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.
Peri-Operative Ipilimumab+Nivolumab and Cryoablation in Women With Triple-negative Breast Cancer
The purpose of this study is to determine the impact of pre-operative cryoablation,
ipilimumab and nivolumab on on 3-year Event Free Survival (EFS), in women with residual
hormone receptor negative, HER2-negative ("triple negative") resectable breast cancer after
taxane-based neoadjuvant chemotherapy.
• Women age 18 years or older
• Confirmed histologic diagnosis of invasive carcinoma of the breast
• Pathology confirmation of invasive carcinoma (reported or requested and pending)
• ER, PR and HER2 negative on outside or Cedars Sinai biopsy report, where ER and PR
negative are defined as staining present in ≤10% of invasive cancer cells by IHC, and
HER2-negative is defined as IHC 0-1+ or FISH <2.0. If ER, PR and HER2 status are not
reported the results must be requested and pending.
• Operable tumor measuring ≥1.0 cm in maximal diameter
• Any nodal status
• Multifocal and multicentric disease is permitted.
• Synchronous bilateral invasive breast cancer is permitted
• No indication of distant metastases
• Total mastectomy or lumpectomy planned
• Tumor amenable to cryoablation as determined by a study radiologist
• ECOG performance status score of 0 or 1.
• Screening laboratory values must meet the following criteria:
• White blood cells (WBCs) ≥ 2000/μL
• Absolute neutrophil count (ANC) ≥ 1500/μL
• Platelets ≥ 100 x 103/μL ii. Hemoglobin ≥ 9.0 g/dL iii. Serum creatinine ≤ 1.5 x ULN
or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula
below): Female CrCl = (140 •age in years) x weight in kg x 0.85 72 x serum creatinine
in mg/dL
• AST/ALT ≤ 3 x upper limit of normal (ULN)
• Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert's syndrome, who must have total
bilirubin < 3.0 mg/dL)
• No history of known HIV
• No history of known active hepatitis B or hepatitis C
• Women of childbearing potential** (WOCBP) must use appropriate method(s) of
contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30
days plus the time required for nivolumab and ipilimumab to undergo five half-lives)
after the last dose of investigational drug
• Women of childbearing potential must have a negative serum or urine pregnancy test
(minimum sensitivity 25 IU/L or equivalent units of HCG)
• Women must not be breastfeeding
• Willing to adhere to the study visit schedule and the prohibitions and restrictions
specified in this protocol.
• Prior checkpoint blockade administration is permitted with a washout period of 3 weeks
• "Women of childbearing potential" is defined as any female who has experienced
menarche and who has not undergone surgical sterilization (hysterectomy or
bilateral oophorectomy) or who is not postmenopausal. Menopause is defined
clinically as 12 months of amenorrhea in a woman over 45 in the absence of other
biological or physiological causes.
Women of childbearing potential (WOCBP) receiving nivolumab and ipilimumab will be
instructed to adhere to contraception for a period of 23 weeks after the last dose of
investigational product. Men receiving nivolumab and who are sexually active with WOCBP
will be instructed to adhere to contraception for a period of 31 weeks after the last dose
of investigational product. These durations have been calculated using the upper limit of
the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP
use contraception for 5 half-lives plus 30 days and men who are sexually active with WOCBP
use contraception for 5 half-lives plus 90 days.
Exclusion Criteria:
• Medical history and concurrent diseases
• Has an 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). Note: Replacement therapy (eg, thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency) is not considered a form of systemic treatment.
• Any underlying medical or psychiatric condition, which in the opinion of the
investigator, will make the administration of study drug hazardous or obscure the
interpretation of AEs, such as a condition associated with frequent or poorly
controlled diarrhea.
• Prohibited Treatments and/or Therapies
• Chronic use of immunosuppressants and/or systemic corticosteroids (used in the
management of cancer or non-cancer-related illnesses). Brief periods of steroid
use, for example for the management of chemotherapy-associated toxicities, are
allowed. The use of corticosteroids on study is allowed for the treatment of
immune related adverse events (irAEs) and other medical conditions including
adrenal insufficiency.
• Any non-oncology live vaccine therapy used for prevention of infectious diseases
within 3 weeks prior to first dose of ipilimumab.
• Prior investigational agents within 3 weeks prior to ipilimumab/nivolumab
Drug: Ipilimumab, Drug: Nivolumab, Procedure: Core Biopsy/Cryoablation, Procedure: Breast Surgery
Breast Cancer, Breast - Female
Hormone Receptor Negative, Her2- Negative, Resectable Breast Cancer, breast cancer, immunotherapy, Ipilimumab, Nivolumab, Cryoablation
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
A Phase I Dose Escalation Study of Single Fraction Ablative Pre-operative Partial Breast (S-PBI) for Early Stage Breast Cancer
The purpose of this phase I trial is to evaluate dose-limiting toxicity while dose escalating
single-fraction preoperative S-PBI to a presumed radioablative dose over 3 cohorts, starting
with 30Gy in 1 fraction and advancing to 34Gy and 38Gy in 1 fraction.
1. Invasive epithelial (ductal, medullary, lobular, papillary, mucinous (colloid), or
tubular) histologies of the breast 3 cm or less(T1-T2cN0) in women who have not
undergone surgery or neoadjuvant endocrine or chemotherapy for current breast cancer
diagnosis
2. Tumor must not involve the overlying skin based on imaging evaluation and/or clinical
exam
3. Age >/= 18 years old and female
4. Greatest Tumor dimension is 3cm or less based on US. MRI measurements can be included
only if performed BEFORE the biopsy
5. Tumor must be unifocal
6. The tumor must be visible on CT scan and/or preferably marked with clip(s) in tumor
7. Patients must undergo an MRI for work up to aid in tumor delineation and to rule out
additional foci of disease. If additional foci of disease are present, they need to
have a negative biopsy to proceed with treatment.If patient cannot have MRI, contrast
enhanced digital mammography (CEDM) is allowed in place of MRI.
