than or equal to 3.0 cm.
6. 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
7. Age ≥ 18 years.
8. ECOG Performance Score of 2 or better/Karnofsky Performance Status score of 50-60 or
better.
9. 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)
10. Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria
1. Patients had craniotomy and surgery to the brain within 7 days from the date of SRS.
2. 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.
3. Patients with a contraindication to both MRI (with or without contrast) and CT scan
(with contrast)
4. Patients with life expectancy < 3 months.
5. 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.
6. 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
Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT)
The researchers are doing the study to see if semaglutide may reduce the risk of having
cardiovascular events in patients with overweight or obesity and with prior cardiovascular
disease. The participant will either get semaglutide (active medicine) or placebo ("dummy"
medicine). Which treatment the participants get is decided by chance. The participant's
chance of getting semaglutide or placebo is the same. The participant will get the study
medicine in a pen. The participants will need to use the pen to inject the study medicine in
a skinfold once a week. The study will last for about 2.5 to 5 years. Participants will have
up to 25 clinic visits with the study doctor.
•Male or female, age greater than or equal to 45 years at the time of
signing informed consent •Body mass index (BMI) greater than or equal to 27 kg/m^2 •Have
established cardiovascular (CV) disease as evidenced by at least one of the following:
prior myocardial infarction; prior stroke (ischemic or haemorrhagic stroke); or symptomatic
peripheral arterial disease (PAD), as evidenced by intermittent claudication with
ankle-brachial index (ABI) less than 0.85 (at rest), or peripheral arterial
revascularization procedure, or amputation due to atherosclerotic disease Exclusion
Criteria: •Any of the following: myocardial infarction, stroke, hospitalisation for
unstable angina pectoris or transient ischaemic attack within the past 60 days prior to the
day of screening •HbA1c greater than or equal to 48 mmol/mol (6.5 %) as measured by the
central laboratory at screening •History of type 1 or type 2 diabetes (history of
gestational diabetes is allowed)
Drug: Semaglutide, Drug: Placebo (semaglutide)
Obesity, Overweight
UT Southwestern; Parkland Health & Hospital System
GammaPod Registry and Quality of Life Nomogram (GCC 1876)
This study is a prospective, single arm study (registry) summarizing patient-level
adverse-event and tumor outcomes as well as a number of feasibility and dosimetric
characteristics of delivering a single-fraction boost with the GammaPod.
• The patient must sign consent for study participation.
• The patient must be female and have a diagnosis of an invasive or non-invasive breast
cancer that was treated surgically by a partial mastectomy.
• The patient must be deemed an appropriate candidate for breast conserving therapy
(i.e. not pregnant, never had radiation to the treated breast, breast size would allow
adequate cosmesis after volume loss from partial mastectomy).
• Patients with involved lymph nodes are candidates for the study.
• Surgical margins are negative for invasive (no tumor on ink) or non-invasive breast
cancer (2 mm negative margin).
• The greatest dimension of the tumor is less than 4cm before surgery.
• Multifocal disease is allowed if it was removed by a single lumpectomy resection and
the patient remained a candidate for breast conservation.
• Age 18 years and older.
• Women of childbearing potential (pre-menopausal defined as having a menstrual period
within the past 1 year) must have a negative serum pregnancy test or complete a
pregnancy waiver form per institutional policy.
• The surgical cavity is clearly visible on CT images. Of note, clips are not required
but recommended.
• The patient must weigh less than 150Kg (330lb), which is the limit of the imaging
couch.
• The patient must be less than 6'6" in height.
• The patient must feel comfortable in the prone position.
• Diagnosis of prior contralateral breast cancer is allowed.
• Diagnosis of synchronous bilateral cancers is allowed. In this case if bilateral
boosts are required, a patient would not have both treatments on the same day.
• Oncoplastic reduction surgery is allowed if the lumpectomy cavity can be clearly
visualized.
Exclusion Criteria:
• Patients with proven multi-centric carcinoma (tumors in different quadrants of the
breast or tumor separated by at least 4 cm).
• Prior radiation therapy to that breast or that hemi thorax.
• Unable to fit into the immobilization breast cup with an adequate seal.
• Male gender.
• Patient cannot comfortably be set up in the prone position (i.e. physical disability)
• Unable to fit into the breast immobilization device due to breast size or other
anatomical reason.
• Mastectomy is the surgery performed.
• Patient has received prior radiotherapy to the involved breast.
• Tumor bed is less than 3 mm from the skin surface.
• Greater than 50% of the target volume is above the upper border of the table.
• Patients with skin involvement, regardless of tumor size.
• Patients with connective tissue disorders specifically systemic lupus erythematosis,
scleroderma, or dermatomyositis.
• Patients with psychiatric or addictive disorders that would preclude obtaining
informed consent.
• Patients who are pregnant or lactating due to potential exposure of the fetus to RT
and unknown effects of RT to lactating females.
• Patients with breast implants/tissue expanders or flap reconstruction.
Radiation: Quality Of Life Sizing Nomogram
Breast Cancer Female, Breast - Female
Breast Nomogram, Breast Cancer Quality of Life, GammaPod Registry
UT Southwestern; 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). 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).
Inclusion:
1. 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.
2. Age ≥2 and <21 years at the time of study entry.
3. 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.
4. Adequate bone marrow function.
• Absolute neutrophil count ≥1000/mm3;
• Platelet count ≥100,000/mm3 (transfusion independent, no platelet transfusion in
past 7 days prior study entry);
• Hemoglobin ≥8.5 g/dL (transfusion allowed).
5. Adequate renal function: Serum creatinine level based on age/gender must within
protocol specified limits.
6. 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.
7. 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 INRC for neuroblastoma. 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).
8. 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.
9. Serum/urine pregnancy test (for all girls ≥8 years of age) negative at screening and
at the baseline visit.
Exclusion:
1. 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.
2. 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.
3. Use of strong cytochrome P450 (CYP) 3A inhibitors or inducers. 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.)
4. Systemic anti cancer therapy within 2 weeks prior to study entry and 6 weeks for
nitrosoureas.
5. Prior irradiation to >50% of the bone marrow (see Appendix 9).
6. Participation in other studies involving investigational drug(s) within 2 weeks or 5
half lives, whichever is longer, prior to study entry.
7. Major surgery within 4 weeks prior to study entry. Surgical biopsies or central line
placement are not considered major surgeries.
8. For IRN and TMZ with/without palbociclib combinations: known or suspected
hypersensitivity to palbociclib, IRN and/or TMZ. For combination of palbociclib with
TOPO and CTX: known or suspected hypersensitivity to palbociclib, TOPO and/or CTX.
9. 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.
10. 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.
11. Hereditary bone marrow failure disorder.
12. QTc >470 msec.
13. 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%.
14. Recent or ongoing clinically significant gastrointestinal disorder that may interfere
with absorption of orally administered drugs (eg, gastrectomy).
15. 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.
16. 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.
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
A Study of TAS-120 in Patients With Metastatic Breast Cancer
The purpose of the trial is to evaluate a patient's response to a Fibroblast Growth Factor
Receptor (FGFR) inhibitor, futibatinib (TAS-120), used either alone or in combination with
the hormonal therapy, fulvestrant. This study will be conducted in patients with metastatic
breast cancer who have specific Fibroblast Growth Factor Receptor gene abnormalities and who
have previously received conventional therapies to treat their breast cancer, or who are not
able to tolerate certain cancer therapies. This study will also evaluate the safety of taking
futibatinib, or futibatinib and fulvestrant, by learning about the potential side effects.
1. Provide written informed consent
2. Age ≥ 18 years of age
3. Histologically or cytologically confirmed recurrent locally advanced or metastatic
breast cancer not amenable to treatment with curative intent, and the following cohort
specific criteria:
A. Cohort 1
• HR+ HER2- breast cancer harboring an FGFR2 gene amplification.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST)
Version 1.1
• Has received 1-3 prior endocrine-containing therapies and up to 2 prior
chemotherapy regimens for advanced/metastatic disease
• Has received prior treatment with a CDK4/6 inhibitor or is ineligible for such
treatment
B. Cohort 2
• TNBC harboring an FGFR2 gene amplification
• Measurable disease per RECIST 1.1
• Has received at least 1 prior chemotherapy or chemotherapy/immunotherapy
(PD-L1/PD-1 inhibitors) regimen for advanced/metastatic disease C. Cohort 3
• TNBC or HR+ HER2- breast cancer harboring an FGFR2 gene amplification
• Non measurable, evaluable disease per RECIST 1.1. Patients with bone-only disease
must have lytic or mixed lytic-blastic lesions
• Other criteria for either HR+ HER2- breast cancer or TNBC should be met as
described for Cohort 1 and 2, respectively
D. Cohort 4
• HR+ HER2- breast cancer harboring an FGFR1 high-level gene amplification
• Measurable disease per RECIST 1.1
• Has received 1-2 prior endocrine-containing therapies and no more than 1 prior
chemotherapy regimen for advanced/metastatic disease. Prior treatment with
fulvestrant is not permitted.
• Has received prior treatment with a CDK4/6 inhibitor or is ineligible for such
treatment
• Pre/peri-menopausal patients must be on goserelin
4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
5. Archival or (preferably) fresh tumor tissue must be available
6. Adequate organ function
Exclusion Criteria:
1. History and/or current evidence of any of the following disorders:
1. Non-tumor related alteration of the calcium-phosphorus homeostasis that is
considered clinically significant
2. Ectopic mineralization/calcification, including but not limited to soft tissue,
kidneys, intestine, or myocardia and lung, considered clinically significant
3. Retinal or corneal disorder confirmed by retinal/corneal examination and
considered clinically significant
2. Prior treatment with an FGFR inhibitor
3. A serious illness or medical condition(s)
4. Brain metastases that are untreated or clinically or radiologically unstable
5. Pregnant or lactating female
Drug: Futibatinib, Drug: Futibatinib plus Fulvestrant
Metastatic Breast Cancer, FGFR2 Amplification, Breast - Female, Breast - Male, FGFR 1 High Amplification
Futibatinib, Metastatic Breast Cancer, FGFR, TAS-120
UT Southwestern; Parkland Health & Hospital System
Comparison of Standard of Care Treatment With a Triplet Combination of Targeted Immunotherapeutic Agents
This phase II trial studies the possible benefits of treatment with different combinations of
the drugs durvalumab, olaparib and cediranib vs. the usual treatment in patients with
ovarian, primary peritoneal, or fallopian tube cancer that has come back after a period of
improvement with platinum therapy (recurrent platinum resistant). Usual treatment is the type
of treatment most patients with this condition receive if they are not part of a clinical
study. Combination therapies studied in this trial include MEDI4736 (durvalumab) plus
olaparib and cediranib, durvalumab and cediranib, or olaparib and cediranib. Monoclonal
antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may
interfere with the ability of tumors cells to grow and spread. Olaparib is an inhibitor of
PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged.
Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to
die. PARP inhibitors are a type of targeted therapy. Cediranib may stop the growth of tumor
cells by blocking VEGF (an enzyme). needed for cell growth. Giving different combinations of
durvalumab, olaparib and cediranib may work better in increasing the duration of time that
the cancer does not progress compared to the usual treatment.
• Women with recurrent/persistent platinum-resistant ovarian, primary peritoneal, or
fallopian tube cancers; platinum-resistant disease is defined as progression within <
6 months from completion of platinum based therapy. The date should be calculated from
the last administered dose of platinum therapy
• Patients must have histologically or cytologically confirmed ovarian cancer,
peritoneal cancer or fallopian tube cancer and must have a histological diagnosis of
high grade serous, grade 3 endometrioid or clear cell carcinoma based on local
histopathological findings. Patients with low grade serous, grade 1 or 2 endometrioid,
mixed epithelial, undifferentiated carcinoma, or mucinous carcinoma histologies are
also eligible, provided that the patient has a known deleterious BRCA1 or BRCA2
mutation identified through testing at a clinical laboratory. Histologic confirmation
of the original primary tumor is required via the pathology report (upload of report
required). Confirmation of BRCA1 and BRCA2 germline and/or somatic mutation status and
hormone receptor (HR) status is required for all entered patients (if available) via
testing report (upload of report[s] required)
• Evaluable disease •defined as RECIST 1.1 measurable disease OR non-measurable disease
(defined as solid and/or cystic abnormalities on radiographic imaging that do not meet
RECIST 1.1 definitions for target lesions OR ascites and/or pleural effusion that has
been pathologically demonstrated to be disease-related in the setting of a CA125 >= 2
x upper limit of normal [ULN])
• Prior therapy:
• At least two prior treatment regimens (including primary therapy) but up to 5
lines of systemic anticancer therapy. Hormonal therapy (such as tamoxifen,
aromatase inhibitors) will not count as a previous treatment regimen.