8. Clinically and radiographically node negative on ultrasound of the axilla or MRI
9. Estrogen receptor positive or Progesterone receptor positive and Her2neu negative
10. Ability to understand and the willingness to sign a written informed consent.
11. Women of child-bearing potential must agree to use adequate contraception (hormonal or
barrier method of birth control) prior to the start of study and for the duration of
radiation therapy. 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, 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. Multi-centric disease
2. Prior RT to the involved breast
3. Tumor size >3cm
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. Patients who are pregnant or lactating due to the potential exposure to the fetus to
radiation therapy and unknown effects of radiation therapy to lactating females
6. Patients unable to have an MRI or contrast enhanced digital mammography (CEDM)
7. Prior ipsilateral breast cancer
8. Tumor less than 5mm from the skin surface on clinical exam and/or radiographic imaging
9. Patients with active Lupus or scleroderma
Single Cell Immune and Non-immune Correlates of Response to Neoadjuvant Abemaciclib
The purpose of this study is to better understand how the immune system plays a role in
fighting breast cancer and specifically research if the immune system response against breast
cancer can be improved with endocrine therapy and cyclin dependent kinase inhibitor therapy
in patients with hormone receptor positive breast cancer. This will be studied by collecting
tumor tissue and blood samples before and after 2 weeks of study treatment with commonly used
endocrine therapy and cyclin dependent kinase inhibitor therapy.
INCLUSION CRITERIA:
• Clinical stage operable stage I, II, or III invasive mammary carcinoma, which is
estrogen receptor or progesterone receptor positive by immunohistochemistry and HER2
negative by Herceptest (0 or 1+) or not amplified by in situ hybridization as per
routine clinical testing.
• Have post-menopausal status, as defined by any of the following: Subjects at least 55
years of age OR Subjects under 55 years of age and amenorrheic for at least 12 months
OR follicule stimulating hormone (FSH) values ≥ 40 IU/L and estradiol levels ≤ 40
pg/mL (140 pmol/L) or in postmenopausal ranges per local or institutional reference
ranges.
• Breast tumor ≥1cm in diameter by either physical exam or ultrasound and suitable for
pre and post-treatment tissue sampling.
• Meet either of 2 following criteria, for which neoadjuvant endocrine therapy for 2
weeks is deemed suitable: 1) disease that is planned for surgery as initial therapy,
in which 2 weeks of neoadjuvant endocrine therapy is deemed suitable, 2) Disease for
which neoadjuvant systemic therapy (either chemotherapy or endocrine therapy) may be
planned, in which 2 weeks of neoadjuvant endocrine therapy prior to start of systemic
therapy is deemed suitable.
• At least 18 years of age
• Performance status ECOG ≤ 2
• Have adequate organ function (ANC ≥1,500/mcL, Platelets ≥100,000/mcL, Hemoglobin ≥8
g/dL, Total bilirubin ≤1.5 × upper limit of normal, ALT and AST ≤3 × upper limit of
normal, Creatinine clearance >30 mL/minute
• The patient is able to swallow oral medications
• Patients with a prior history of contralateral breast cancer are eligible if they have
no evidence of recurrence of their initial primary breast cancer.
• Women may have been taking tamoxifen or raloxifene as a preventive agent prior to
study entry but must have discontinued the drug for at least 28 days prior to study
enrollment.
• Subjects have ended hormone replacement therapy at least 7 days prior to receiving the
first dose of randomized therapy.
• Ability to understand and the willingness to sign a written informed consent.
• A female of childbearing potential, must have a negative serum pregnancy test within 7
days of the first dose of abemaciclib and agree to use a highly effective
contraception method during the treatment period and for 3 weeks following the last
dose of abemaciclib. These criteria should not apply to most or all patients on the
trial given the inclusion criteria is for post-menopausal patients only who should not
be of childbearing potential.
Note: Contraceptive methods may include an intrauterine device [IUD] or barrier method. If
condoms are used as a barrier method, a spermicidal agent should be added as a double
barrier protection. Cases of pregnancy that occur during maternal exposures to abemaciclib
should be reported. If a patient or spouse/partner is determined to be pregnant following
abemaciclib initiation, she must discontinue treatment immediately. Data on fetal outcome
and breast-feeding are to be collected for regulatory reporting and drug safety evaluation.
EXCLUSION CRITERIA:
• Active metastatic breast cancer, inflammatory breast cancer, or locally recurrent
breast cancer.
• The patient has serious and/or uncontrolled preexisting medical condition(s) that, in
the judgment of the investigator, would preclude participation in this study (for
example, interstitial lung disease, severe dyspnea at rest or requiring oxygen
therapy, severe renal impairment [e.g. estimated creatinine clearance <30ml/min],
history of major surgical resection involving the stomach or small bowel, or a
preexisting chronic condition resulting in baseline grade 2 or higher diarrhea).
• Females who are pregnant, lactating, or premenopausal.
• Severe uncontrolled malabsorption condition or disease (i.e. grade 2 or higher
diarrhea, severe malnutrition, short gut syndrome).
• Dementia, altered mental status, or any psychiatric condition that would prohibit the
understanding or rendering of informed consent.
• Chemotherapy, radiotherapy, or any other cancer therapy for current diagnosis of
breast cancer.
• Subjects may not have received or be receiving any other investigational agents for
the treatment of the cancer under study.
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to abemaciclib or other agents used in study.
• 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.
Drug: Letrozole, Drug: Abemaciclib
Breast Cancer, Breast - Female
UT Southwestern; Parkland Health & Hospital System
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
Regional Radiotherapy in Biomarker Low-Risk Node Positive and T3N0 Breast Cancer (TAILOR RT)
The purpose of this study is to compare the effects on low risk breast cancer receiving usual
care that includes regional radiation therapy, with receiving no regional radiation therapy.
Researchers want to see if not giving this type of radiation treatment works as well at
preventing breast cancer from coming back.
• Patients must be women with newly diagnosed histologically proven invasive carcinoma
of the breast with no evidence of metastases, staged as per site standard of care.
• Patients must have been treated by BCS or mastectomy with clear margins of excision.
Post-mastectomy positive margins for invasive disease and/or DCIS is not allowed.
Multifocal disease (i.e. the presence of two or more foci or breast cancer within the
same breast quadrant) and multicentric disease (i.e. the presence of two or more foci
of breast cancer in different quadrants of the same breast) are allowed.