• Prior use of bevacizumab in the upfront or recurrent setting is required.
• Prior use of PARP inhibitor is allowed.
• Prior use of immune checkpoint blockade (e.g., a PD-L1/PD-1inhibitor or a CTLA-4
inhibitor) is allowed
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Absolute neutrophil count (ANC) >= 1,500/mcL
• Hemoglobin > 10 g/dL
• Platelets >= 100,000/mcL
• Creatinine clearance (CrCL) or estimated glomerular filtration rate (eGFR) of > 50
mL/min estimated using either the Cockcroft-Gault equation, the Modification of Diet
in Renal Disease Study, or as reported in the comprehensive metabolic panel/basic
metabolic panel (eGFR)
• Urine protein: creatinine ratio (UPC) of =< 1
• Total serum bilirubin level =< 1.5 x ULN (patients with known Gilbert's disease who
have bilirubin level =< 3 x ULN may be enrolled)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN
• Age >= 18 years
• Body weight > 30 kg
• Adequately controlled blood pressure (systolic blood pressure [SBP] =< 140; diastolic
blood pressure [DBP] =< 90 mmHg) on a maximum of three antihypertensive medications.
Patients must have a BP of =< 140/90 mmHg taken in the clinic setting by a medical
professional within 2 weeks prior to study registration. It is strongly recommended
that patients who are on three antihypertensive medications be followed by a
cardiologist or a primary care physician for management of BP while on protocol.
Patients must be willing and able to check and record daily blood pressure readings.
BP cuffs will be provided to patients randomized to the cediranib-containing arms
• Adequately controlled thyroid dysfunction with no symptoms of thyroid dysfunction and
normal thyroid stimulating hormone (TSH). If TSH is not within normal range despite no
symptoms of thyroid dysfunction, normal free T4 level is required
• Able to swallow and retain oral medications and no gastrointestinal (GI) illnesses
that would preclude absorption of olaparib and cediranib as judged by treating
physician
• Toxicities of prior therapy (excepting alopecia and vitiligo), should be resolved to
less than or equal to grade 1 as per Common Terminology Criteria for Adverse Events
(CTCAE) v5.0
• Women of childbearing potential (WOCBP) must agree to use two forms of birth control
(hormonal or barrier method of birth control; abstinence). Note: Definition of women
of no longer having childbearing potential: Postmenopausal or evidence of
non-childbearing status for women of childbearing potential as confirmed by a negative
urine or serum pregnancy test within 7 days prior to start of study treatment.
Postmenopausal is defined as: Age >= 60 years, or age < 60 with any one or more of the
conditions below:
• Amenorrhoeic for >= 1 year in the absence of chemotherapy and/or hormonal
treatments,
• Luteinizing hormone and/or follicle stimulating hormone and/or estradiol levels
in the post-menopausal range,
• Radiation-induced oophorectomy with last menses > 1 year ago,
• Chemotherapy-induced menopause with > 1 year interval since last menses,
• Surgical sterilization (bilateral oophorectomy or hysterectomy)
• The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry and authorization permitting release of personal
health information
Exclusion Criteria:
• Primary platinum-refractory disease defined as progression during first-line
platinum-based chemotherapy
• Rising CA-125 only without RECIST 1.1 evaluable disease
• Prior therapy:
• Patients who have had chemotherapy, investigational drugs or radiotherapy within
3 weeks prior to study registration or those who have not recovered from adverse
events due to agents administered more than 3 weeks earlier.
• Patients may not have had hormonal therapy within 2 weeks of study registration.
Patients receiving raloxifene for bone health as per Food and Drug Administration
(FDA) indication may remain on raloxifene absent other drug interactions.
• Prior use of concurrent olaparib and cediranib combination.
• Patients who have experienced immune-mediated adverse events requiring dose
modification or discontinuation.
• For patients who have received prior PARP inhibitor:
• Patients who have required dose modification or dose reduction of olaparib
will not be eligible, as they will not be able to start this study at full
dose.
• Patients who have required dose reduction of non-olaparib PARP inhibitors
for hematologic adverse events will not be eligible (Note: niraparib that is
initiated at 200mg daily per weight and platelet guidelines is not
considered a dose reduction).
• Patients who required dose-reduction of non-olaparib PARP inhibitors for
non-hematologic adverse events may be eligible after discussion with the
Study Chair if the treating investigator feels that they could appropriately
receive olaparib at full dose.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
within 3 months prior to study registration
• Current signs and/or symptoms of bowel obstruction or signs and/or symptoms of bowel
obstruction within 3 months of study registration except temporary (< 24 hr) improved
with medical management, within last 3 months
• Any prior grade >= 3 immune-related adverse event (irAE) while receiving any previous
immunotherapy agent, or any unresolved irAE > grade 1
• Dependency on IV hydration or total parenteral nutrition (TPN)
• Pregnant women. Because there is an unknown but potential risk of adverse events in
nursing infants secondary to treatment of the mother with these drugs, breastfeeding
should be discontinued. These potential risks may also apply to other agents used in
this study
• Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial
• Patients with untreated brain metastases, spinal cord compression, or evidence of
symptomatic brain metastases or leptomeningeal disease as noted on computed tomography
(CT) or magnetic resonance imaging (MRI) scans should not be included on this study,
since neurologic dysfunction may confound the evaluation of neurologic and other
adverse events. Patients with treated brain metastases and resolution of any
associated symptoms must demonstrate stable post-therapeutic imaging for at least 6
months following therapy prior to starting study registration
• Patients who have the following clinical conditions are considered to be at increased
risk for cardiac toxicities. Patients with any cardiac history of the following
conditions:
• History of myocardial infarction or myocarditis within six months of study
registration
• Unstable angina
• Resting electrocardiogram (ECG) with clinically significant abnormal findings.