• Patients with T3N0 disease are eligible.
• Patients with disease limited to nodal micrometastases are eligible
• Patients with nodal macrometastases (>2mm) treated by axillary dissection must have
1-3 positive axillary nodes (macrometastases, > 2 mm).
• Patients treated by mastectomy and SLNB alone must have only 1-2 positive axillary
nodes (macrometastases, > 2 mm).
• Patients must be ER ≥ 1% and HER2 negative on local testing
• Patients must have an Oncotype DX recurrence score ≤25 obtained from testing of breast
tumour tissue from a core biopsy or from the surgical specimen.
• Patient must consent to provision of, and investigator(s) must agree to submit to the
CCTG Central Tumour Bank, a representative formalin fixed paraffin block of tumour
tissue in order that the specific correlative marker assays described in the protocol
may be conducted
• Patient must consent to provision of samples of blood in order that the specific
correlative marker assays described in the protocol may be conducted.
• Patients must have had endocrine therapy initiated or planned for ≥ 5 years.
Premenopausal women will receive ovarian ablation plus aromatase inhibitor therapy or
tamoxifen if adjuvant chemotherapy was not administered. For all patients, endocrine
therapy can be given concurrently or following RT.
• Patients may or may not have had adjuvant chemotherapy.
• RT must commence within 16 weeks of definitive surgery if the patient is not treated
with chemotherapy. If adjuvant chemotherapy is given, RT must begin within 12 weeks
after the last dose. (Note: adjuvant chemotherapy may be ongoing at the time of
randomization). Definitive surgery is defined as the last breast cancer-related
surgery.
• Patient's ECOG performance status must be 0, 1 or 2.
• Patient's age must be ≥ 35 years.
• For the first 736 eligible English or French-speaking subjects who have agreed to
optional questionnaire completion: Patient is able (i.e. sufficiently fluent) and
willing to complete the quality of life, health utilities and lost productivity
questionnaires in either English or French (note: enrollment completed 2022Aug02)
• Patient consent must be appropriately obtained in accordance with applicable local and
regulatory requirements
• Patients must be accessible for treatment and follow-up. Investigators must assure
themselves the patients randomized on this trial will be available for complete
documentation of the treatment, adverse events, and follow-up.
• In accordance with CCTG policy, protocol treatment is to begin within 6 weeks of
patient randomization.
• Women of childbearing potential must have agreed to use an effective contraceptive
method. A woman is considered to be of "childbearing potential" if she has had menses
at any time in the preceding 12 consecutive months.
Exclusion Criteria:
• Patients with nodal disease limited to isolated tumour cells (pN0i+ < 0.2 mm).
• Patients with pT3N1 and pT4 disease (Note: patients with T3N0 are eligible).
• Any prior history, not including the index cancer, of ipsilateral invasive breast
cancer or ipsilateral DCIS treated with radiation therapy. (Patients with synchronous
or previous ipsilateral LCIS are eligible.)
• Synchronous or previous contralateral invasive breast cancer. (Patients with
contralateral DCIS are eligible unless previously treated with radiation.)
• History of non-breast malignancies except adequately treated non-melanoma skin
cancers, in situ cancers treated by local excision or other cancers curatively treated
with no evidence of disease for ≥ 5 years.
• Patients who are pregnant.
• Patients that have had prior ipsilateral chestwall/thoracic radiation.
• Patients treated with chemo or endocrine therapy administered in the neoadjuvant
setting for breast cancer. Endocrine therapy exposure 12 weeks or less prior to
surgery is permitted.
• Patients with serious non-malignant disease (e.g. cardiovascular, scleroderma etc.)
which would preclude RT.
• Patients with any serious active or co-morbid medical conditions, laboratory
abnormality, psychiatric illness, active or uncontrolled infections, or serious
illnesses or medical conditions that would prevent the patient from participating or
to be managed according to the protocol (according to investigator's decision).
Radiation: Radiation, Other: No Radiation
Breast Cancer, Breast - Female
UT Southwestern; Parkland Health & Hospital System
This is an early research and development study. The objective of this study is to determine
the feasibility of the Imagio OA/US Breast Imaging System to detect complete breast cancer
pathologic response to neoadjuvant therapy as assessed by functional optoacoustic features,
vascular features and relative degrees of oxygenation/deoxygenation
1. 18 years and older male or female patients;
2. Ipsilateral intact biopsy-proven invasive breast cancer clinical T1-T4 (by standard of
care imaging), including primary or recurrent disease.
3. Patient eligible to receive neoadjuvant chemotherapy
Exclusion Criteria:
1. Known Stage IV disease (breast or other cancer);
2. Have a condition or impediment (i.e., insect bites, poison ivy, open sores, chafing of
the skin, scar, tattoos, moles, etc.); that could interfere with the intended field of
view (within one probe length or 4 cm of the nodule);
3. Patient has received chemotherapy for any type of cancer within 90 days from date of
baseline Imagio OA/US exam;
4. Is experiencing photo-toxicity associated with currently taking, or having taken,
photosensitizing agents within the previous 72 hours such as sulfa, ampicillin,
tetracycline;
5. Is currently undergoing phototherapy;
6. Has a history of any photosensitive disease (e.g., porphyria, lupus erythematosus);
7. Is undergoing treatment for a photosensitive disease and is experiencing
photosensitivity;
8. Pregnancy;
9. Patient has participated in a clinical study of an investigational drug or device
within 3 months prior to screening visit that may have an impact on clinical outcomes.
Device: Imagio OA/US
Breast Cancer, Breast - Female, Breast - Male
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.
Safety and Feasibility of Robotic SP Nipple Sparing Mastectomy
This is a single arm, single-center, prospective clinical trial designed to track the peri,
post-operative and oncologic outcomes when utilizing the da-Vinci single port (SP) robotic
platform to perform robotic nipple sparing mastectomy (rNSM) and immediate breast
reconstruction with tissue expanders/implants and acellular dermal matrix (ADM - Alloderm),
for patients with breast cancer as well as those with a high risk for breast cancer.