• New York Heart Association functional classification of III or IV
• If cardiac function assessment is clinically indicated or performed: left ventricular
ejection fraction (LVEF) less than normal per institutional guidelines, or < 55%, if
threshold for normal not otherwise specified by institutional guidelines. Patients
with the following risk factors should have a baseline cardiac function assessment:
• Prior treatment with anthracyclines
• Prior treatment with trastuzumab or T-DM1
• Prior central thoracic radiation therapy (RT), including RT to the heart
• History of myocardial infarction within 6 to 12 months (Patients with history of
myocardial infarction within 6 months are excluded from the study)
• Prior history of impaired cardiac function
• History of stroke or transient ischemic attack within six months of study registration
• Clinically significant peripheral vascular disease or vascular disease (aortic
aneurysm or aortic dissection)
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the
first dose of study treatment. Patients must have recovered from any effects of any
major surgery and surgical wound should have healed prior to starting treatment. Note:
Local surgery of isolated lesions for palliative intent is acceptable
• Evidence of coagulopathy or bleeding diathesis. Therapeutic anticoagulation for prior
thromboembolic events, including warfarin, is permitted. Patients receiving warfarin
are recommended to have careful monitoring of international normalized ratio (INR)
• Evidence suggestive of myelodysplastic syndrome (MDS) or acute myelogenous leukemia
(AML) on peripheral blood smear or bone marrow biopsy, if clinically indicated. No
prior allogeneic bone marrow transplant or double umbilical cord blood transplantation
(dUBCT)
• Human immunodeficiency virus (HIV) positive patients due to potential drug and drug
interactions
• Patients may not use any complementary or alternative medicines including natural
herbal products or folk remedies as they may interfere with the effectiveness of the
study treatments
• Receipt of live attenuated vaccine within 30 days prior to the first dose of study
treatment. Note: Patients, if enrolled, should not receive live vaccine whilst
receiving study treatment and up to 30 days after the last dose of study treatment
• Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia (other than atrial fibrillation with controlled ventricular rate), or
psychiatric illness/social situations that would limit compliance with study
requirements, substantially increase risk of incurring adverse events or compromise
the ability of the patient to given written informed consent
• Patients receiving any medications or substances that are strong inhibitors or
inducers of CYP3A4. Dihydropyridine calcium-channel blockers are permitted for
management of hypertension
• Current or prior use of immunosuppressive medication within 14 days of study
registration. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication)
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to durvalumab, olaparib, or cediranib
• Patients with active autoimmune disease that has required systemic treatment in the
past 2 years (i.e., with use of disease modifying agents, corticosteroids, or
immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,
etc.) is not considered a form of systemic treatment
• Active infection including tuberculosis (clinical evaluation that includes clinical
history, physical examination and radiographic findings, and tuberculosis [TB] testing
in line with local practice), hepatitis B (known positive hepatitis B virus [HBV]
surface antigen (HBsAg) result), or hepatitis C. Patients with a past or resolved HBV
infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence
of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible
only if polymerase chain reaction is negative for hepatitis C virus (HCV) ribonucleic
acid (RNA)
• Patients who have a history of (non-infectious) pneumonitis that required steroids, or
current pneumonitis
To observe the effects of radiofrequency ablation on adenomyosis through the pathological
analysis of treated tissue that has been removed during planned hysterectomy.
• planning to undergo an abdominal, laparoscopic, or robotic-assisted hysterectomy due
to benign conditions
• uterus < 16 weeks gestational size if undergoing a laparoscopic or robotic procedure
(no size limit for patients planning to undergo a transabdominal hysterectomy)
• at least one area of focal or diffuse adenomyosis or adenomyomas that is/are
contralateral to any fibroids as determined by MRI
• able to provide informed consent
• suitable candidates for surgery (have passed a standard pre-operative health
assessment)
• English speaking
Exclusion Criteria:
• require emergent hysterectomy or vaginal hysterectomy
• have a uterus > 16 weeks gestational size if undergoing a laparoscopic or robotic
procedure (no size limit for patients planning to undergo a transabdominal
hysterectomy)
• have fibroids in the proximity of the target adenomyosis (same side, similar location)
• are not appropriate surgical candidates as determined during pre-operative health
assessment
• are unable or unwilling to undergo a hysterectomy
• are pregnant or lactating
• are under the age of 18 years
• have active pelvic inflammatory disease
• have a history of gynecologic malignancy within the past 3 years
• are unable to give informed consent
• have an implantable uterine or fallopian tube device for contraception
• are not English speaking
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.
• 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 > 1410 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)
Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity (STEP-HFpEF)
This study will look at how the participants daily life is affected by their heart failure.
The study will also look at the change in participants body weight from the start to the end
of the study.
This is to compare the effect on heart failure symptoms and on body weight in people taking
semaglutide (a new medicine) to people taking "dummy" medicine.
Participants will either get semaglutide or "dummy" medicine - which treatment participants
get is decided by chance.
Participants will need to take 1 injection once a week. The study medicine is injected with a
thin needle in a skin fold in the stomach area, thigh or upper arm.
During the study participants will have talks with the study staff about healthy lifestyle
choices including healthy food and physical activity.
The study will last for approximately 59 weeks. Participants will have 11 clinic visits and 1
phone call with the study doctor. Women: Women cannot take part if they are pregnant,
breast-feeding or plan to become pregnant during the study period.
• Male or female, age above or equal to 18 years at the time of signing informed
consent.
• Body mass index (BMI) greater than or equal to 30.0 kg/m^2
• New York Heart Association (NYHA) Class II-IV
• Left ventricular ejection fraction (LVEF) greater than or equal to 45 percentage at
screening
Exclusion Criteria:
• A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before
screening irrespective of medical records
• Haemoglobin A1c (HbA1c) greater than or equal to 6.5 percentage (48 mmol/mol) based on
latest available value from medical records, no older than 3 months or if unavailable
a local measurement at screening
A Research Study to See How Well CagriSema Helps People With Excess Body Weight Lose Weight (REDEFINE 1)
This study has 2 parts: First part is the main study and second part is the extension study.
During the main study participants will receive 1 of 4 study medicines. If participants
continue in the extension study, they will not receive any study medicine during the
extension. The main study will look at how well CagriSema helps participants with excess body
weight lose weight compared to a "dummy" medicine and 2 other medicines, cagrilintide and
semaglutide. Participants will either get CagriSema, cagrilintide,semaglutide or "dummy"
medicine. Which treatment participants get is decided by chance. They will take one injection
once a week. The study medicine is injected briefly with a thin needle, typically in the
stomach, thighs or upper arms.
Extension study: After the main study, not all participants will continue in the extension
study. The study staff will tell the participant if they will continue or not into the
extension study. In the extension study we will look at what happens to the participant's
body weight and diseases related to excess body weight after the participant stops taking the
study medicine. The main study will last for about 1½ years and the extension study will last
for another 2 years.
• Male or female
• Age above or equal to 18 years at the time of signing informed consent
• Body mass index (BMI) greater than or equal to 30.0 kilograms per square meter
(kg/m^2) or b) BMI greater than or equal to 27.0 kg/m^2 with the presence of at least
one weight-related comorbidity including, but not limited to hypertension,
dyslipidaemia, obstructive sleep apnoea or cardiovascular disease
Exclusion Criteria:
•Glycaemia related: a) Glycated Haemoglobin (HbA1c) greater than or equal to 6.5 percent
(48 millimoles per mole [mmol/mol]) as measured by the central laboratory at screening b)
History of type 1 or type 2 diabetes mellitus
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.
• 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
A Neurosteroid Intervention for Menopausal and Perimenopausal Depression
HYPOTHESIS:
Pregnenolone administration will be associated with greater reduction in depressive symptom
severity than placebo in women with current mMDD.
STUDY AIMS:
Primary Aim: Determine if pregnenolone is associated with greater reduction in depressive
symptom severity than placebo in women with mMDD, as measured by MADRS.
Secondary Aims:
1. Determine if pregnenolone is associated with greater reduction in anxiety symptom
severity than placebo in women with mMDD.
2. Determine if pregnenolone is associated with greater improvement in cognition than
placebo in women with mMDD.
3. Determine if pregnenolone is associated with greater improvement in quality of life than
placebo in women with mMDD.
4. Determine if pregnenolone is associated with greater improvement in vasomotor symptoms
of menopause than placebo.
Mechanistic Aims:
1. Determine whether changes in neurosteroid levels with pregnenolone mediate clinical
response.
2. Determine if baseline neurosteroid levels predict pregnenolone response.
3. Determine whether depressive symptoms, anxiety, sleep or vasomotor symptoms improve
first. A crossed-lagged panel model will explore serial correlations between changes in
outcome measures.
The participants must meet the following criteria:
• Women aged 40-62 years who are perimenopausal or early postmenopausal (within 5 years
of the last menstrual period if not surgically postmenopausal), including:
• Women who have experienced changes in menstrual cycle frequency or duration, and/or
physical symptoms indicative of menopausal transition, as determined by clinician
• Women who are using hormonal IUDs (i.e. brands Mirena and Skyla), with FSH level > 20
mIU/m (as menstrual periods are irregular with IUDs that utilize hormones, making
irregular/absent periods difficult to assess as related to the menopausal transition).
• Women with significant menopause-related physical symptoms, indicated by any of the
following criteria:
• Greene Climacteric Scale total scores > 20
• Greene Climacteric Scale sub-score for vasomotor symptoms >3
• 5 or more bothersome hot flashes per week (self-reported)
• Women meeting DSM-5 criteria for current major depressive disorder (assessed by the
SCID)
• Baseline HRSD score of ≥ 18
• Subject agrees to abstain from disallowed medications for the duration of the trial
Exclusion Criteria:
The participants must not meet any of the following criteria:
• Vulnerable populations (e.g. pregnant/nursing, severe cognitive or intellectual
impairment, incarcerated)
• Pregnancy (determined by urine pregnancy test), intending pregnancy or breast feeding
• Psychiatric disorder other than MDD that is acute and the primary focus of symptom
burden or treatment.
• History of bipolar disorder or psychotic disorder
• Current substance use disorder
• Positive baseline urine drug screen of an illicit substance (in this study: opioids
and cocaine,) with the exception of a medication used with a prescription (use of a
detected substance that is used with a prescription, such as an opioid pain
medication, is not necessarily exclusionary and will be based upon judgment of the PI,
particularly in the cases of chronic opioid use). Participants who screen positive for
marijuana will be offered a rescreen for eligibility at a later date.
• Current eating disorder
• Treatment resistant depression (failure of 2 adequate antidepressant trials or
electroconvulsive therapy (ECT) during current episode; adequate antidepressant trials
are defined as within the US FDA approved dosage for the medication and used for at
least 6 weeks, with failure described by the patient as <50% improvement based on her
subjective experience).
• High risk for suicidal acts including active suicidal ideation with plan and intent or
> 2 suicide attempts in lifetime or any attempt in the past 6 months
• Use of selective estrogen-receptor modulators (SERMs), hormone replacement therapy,
hormonal contraceptives (hormonal IUDs allowed), episodic sleep medications (chronic,
regular, stable-dose benzodiazepines and hypnotics such as zolpidem, Sonata
(Zaleplon), and Lunesta (Eszopiclone) OR sleep-seating antihistamines such as Unisom
(Doxylamine succinate) or diphenhydramine allowed) within 2 weeks of the baseline
visit and randomization. Antidepressants will be allowed for those participants who
have been taking the antidepressant for 6 weeks with a stable dose for at least 4
weeks.
• Use of natural menopause and depression supplements, phytoestrogens, soy-based
medications, steroids within 2 weeks of baseline visit and randomization.
• Use of any disallowed medications (specified in the Excluded Concomitant Medication
section below).
• Women who have received a gonadal hormonal intervention within 1 month prior to study
entry (stable thyroid medications are allowed).
• Not using a medically approved method of birth control, if sexually active and not 12
or more months since last menstrual period IUDs, condoms, abstinence are acceptable
forms of contraception in this study; due to the possible interactions with the study
medication, oral contraceptive pills will be prohibited.
• Uncontrolled hypertension (>160/95mmHg)
• Active coronary artery disease, atrial fibrillation, stroke, deep vein thrombosis,
pulmonary embolism or blood clotting disorder
• Any severe, life threatening or unstable medical condition that, based on
clinician-judgment, would make participation in the study unsafe or inappropriate
• Personal or first degree family history of known hormone sensitive tumors
• History of allergic reaction or side effects with prior pregnenolone use
• Clinically significant laboratory or physical examination findings
• Concurrent enrollment in another clinical trial
Exclusion of Concomitant Medications:
• Selective estrogen-receptor modulators (SERMs)
• Hormone replacement therapy
• Hormonal contraceptives, excluding Mirena IUD or other IUD with localized progesterone
• Natural menopause or antidepressant supplements
• Episodic sleep medications (chronic, regular, stable-dose benzodiazepines and
hypnotics such as zolpidem, Sonata (Zaleplon), and Lunesta (Eszopiclone) OR
sleep-sedating antihistamines such as Unisom (Doxylamine succinate) or diphenhydramine
allowed)
• Sub-therapeutic dosages of antidepressants used for other indications will be
permissible with the exclusion of SSRIs, SNRIs, and Wellbutrin.