Safety and feasibility measures will be measured as primary outcome measures. Oncological and
patient satisfaction outcome measures will be measured. Our hypothesis is that SPr-NSM is
equal to open NSM in terms of safety, feasibility and oncological outcomes with improved
patient satisfaction as measured by nipple sensation and patient reported outcomes.
• Candidates for open nipple sparing mastectomy, per standard of care with regards to
anatomic factors and tumor location including: nipple sparing resection and resection
OR prophylactic mastectomy for risk reduction OR treatment of ductal carcinoma in-situ
or clinically node negative cT1-T3 breast cancer
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Exclusion Criteria:
• Inability to provide informed consent
• Pregnant or nursing women
• Patients with:
• Inflammatory breast cancer
• Skin involvement with tumor
• Pre-operative diagnosis of Nipple Areolar Complex (NAC) tumor involvement
• Grade 3 or higher nipple ptosis
• Contraindicated for general anesthesia or surgery
• Heavy current smoking history (defined as > 20 cigarettes per day)
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
Neoadjuvant Her2-targeted Therapy and Immunotherapy With Pembrolizumab
A phase 2 open-label, randomized, multi-center trial to evaluate the efficacy and safety of
neoadjuvant trastuzumab, pertuzumab and weekly paclitaxel (THP) as compared to neoadjuvant
trastuzumab, pertuzumab, pembrolizumab and weekly paclitaxel (THP-K), or neoadjuvant
trastuzumab, pembrolizumab and weekly paclitaxel (TH-K) in chemo naive patients with invasive
human epidermal growth factor receptor 2 (HER2) positive breast cancer whose primary tumors
are > 2 cm and/or clinically lymph node positive. Treatment will be followed by standard of
care breast surgery and physician's choice adjuvant therapy per standard of care.
1. Male/female patients with histologically confirmed invasive HER2-positive (by American
Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines)
unilateral breast cancer
2. Have previously untreated non-metastaic (M0), cT2-4N0 or cT1-4N1-3 (biopsies of
clinically suspicious lymph nodes to confirm nodal status is encouraged).
3. Multifocal/centric disease is permitted if all suspicious foci have been biopsied and
are consistent with HER2-positive (by ASCO/CAP guidelines) invasive breast cancer
4. Be a male or female subject 18 years of age on the day of signing informed consent
5. Male Participants: A male participant must agree to use a contraception as detailed in
Appendix C of this protocol during the treatment period and for at least 6 months
after the last dose of study treatment and refrain from donating sperm during this
period.
6. Female Participants: A female participant is eligible to participate if she is not
pregnant (see Appendix C), not breastfeeding, and at least one of the following
conditions applies: a.) Not a woman of childbearing potential (WOCBP) as defined in
Appendix C OR b.) A WOCBP who agrees to follow the contraceptive guidance in Appendix
C during the treatment period and for at least 6 months after the last dose of study
treatment.
7. The participant (or legally acceptable representative if applicable) provides written
informed consent for the trial.
8. Provides adequate archival tumor tissue sample or newly obtained core or excisional
biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded
(FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to
archived tissue. Note: If submitting unstained cut slides, newly cut slides should be
submitted to the testing laboratory within 14 days from the date slides are cut.
9. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
10. Have adequate organ function as defined by the following parameters. Specimens must be
collected within 7 days prior to the start of study treatment.
• Absolute neutrophil count (ANC) ≥1500/µL
• Platelets ≥100 000/µL
• Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La
• Renal Creatinine (≤1.5 × ULN OR) OR Measured or calculated(b) creatinine
clearance (≥30 mL/min for participant with creatinine levels) (GFR can also be
used in place of creatinine or CrCl) (>1.5 × institutional ULN)
• Hepatic Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with
total bilirubin levels >1.5 × ULN aspartate aminotransferase (AST, SGOT) and
alanine aminotransferase (ALT, SGPT) ≤2.5 × ULN (≤5 × ULN for participants with
liver metastases)
• Coagulation International normalized ratio (INR) OR prothrombin time (PT)
Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is
receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range
of intended use of anticoagulants
• Cardiac Echocardiogram or MUGA (multigated radionuclide angiography) Baseline
LVEF ≥ 55%
Exclusion Criteria:
1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to
randomization. If the urine test is positive or cannot be confirmed as negative, a
serum pregnancy test will be required. Note: in the event that 72 hours have elapsed
between the screening pregnancy test and the first dose of study treatment, another
pregnancy test (urine or serum) must be performed and must be negative in order for
subject to start receiving study medication.
2. Has received prior therapy with an anti-PD-1 (programmed death protein 1), anti-PD-L1
(Programmed death-ligand 1), or anti PD L2 (Programmed death-ligand 2) agent or with
an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,
CTLA-4, OX 40, CD137).
3. Has received prior systemic anti-cancer therapy including investigational agents
within 4 weeks prior to randomization. Note: If participant received major surgery,
they must have recovered adequately from the toxicity and/or complications from the
intervention prior to starting study treatment.
4. Has received prior radiotherapy within 2 weeks of start of study treatment.
Participants must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis.
5. 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 (eg, FluMist®) are live attenuated vaccines and are not allowed.
6. Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose of
study treatment.
Note: Participants who have entered the follow-up phase of an investigational study
may participate as long as it has been 4 weeks after the last dose of the previous
investigational agent.
7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study drug.
8. Has a known additional malignancy that is progressing or has required active systemic
treatment within the past 3 years. Note: Participants with basal cell carcinoma of the
skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast
carcinoma, cervical cancer in situ) that have undergone potentially curative therapy
are not excluded.
9. Has 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 (eg., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.
10. Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.
11. Has an active infection requiring systemic therapy.
12. Has a known history of Human Immunodeficiency Virus (HIV).
13. Has a known active Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or Hepatitis C virus (i.d. HCV RNA [qualitative] is detected) infection.
14. Has a known history of active TB (Bacillus Tuberculosis).
15. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the subject's
participation for the full duration of the study, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
16. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
17. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of trial treatment.
18. Has significant cardiovascular disease, such as:
• History of myocardial infarction, acute coronary syndrome or coronary
angioplasty/stenting/bypass grafting within the last 6 months
• Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV or
history of CHF NYHA class III or IV
• Angina pectoris requiring anti-anginal medication, uncontrolled arrhythmias, or
uncontrolled hypertension (systolic blood pressure > 180mmHg and/or diastolic
blood pressure > 100mmHg).
CompassHER2-pCR: Decreasing Chemotherapy for Breast Cancer Patients After Pre-surgery Chemo and Targeted Therapy
This trial studies how well paclitaxel, trastuzumab, and pertuzumab work in eliminating
further chemotherapy after surgery in patients with HER2-positive stage II-IIIa breast cancer
who have no cancer remaining at surgery (either in the breast or underarm lymph nodes) after
pre-operative chemotherapy and HER2-targeted therapy. Drugs used in chemotherapy, such as
paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the
cells, by stopping them from dividing, or by stopping them from spreading. Trastuzumab and
pertuzumab are both a form of "targeted therapy" because they work by attaching themselves to
specific molecules (receptors) on the surface of tumor cells, known as HER2 receptors. When
these drugs attach to HER2 receptors, the signals that tell the cells to grow are blocked and
the tumor cell may be marked for destruction by the body's immune system. Giving paclitaxel,
trastuzumab, and pertuzumab may enable fewer chemotherapy drugs to be given without
compromising patient outcomes compared to the usual treatment.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0 or 1
• Patient must have histologically confirmed HER2-positive primary invasive breast
carcinoma, determined by local testing. The tumor must have either HER2 IHC result of
3+ or HER2/CEP17 ratio > 2 with > 4.0 HER2 signals per cell by ISH. Tumors with
HER2/CEP17 ISH ratio < 2 are ineligible, even if HER2 copy number is > 6, unless HER2
IHC result is 3+.
• Patients hormone receptor (estrogen receptor [ER] and progesterone receptor [PR])
status must be known and will be determined by local testing. Patients with either
hormone receptor -positive or hormone receptor- negative HER2-positive breast cancer
are eligible
• Patients must have AJCC 8th Edition stage II or IIIa according to anatomic staging
table at diagnosis
• Patients without nodal involvement (cN0) are eligible if T size > 2.0 cm (T2-3)
• Patients with nodal involvement (cN1-2) are eligible if T1-3
• Patients with clinical T4 or N3 disease are not eligible
• Patient must be willing and able (i.e., have no contraindication) to receive standard
adjuvant therapy, consisting of HER2-directed therapy, radiation (if indicated) and
endocrine therapy (if ER+) if achieving pCR at surgery
• Patient with bilateral invasive breast cancers are eligible if both cancers are
HER2-positive (as defined in 3.1.3) at least one meets protocol eligibility and
neither cancer renders the patient ineligible (i.e. per eligibility 3.1.5)
• Patients with multiple ipsilateral invasive tumors are eligible as long as all tumors
are HER2-positive, and at least one tumor focus meets eligibility criteria (per
eligibility 3.1.5). Multiple lesions that appear part of the same index tumor do not
require additional biopsy/HER2 testing. Multiple lesions that appear part of the same
index tumor do not require additional biopsy/HER2 testing. However, even if biopsy is
not deemed necessary, consideration should be given to placing a clip in any lesion
that is 1 cm or further from the primary tumor to ensure that all tumor is removed at
surgery AND that the pathologist can locate all primary sites of tumor to assess
pathologic response at surgery.
• Patients with a history of other non-breast malignancies are eligible if they have
been disease-free for at least 5 years, and are deemed by the investigator to be at
low risk for recurrence of that malignancy.
• Patients with the following cancers are eligible if diagnosed and treated within
the past 5 years: cervical cancer in situ, basal cell or squamous cell carcinoma
of the skin, and localized papillary or follicular thyroid cancer who have
completed recommended treatment including surgery. Patients with any other
cancers within the last 5 years are ineligible.
• Patents must have a left ventricular ejection fraction (LVEF) within normal
institutional parameters (or > 50%)
• Patients must not have > grade 1 peripheral neuropathy of any etiology.
• Patients must have a bilateral mammogram and a diagnostic breast ultrasound [on the
side of the cancer(s)] (with or without breast MRI) performed at screening. An
axillary ultrasound on the side of the cancer(s) is also required. However, if a
patient has a negative axillary physical exam and a baseline MRI without suspicious
lymph nodes performed before axillary ultrasound, axillary ultrasound may be omitted.
Comprehensive breast and axillary imaging must be performed within 42 days of
registration (i.e. the patient's mammogram/ breast ultrasound /axillary ultrasound OR
their breast MRI).
• Baseline imaging of the ipsilateral axilla by ultrasound or breast MRI is mandatory.
For subjects with axillary lymph node(s) suspicious on clinical exam or imaging,
patient must be willing to have a needle aspiration or core biopsy to determine the
presence of metastatic disease in the lymph nodes. A clip must be placed in the
involved axillary lymph node. (If there are more than 1 suspicious axillary nodes,
only one clipped node is required).
• Patient of childbearing potential and sexually active patients must use accepted and
effective method(s) of contraception or to abstain from sexual intercourse for the
duration of their participation in the study and for 7 months after the last dose of
study treatment.
• Patient must be willing and able to sign informed consent
• Leukocytes >= 3,000/mcL (obtained =< 28 days prior to protocol registration)
• Absolute neutrophil count >= 1,500/mcL (obtained =< 28 days prior to protocol
registration)
• Platelets >= 100,000/mcL (obtained =< 28 days prior to protocol registration)
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (obtained =< 28
days prior to protocol registration)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 x institutional ULN (obtained =< 28 days prior to protocol registration)
• Creatinine =< 1.5 x institutional ULN (obtained =< 28 days prior to protocol
registration)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
Exclusion Criteria:
• Patients must not have impaired decision-making capacity
• Patient must not have a history of any prior (ipsilateral or contralateral) invasive
breast cancer
• One exception: a patient with a history of T1N0 triple negative breast cancer
diagnosed more than 10 years earlier, who remains disease free is eligible
• Patient must not have prior ipsilateral ductal breast carcinoma in situ (DCIS).