• Phytoestrogens
• Soy-based medications or supplements
Drug: Pregnenolone, Drug: Placebo
Major Depressive Disorder, Menopause, Perimenopause
Evaluation of [18F]FLT PET/CT as an Early Predictor of Outcome in Pediatric Solid Tumors
The experimental [18F]FLT-PET/CT will be completed before initiation of chemotherapy at
either diagnosis or initiation of salvage chemotherapy at relapse and prior to the third
cycle (or month) of chemotherapy. Laboratory analysis and correlative radiology, as directed
per clinical care based on the primary diagnosis, are required within 30 days of the baseline
[18F]FLT PET/CT. Follow-up will comprise 24 months of standard practice treatment and follow
up.
• Patients with histologically confirmed solid tumor malignancies with residual tumors
present that require standard of care chemotherapy for a minimum number of cycles. All
anatomical sites and all tumor histologies are eligible including central nervous
system tumors. Both newly diagnosed and/or newly relapsed patients are eligible.
• Patients ages 8 •25 years
• In the opinion of the investigator, patients must be thought to be able to lie still
for imaging without sedation for 20 •30 minutes.
• Patients must have a performance status of > 50% (Lansky or Karnofsky).
• Patients of childbearing potential must have a negative urine or serum pregnancy test
as per institution's standard of care within 7 days prior to [18F]FLT PET/CT imaging.
• Ability to understand and the willingness to sign a written informed consent/assent.
Exclusion Criteria:
• Patients with known allergic or hypersensitivity reactions to previously administered
radiopharmaceuticals of similar chemical or biologic composition to [18F]FLT
• Newly diagnosed subjects who had prior chemotherapy or radiotherapy before enrollment
in the study. Relapsed patients are eligible prior to starting their relapsed
chemotherapy regimen if they meet the other eligibility criteria.
• Subjects for whom chemotherapy is not a standard of care primary therapy option.
• Patients who are pregnant or breast-feeding.
• Patients with no residual tumor (i.e. complete resection at diagnosis or relapse).
Drug: [18F]FLT-PET/CT
Sarcoma, Solid Tumor, Brain and Nervous System, Eye and Orbit, Anus, Breast - Female, Breast - Male, Carcinoid Tumor, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Small Intestine, Soft Tissue
1. At least 18 years of age.
2. Ability to understand and the willingness to sign a written informed consent.
3. Newly diagnosed FIGO IVB cervical cancer with radiographic evidence of metastatic
disease for whom systemic therapy is standard of care, who are within 6 months of
systemic therapy treatment, OR
4. Patients with recurrent/metastatic disease with measurable disease in the pelvis for
whom systemic therapy is standard of care, who are within 6 months of systemic therapy
treatment.
5. Patients with brain metastasis are allowed as long as they are clinically stable
and/or the mets are treated or are amenable to treatment with radiation and/or
surgery.
6. Eastern Cooperative Group (ECOG) performance status of 0-3.
7. Women of child-bearing potential must agree to use adequate contraception (hormonal or
barrier method of birth control; abstinence) starting with the first radiation pulse
through 90 days after the last fraction of radiation. Should a woman become pregnant
or suspect she is pregnant while participating in this study, she should inform her
treating physician immediately. Medically acceptable birth control (contraceptives)
includes:
1) approved hormonal contraceptives (such as birth control pills, patch or ring;
Depo-Provera, Implanon), or 2) barrier methods (such as a condom or diaphragm) used with a
spermicide (a substance that kills sperm).
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)
Exclusion Criteria:
1. Prior radiation treatment to the pelvis.
2. Subjects may not be receiving any other investigational agents for the treatment of
the cancer under study.
3. Patients with active Inflammatory Bowel disease or Collagen vascular disease -SLE,
scleroderma or on active immunosuppressant (exclusions per PI discretion).
4. 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.
5. Subjects must not be pregnant or nursing due to the potential for congenital
abnormalities and the potential of this regimen to harm nursing infants.
6. Presence of brain metastases that are not amenable to treatment with radiation or
surgery, or brain metastasis leading to clinical instability.
Radiation: Ultra-fractionated radiation therapy
Cervical Cancer, Cervix, Stage IV Cervical Cancer FIGO 2018, Adenosquamous Carcinoma of Cervix, Metastasis
Cervix
UT Southwestern; Parkland Health & Hospital System
CD40 Agonist, Flt3 Ligand, and Chemotherapy in Triple Negative Breast Cancer
This research study is being done to find out if the immunotherapy drugs called CDX-301 and
CDX-1140 in combination with the standard chemotherapy treatment pegylated liposomal
doxorubicin (PLD, Doxil) are safe and effective at controlling the cancer in patients with
metastatic triple negative breast cancer, and to determine a safe dose and treatment schedule
of the three drugs. This research study will also test how these treatments improve your
body's immune response against the cancer.
• Unresectable Stage III or Stage IV Triple Negative Breast cancer
• Age 18 years or older
• Performance status ECOG 0-2
• Life expectancy ≥ 12 weeks
• Documented progressive disease, based on radiographic, clinical or pathologic
assessment, during or subsequent to last anticancer therapy.
• For initial safety cohort, subject is in second to third line setting of treatment for
metastatic or unresectable disease, and have received 1 to 2 prior regimens for
metastatic or unresectable disease. For dose expansion, subject is in first to third
line setting of treatment for metastatic or unresectable disease, and have received 0
to 2 prior regimens for metastatic or unresectable disease.
• Among any patient enrolled in the first line treatment setting, subjects must be PD-L1
negative by either SP142 or 22C3 assay and not be eligible for FDA approved standard
of care chemotherapy and anti-PD-1/PD-L1 combination therapy as alternative to this
clinical trial.
• Screening laboratory values must meet the following criteria
• Neutrophils ≥ 1500/uL
• Platelets ≥ 100 x109/L
• Hemoglobin ≥ 8 g/dL Patients may receive erythrocyte transfusions to achieve this
hemoglobin level at the discretion of the investigator. Initial treatment must
not begin earlier than the day after the erythrocyte transfusion.
• Creatinine ≤ 2 mg/dL
• Creatinine clearance >30 mL/minute
• AST ≤ 2.5 X ULN without, and ≤ 5 x ULN with hepatic metastasis
• ALT ≤ 2.5 X ULN without, and ≤ 5 x ULN with hepatic metastasis
• Total Bilirubin ≤ 1.5 X ULN (except patients with Gilbert's syndrome or liver
involvement, who must have a total bilirubin ≤ 2 X ULN)
• Alkaline phosphatase ≤ 2.5 X ULN without, and ≤ 5 x ULN with hepatic metastasis
• All men as well as women of child bearing potential enrolled in this trial must agree
to use effective contraception during the course of the trial and for at least 6
months after discontinuing study treatment. Patients and/or partners who are
surgically sterile or postmenopausal are exempt from this requirement.
• 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: ( 1) has not undergone a
hysterectomy or bilateral oophorectomy OR (2) 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).
• Provision of consent for pre-treatment and on-treatment biopsies. Biopsy sites must be
soft tissue tumor lesions or accessible visceral diseases that can be biopsied with
acceptable clinical risk (as judged by the investigator); are large enough to allow
for the collection of tumor tissue for proposed correlative studies (e.g., anticipated
goal of 6-8 cores preferred when feasible using a ≥ 18 gauge needle with an expected
core sample length of 5 mm); and have not been irradiated prior to entry. This does
not include bone lesions. This may exclude many lung lesions and small lesions.
• Measurable disease allowing for serial assessment of at least one target lesion(s) by
RECIST 1.1 criteria [100]. Target lesions selected for tumor measurements should be
those where additional (e.g., palliative) treatments are not indicated or anticipated.
• All residual toxicity related to prior anticancer therapies (excluding alopecia, grade
2 fatigue, vitiligo, endocrinopathies on stable replacement therapy, grade 2
neuropathy from taxanes or platinum and grade 2 hearing loss from platinum) must
resolve to grade 1 severity or less (or returned to baseline) prior to receipt of
study treatment.
• Read, understood, and provided written informed consent, and if applicable, Health
Insurance Portability and Accountability Act (HIPAA) authorization, after the nature
of the study has been fully explained, and must be willing to comply with all study
requirements and procedures.
Exclusion Criteria:
• Among any patients enrolled in the first line treatment setting, tumors should not be
PD-L1+ by SP142 or 22C3 assays (at least one of these assays must be checked by
treating physician per their preference) or eligible for FDA approved standard of care
chemotherapy and anti-PD-1/PD-L1 combination therapy as alternative to this clinical
trial.
• History of severe hypersensitivity reactions to mAbs.
• Prior treatment with any anti-CD40 antibody or rhuFlt3L product.
• Treatment with anthracycline in the metastatic setting.
• Prior progression while on anthracycline based therapy or within 6 months of
completing (neo)adjuvant chemotherapy regimen.
• Prior history of acute myeloid leukemia (AML), or tumor with known Flt3
mutation/amplification
• Receipt of any antibody targeting T cell check point or co-stimulation pathways within
4 weeks, use of any other monoclonal based therapies within 4 weeks, and all other
immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer)
within 2 weeks prior to the planned start of study treatment.
• Prior T-cell or other cell-based therapies within 12 weeks (or 2 weeks if patient
experienced disease progression on the prior treatment)
• Systemic radiation therapy within 4 weeks, prior focal radiotherapy within 2 weeks, or
radiopharmaceuticals (strontium, samarium) within 8 weeks prior to the first dose of
study treatment.
• Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to
the planned start of study treatment.
• Any kinase inhibitors within 2 weeks prior to the first dose of study treatment.
• Major surgery within 4 weeks prior to the first dose of study treatment. Surgery
requiring local/epidural anesthesia must be completed at least 72 hours before study
drug administration and patients should be recovered.
• Use of other investigational drugs within 4 weeks or 5 half-lives (whichever is
longer) prior to study treatment administration.
• Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within
2 weeks prior to first dose of study treatment. Topical, inhaled or intranasal
corticosteroids (with minimal systemic absorption) may be continued if the patient is
on a stable dose. Non-absorbed intraarticular corticosteroid and replacement steroids
(≤ 10 mg/day prednisone or equivalent) will be permitted.
• Other prior malignancy, except for adequately treated basal or squamous cell skin
cancer or in situ cancers; or any other cancer from which the patient has been
disease-free for at least 3 years.
• Active, untreated central nervous system metastases.
• Patients with known treated brain metastases should be neurologically stable for 4
weeks post-treatment and prior to study enrollment. Continued use of steroids and/or
anticonvulsants (in the absence of any suspicion of progressive brain metastases) is
acceptable if ≤ equivalent of prednisone 10 mg daily. Brain MRI required on screening
to document lack of progression.
• Women who are pregnant or nursing. All female patients with reproductive potential
must have a negative pregnancy test prior to starting treatment.
• Active autoimmune disease or a documented history of autoimmune disease, or history of
potential autoimmune syndrome that required systemic steroids or immunosuppressive
medications, except for patients with vitiligo, endocrinopathies, type 1 diabetes, or
patients with resolved childhood asthma/atopy or other syndromes which would not be
expected to recur in the absence of an external trigger (e.g., drug-related serum
sickness or post-streptococcal glomerulonephritis). Patients with mild asthma who
require intermittent use of bronchodilators (such as albuterol) who have not been
hospitalized for asthma in the preceding 3 years will not be excluded from this study.
• Significant cardiovascular disease including unstable angina pectoris, uncontrolled
hypertension or arrhythmia, congestive heart failure (New York Heart Association Class
III or IV or EF<50%) related to primary cardiac disease, uncontrolled ischemic or
severe valvular heart disease or any of the following within 6 months prior to the
first dose of study treatment: myocardial infarction, severe/unstable angina, coronary
artery bypass graft, congestive heart failure, cerebrovascular accident, transient
ischemic attack.
• Prior anthracycline therapy with a cumulative doxorubicin-equivalent dose greater than
240 mg/m2.
• Has received a live vaccine within 30 days prior to the first dose of study drug.
Examples of live vaccines include, but are not limited to the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
are generally killed virus vaccines and are allowed; however, intranasal influenza
vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. The
COVID-19 vaccines available in the United States are not live vaccines and are allowed
if the final vaccine dose (of a regimen that requires more than 1 dose) is received at
least 1 week prior to study enrollment.
• History of (non-infectious) pneumonitis or has current pneumonitis. This includes
asymptomatic infiltrates on screening chest CT scan that are suggestive of an
inflammatory process (i.e. grade 1 pneumonitis).