Patients with prior lobular breast carcinoma in situ (LCIS), atypical hyperplasia,
other high risk benign lesions or contralateral DCIS (without evidence of
microinvasion) are eligible
• NOTE: Patients currently receiving endocrine therapy for prior contralateral DCIS
are eligible
• Patient must not have stage IV (metastatic) breast cancer
• Staging studies (computed tomography [CT] chest/abdomen/pelvis and a bone scan or
positron emission tomography [PET]-CT scan) are required for stage III disease or
those with abnormal baseline liver function tests (LFTs), symptoms (e.g. new bone
pain) or abnormal physical exam findings (National Comprehensive Cancer Network
[NCCN] guidelines version [V]1.2019)
• Patient must not have T4 and/or N3 disease, including inflammatory breast cancer
• Patient must not have any prior treatment for the current breast cancer, including
surgery, chemotherapy, hormonal therapy, radiation or experimental therapy
• Patients must not have > grade 1 peripheral neuropathy of any etiology
• Patient must not have a concurrent serious medical condition that would preclude
completion of study therapy. For example, uncontrolled hypertension (systolic > 180 mm
Hg and/or diastolic > 100 mm Hg) or clinically significant (i.e. active)
cardiovascular disease: cerebrovascular accident/stroke or myocardial infarction
within 6 months prior to registration, unstable angina, congestive heart failure (CHF)
or serious cardiac arrhythmia requiring medication and other concurrent serious
diseases that may interfere with planned treatment
• Patient must not be pregnant or breast-feeding due to the potential harm to an unborn
fetus and possible risk for adverse events in nursing infants with the treatment
regimens being used. Patients must also not expect to conceive from the time of
registration, while on study treatment, and until at least 7 months after the last
dose of study treatment. All patients of childbearing potential must have a blood test
or urine study within 14 days prior to registration to rule out pregnancy
• All patients of childbearing potential is anyone, regardless of sexual
orientation or whether they have undergone tubal ligation, who meets the
following criteria: 1) has achieved menarche at some point, 2) has not undergone
a hysterectomy or bilateral oophorectomy; or 3) has not been naturally
postmenopausal for at least 24 consecutive months (i.e., has had menses at any
time in the preceding 24 consecutive months)
Invasive Breast Carcinoma, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8, Anatomic Stage IIB Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Prognostic Stage II Breast Cancer AJCC v8, Prognostic Stage IIA Breast Cancer AJCC v8, Prognostic Stage IIB Breast Cancer AJCC v8, Prognostic Stage IIIA Breast Cancer AJCC v8, Breast - Female, Breast - Male
UT Southwestern; Parkland Health & Hospital System
Optimizing the Use of Ketamine to Reduce Chronic Postsurgical Pain (KALPAS)
The study utilizes a 3-arm placebo-controlled RCT to study the effectiveness of ketamine in
reducing chronic post-mastectomy pain. Participants randomized to the first arm will receive
a 0.35 mg/kg dose after induction, followed by a 0.25 mg/kg/hr infusion during surgery (up to
a maximum of 6 hours) and continued for 2 hours postoperatively. Participants in the second
arm will receive a single dose of 0.6 mg/kg of ketamine in the post-anesthesia care unit, and
the final group will serve as the control group and receive saline (no ketamine).
• Woman 18 years of age or older
• Undergoing elective breast surgery for oncologic indication as follows: unilateral or
bilateral mastectomy, prophylacticmastectomy, +/- lymph node dissection, +/- immediate
or delayed reconstruction.
• No distant metastases
Exclusion Criteria:
• History of cognitive impairment or clinical signs of altered mental status (AMS) that
may interfere with adherence to study procedures and/or participant safety. Clinical
signs of AMS may include but are not limited to: confusion, amnesia, disorientation,
fluctuating levels of alertness, etc.
• Past ketamine or phencyclidine misuse or abuse
• Schizophrenia or history of psychosis
• History of post-traumatic stress disorder
• Known sensitivity or allergy to ketamine
• Liver or renal insufficiency
• History of uncontrolled hypertension, chest pain, cardiac arrhythmia, stroke, head
trauma, intracranial mass or hemorrhage, glaucoma, porphyria, uncontrolled thyroid
disease, or other contraindication to ketamine
• Lamotrigine, alfentanil, physostigmine, or 4-aminopyridine use
• Currently Pregnant
• Body mass index (BMI) greater than 35
• Non-English or non-Spanish speaker
• Currently participating in another pain interventional trial
• Unwilling to comply with all study procedures and be available for the duration of the
study
• Patient is American Society of Anesthesiologists (ASA) physical status 4, 5, or 6
• Patient has started or undergone hormone therapy for gender transition into male.
• Patient scheduled for any bilateral (or greater) flap reconstruction
T-DM1 and Tucatinib Compared With T-DM1 Alone in Preventing Relapses in People With High Risk HER2-Positive Breast Cancer, the CompassHER2 RD Trial
This phase III trial studies how well trastuzumab emtansine (T-DM1) and tucatinib work in
preventing breast cancer from coming back (relapsing) in patients with high risk, HER2
positive breast cancer. T-DM1 is a monoclonal antibody, called trastuzumab, linked to a
chemotherapy drug, called DM1. Trastuzumab is a form of targeted therapy because it attaches
to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors,
and delivers DM1 to kill them. Tucatinib may stop the growth of tumor cells by blocking some
of the enzymes needed for cell growth. Giving T-DM1 and tucatinib may work better in
preventing breast cancer from relapsing in patients with HER2 positive breast cancer compared
to T-DM1 alone.
• HER2-positive status will be based on pretreatment biopsy material and defined as an
immunohistochemistry (IHC) score of 3+ and/or positive by in situ hybridization (ISH)
according to current American Society of Clinical Oncology (ASCO) College of American
Pathologists (CAP) guidelines. Central testing is not required
* Known hormone receptor (HR) status as defined by ASCO/CAP guidelines (based on
pretreatment biopsy material). Hormone receptor positive status can be determined by
either known positive estrogen receptor (ER) or known positive progesterone receptor
(PR) status; hormone receptor negative status must be determined by both known
negative ER and known negative PR
• Patients with clinical stage T1-4, N0-3 disease at presentation and residual invasive
disease postoperatively as defined above are eligible. (Note: Patients with T1a/bN0
tumors are not eligible at initial breast cancer diagnosis are not eligible)
• Patients with residual HR-negative, HER2 positive (+) disease in the breast and/or
lymph nodes per the surgical pathology report are eligible; however, patients with HR+
HER2+ cancers must have node-positive residual disease per the surgical pathology
report in order to qualify for the study. The presence of residual invasive disease in
the breast is not mandatory for these patients
• Patients with weakly ER-positive (1-10%) breast cancer (based on the pretreatment core
biopsy) are eligible even if they have node-negative disease per the surgical
pathology report
• The residual disease tissue (breast and/or lymph nodes) is not required to be
HER2-positive, as eligibility for NCI-2020-03770 (A011801) is based on a positive HER2
status at the time of the initial breast cancer diagnosis
* Note: The presence of micrometastases in lymph nodes after preoperative therapy
counts as residual disease, whereas the presence of isolated tumor cells does not
• Patients with synchronous bilateral invasive disease are eligible provided both
lesions were confirmed to be HER2-positive, and at least one of the lesions meets the
criteria outlined above. Multifocal disease is allowed, as long as the largest
biopsied breast tumor was HER2-positive
• Patients must have received neoadjuvant chemotherapy with one of the following
regimens: docetaxel/trastuzumab/pertuzumab (THP), paclitaxel/methotrexate/cisplatin
(TMP), doxorubicin/cyclophosphamide/paclitaxel/trastuzumab/pertuzumab (AC-TH(P));
docetaxel/carboplatin/trastuzumab/pertuzumab (TCH(P));
fluorouracil/doxorubicin/cyclophosphamide-docetaxel/trastuzumab/pertuzumab
(FAC-TH(P)), or
fluorouracil/epirubicin/cyclophosphamide-docetaxel/trastuzumab/pertuzumab (FEC-TH(P)).
Note: apart from TCHP, where T is docetaxel, treatment with docetaxel or paclitaxel is
acceptable
• Prior receipt of T-DM1 in the neoadjuvant setting is not allowed.
• Prior treatment must have consisted of >= 6 cycles of chemotherapy and
HER2-directed therapy, with a total duration of >= 12 weeks, including at least 9
weeks of preoperative taxane and trastuzumab with or without pertuzumab (or Food
and Drug Administration [FDA]-approved biosimilars). Patients who have received
at least 9 weeks of preoperative taxane, pertuzumab and margetuximab are also
eligible if they received >= 6 cycles of systemic therapy prior to enrollment.
Note: Patients who complete at least nine of a planned twelve doses of weekly
paclitaxel, or three of a planned four doses of docetaxel, but discontinue
prematurely due to toxicity are eligible. Patients receiving dose-dense
chemotherapy regimens are also eligible. Prior use of nab-paclitaxel (Abraxane)
instead of paclitaxel or docetaxel is permitted. Prior use of subcutaneous
trastuzumab (Hylecta) and subcutaneous trastuzumab and pertuzumab (Phesgo) is
also allowed.
• Patients who received neoadjuvant systemic therapy which included experimental
HER2-targeted therapy/therapies are potentially eligible, as long as the
investigational agent was not a HER2-targeted antibody-drug conjugate (e.g.
T-DM1, DS-8201a [trastuzumab deruxtecan]) or a HER2 targeted tyrosine kinase
inhibitor (TKI) (e.g. tucatinib, lapatinib, neratinib).
• Patients may have received =< 1 cycles of T-DM1 in the adjuvant setting. Note: These
patients will be randomized to receive a further 14 cycles of T-DM1 and
tucatinib/placebo as tolerated. The most recent cycle of T-DM1 should have been
administered =< 5 weeks prior to registration
* Note: Both of the following two criteria need to be met for the patient to be
eligible for this study
• An interval of no more than 12 weeks between the completion date of the last
definitive treatment (e.g. postoperative chemotherapy or radiation, or if neither
given, breast surgical date) and the date of registration. Concurrent radiation
therapy is permitted while receiving study treatment
• Patients must be registered on study within =< 180 days of the date of the most
recent definitive breast cancer surgery (not including reconstructive surgery)
• All systemic chemotherapy should have been completed preoperatively unless
participating in EA1181 (CompassHER2 pathologic complete response [pCR]) or the BIG
DECRESCENDO Trial (which is very similar to CompassHER2 pCR in terms of study design,
drugs, and eligibility). However, patients who received 4 cycles of neoadjuvant THP
off study can receive a further 2-4 cycles of chemotherapy postoperatively to meet
eligibility for A011801. Patients who participated in EA1181 or MA41 and proceeded to
surgery immediately after the de-escalated trial regimen must receive postoperative
chemotherapy to complete a total of >= 6 cycles of systemic treatment prior to
enrollment on A011801, as outlined above (e.g. 4 cycles pre-operatively, and 2 cycles
post-operatively). The postoperative chemotherapy regimen prescribed is at the
discretion of the treating oncologist (i.e. 2-4 cycles AC or THP, other). Continuation
of trastuzumab + pertuzumab (HP) pre- or post-operatively as maintenance therapy
(while awaiting a surgical date or an official pathology report) is allowed for all
study participants
• Toxicities related to prior systemic treatment should have resolved or be at baseline,
apart from alopecia and peripheral neuropathy =< grade 1
• Adequate excision: surgical removal of all clinically evident disease in the breast
and lymph nodes as follows:
• Breast surgery: total mastectomy with no gross residual disease at the margin of
resection, or breast-conserving surgery with histologically negative margins of
excision
• For patients who undergo breast-conserving surgery, the margins of the resected
specimen must be histologically free of invasive tumor and ductal carcinoma in
situ (DCIS) as determined by the local pathologist. If pathologic examination
demonstrates tumor at the line of resection, additional operative procedures may