• Active infection requiring systemic therapy, known HIV infection, or positive test for
hepatitis B surface antigen or hepatitis C (antibody screen and if positive confirmed
by RNA analysis). If positive results are not indicative of a true active or chronic
infection, the patient can be enrolled after discussion with and agreement by the
Investigator.
• Any other acute or chronic medical or psychiatric condition or laboratory abnormality
that could increase the risk associated with trial participation or trial drug
administration or could interfere with the interpretation of trial results and, in the
judgment of the investigator, would make the patient inappropriate for entry into the
trial.
• Evidence of acute or chronic infection on screening chest radiography.
Research Study Looking at How Well Semaglutide Tablets Taken Once Daily Work in People Who Have a Body Weight Above the Healthy Range (OASIS 4)
This study will look how well semaglutide tablets taken once daily helps people with body
weight above the healthy range. Participants will either get semaglutide 25 milligram (mg)
once daily or placebo once daily. This study will last for 72 weeks, which includes 1-week
screening period, 64 weeks of treatment period and 7 weeks of follow up period.
• Informed consent obtained before any study-related activities. Study-related
activities are any procedures that are carried out as part of the study, including
activities to determine suitability for the study
• Male or female, age greater than or equal to 18 years at the time of signing informed
consent
• Body mass index (BMI) of
• Greater than or equal to 27.0 kg/m^2 with the presence of at least one of the
following weight-related complications (treated or untreated): hypertension,
dyslipidaemia, obstructive sleep apnoea or cardiovascular (CV) disease OR
• Greater than or equal to 30.0 kg/m^2
• History of at least one self-reported unsuccessful dietary effort to lose body weight
Exclusion Criteria:
• A self-reported change in body weight greater than 5 kg (11 pound [lbs]) within 90
days before screening irrespective of medical records
• HbA1c greater than or equal to 6.5 percent (48 mmol/mol) as measured by the central
laboratory at screening
The purposes of this project are 1) to compare the impact of maternal obesity versus
excessive gestational weight gain on obstructive sleep apnea (OSA) in obese and non-obese
women; 2) to investigate the mechanism(s) by which obesity and OSA increase cardiovascular
risk during pregnancy; and 3) to identify biomarker(s) for obesity-related OSA in pregnant
women.
• Both obese and non-obese (normal weight) early pregnant women aged ≥18 years old will
be permitted to participate in this project.
• No restriction with respect to race and socioeconomic status
• Women with a prior history of complicated pregnancy (i.e., gestational hypertension,
preeclampsia, HELLP syndrome, gestational diabetes, preterm birth, intrauterine growth
restriction, etc.) will be allowed to participate.
• Obese women with previously diagnosed OSA will be allowed to participate if they are
not currently on any recognized treatments such as Continuous Positive Airway Pressure
(CPAP), oral appliances or nasal expiratory positive airway pressure.
• Those who have had surgery for OSA in the past will be excluded.
• Women taking low-dose aspirin will be allowed to participate in this project.
Exclusion Criteria:
• Current multiple pregnancy;
• Known major fetal chromosomal or anatomical abnormalities;
• Recurrent miscarriage (three or more);
• Chronic essential hypertension (systolic BP >140 mmHg and/or diastolic BP >90 mmHg);
• Any evidence of cardiovascular and pulmonary diseases by history or by physical
examination;
• Kidney disease (serum creatinine >1.5 mg/dL);
• Coagulation disorders;
• Diabetes mellitus (fasting glucose ≥126 mg/dL or 2-hour oral glucose tolerance test
glucose level ≥200 mg/dL) or other systemic illness;
• Any evidence of neurological disease;
• Psychiatric disease or psychological disorders;
• History of drug or alcohol abuse within the last 2 years; and
• Given the effects of exercise training on sympathetic neural control,
endurance-trained athletes will be excluded. As this project focuses on sleep apnea in
pregnancy, Women with other significant sleep disorders such as restless legs syndrome
by Rest Leg Syndrome Diagnostic Index and insomnia by the Insomnia Severity Index or
Pittsburgh Sleep Quality Index will be excluded; In addition, women who report taking
a sleeping aid >1 time per month will be excluded.
A Study of ZN-c3 in Participants With Solid Tumors
studyfinder@utsouthwestern.edu
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT04158336
Show full eligibility criteria
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Key
Inclusion Criteria:
In order to be eligible to participate in any phase of this study, an individual must meet
all of the following criteria:
1. Provision of written informed consent.
2. Age ≥ 18 years or the minimum legal adult age (whichever is greater) at the time of
informed consent.
3. Adequate hematologic and organ function as defined by the following criteria:
1. 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.
2. Platelet count ≥ 100 × 10^9/L; excluding measurements obtained within 3 days
after transfusion of platelets.
3. 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.
4. Total serum bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN in the case of Gilbert's disease.
5. Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 60 mL/min.
4. Female subjects of childbearing potential must have a negative serum beta human
chorionic gonadotropin test.
5. 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:
1. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
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:
1. ECOG performance status ≤ 1.
2. 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:
1. ECOG performance status ≤ 1.
2. 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:
1. ECOG performance status ≤ 1.
2. Measurable disease per RECIST version 1.1.
Key
Exclusion Criteria:
1. Any of the following treatment interventions within the specified time frame prior to
Cycle 1 Day 1:
1. Major surgery within 28 days.
2. Radiation therapy within 21 days.
3. Any prior systemic therapy regardless of the stop date, but the subject must have
recovered to eligibility levels from prior toxicity.
4. Autologous or allogeneic stem cell transplant within 3 months.
5. 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).
2. A serious illness or medical condition(s) including, but not limited to, the
following:
1. Brain metastases that require immediate treatment or are clinically or
radiologically unstable.
2. Leptomeningeal disease that requires or is anticipated to require immediate
treatment.
3. Myocardial impairment of any cause resulting in heart failure by New York Heart
Association Criteria Class III or IV.
4. 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.
5. Significant gastrointestinal abnormalities
6. Active or uncontrolled infection.
3. Unresolved toxicity of Grade > 1 attributed to any prior therapies (excluding Grade 2
neuropathy, alopecia or skin pigmentation).
4. Prior therapy with ZN-c3 or known hypersensitivity to any drugs similar to ZN-c3 in
class.
5. 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, Peritoneal Cancer