be performed to obtain clear margins. If tumor is still present at the resected
margin after re-excision(s), the patient must undergo total mastectomy to be
eligible. Patients with margins positive for classic lobular carcinoma in situ
(LCIS) are eligible without additional resection
• Lymph node surgery ** The axilla needs to be evaluated with either sentinel node
biopsy or axillary lymph node dissection. If patients have a sentinel lymph node
biopsy and sentinel nodes are negative, no further axillary treatment is
necessary. If patients have isolated tumor cells (ITCs) in the setting of
residual breast disease, at least one of the following is required: axillary
lymph node dissection (ALND) or planned nodal irradiation. If patients have
micro- or macro-metastatic nodal disease, ALND and planned nodal irradiation are
required. Of note, co-enrollment on Alliance A011202 is not allowed
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Absolute neutrophil count (ANC) >= 1,000/mm^3
• Hemoglobin >= 8 g/dL (Note: packed red blood cells [PRBC] transfusion is not permitted
to achieve eligibility)
• Platelet count >= 100,000/mm^3
• Creatinine =< 1.5 x upper limit of normal (ULN)
• Total bilirubin =< 1.0 x upper limit of normal (ULN) or direct bilirubin within the
institutional normal range for patients with Gilbert's syndrome
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit
of normal (ULN)
• Screening left ventricular ejection fraction (LVEF) >= 50% on echocardiogram (ECHO) or
multiple-gated acquisition (MUGA) after receiving neoadjuvant chemotherapy and no
decrease in LVEF by more than 15% absolute percentage points from the pre-chemotherapy
LVEF. Or, if pre-chemotherapy LVEF was not assessed, the screening LVEF must be >= 55%
after completion of neoadjuvant chemotherapy. Note: LVEF assessment may be repeated
once up to 3 weeks following the initial screening assessment to assess eligibility
Exclusion Criteria:
• No adjuvant treatment with any anti-cancer investigational drug within 28 days prior
to registration
• Not pregnant and not nursing, because this study involves an agent that has known
genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing
potential only, a negative serum pregnancy test done =< 7 days prior to registration
is required
• Patients with known active and/or untreated hepatitis B or hepatitis C or chronic
liver disease are ineligible. Patients with a diagnosis of hepatitis B or C that has
been treated and cleared and normal liver function are eligible to participate in the
study if the other eligibility parameters are met
• Stage IV (metastatic) breast cancer
• History of any prior (ipsi- or contralateral) invasive breast cancer within 3 years of
registration
• Patients with ER+ HER2+ residual invasive disease that is lymph node-negative per the
surgical pathology report
• Evidence of recurrent disease following preoperative therapy and surgery
• Patients for whom radiotherapy would be recommended for breast cancer treatment but
for whom it is contraindicated because of medical reasons (e.g., connective tissue
disorder or prior ipsilateral breast radiation)
• History of exposure to the following cumulative doses of anthracyclines: doxorubicin >
240 mg/m^2; epirubicin or liposomal doxorubicin-hydrochloride (Myocet) > 480 mg/m^2.
For other anthracyclines, exposure equivalent to doxorubicin > 240 mg/m^2
• Cardiopulmonary dysfunction as defined by any of the following:
• History of National Cancer Institute (NCI) CTCAE version (v) 5.0 grade >= 3
symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA)
criteria class >= II
• Angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia not
controlled by adequate medication, severe conduction abnormality, or clinically
significant valvular disease
• High-risk uncontrolled arrhythmias: i.e., atrial tachycardia with a heart rate >
100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or
higher-grade atrioventricular block (AV)-block (second degree AV-block type 2
[Mobitz 2] or third degree AV-block)
• Significant symptoms (grade >= 2) relating to left ventricular dysfunction,
cardiac arrhythmia, or cardiac ischemia while or since receiving preoperative
therapy
• History of a decrease in left ventricular ejection fraction (LVEF) to < 40% with
prior trastuzumab treatment (e.g., during preoperative therapy)
• Uncontrolled hypertension (systolic blood pressure > 180 mmHg and/or diastolic
blood pressure > 100 mmHg)
• Current severe, uncontrolled systemic disease
• Major surgical procedure unrelated to breast cancer or significant traumatic injury
within 28 days prior to registration or anticipation of the need for major surgery
during the course of study treatment
• History of intolerance, including grade 3 to 4 infusion reaction or hypersensitivity
to trastuzumab or murine proteins or any components of the product
• Peripheral neuropathy of any etiology that exceeds grade 1
• Assessment by the investigator as being unable or unwilling to comply with the
requirements of the protocol
• Use of a strong CYP3A4 or CYP2C8 inhibitor within 2 weeks, or use of a strong CYP3A4
or CYP2C8 inducer within 5 days prior to registration is prohibited.
• Please note that use of sensitive CYP3A substrates should be avoided two weeks
before registration and during study treatment. Additionally, CYP3A4 or CYP2C8
inducers are prohibited as concomitant medications within 5 days following
discontinuation of tucatinib treatment. Patients who require medications that are
known to be sensitive substrates of CYP3A4 with a narrow therapeutic window
should be excluded.
Invasive Breast Carcinoma, HER2 Positive Breast Carcinoma, Multifocal Breast Carcinoma, Synchronous Bilateral Breast Carcinoma, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8, Anatomic Stage IIB Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Prognostic Stage II Breast Cancer AJCC v8, Prognostic Stage IIA Breast Cancer AJCC v8, Prognostic Stage IIB Breast Cancer AJCC v8, Prognostic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IA Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IIIB Breast Cancer AJCC v8, Anatomic Stage IIIC Breast Cancer AJCC v8, Prognostic Stage I Breast Cancer AJCC v8, Prognostic Stage IA Breast Cancer AJCC v8, Prognostic Stage IB Breast Cancer AJCC v8, Prognostic Stage III Breast Cancer AJCC v8, Prognostic Stage IIIB Breast Cancer AJCC v8, Prognostic Stage IIIC Breast Cancer AJCC v8
UT Southwestern; Parkland Health & Hospital System
Monitoring Neoadjuvant Chemotherapy of Breast Cancer Using 3D Subharmonic Aided Pressure Estimation
This phase II/III trial studies if contrast-enhanced ultrasound (CEUS) using a contrast
agent, perflutren lipid microspheres (Definity), can predict the early response of breast
cancer to neoadjuvant chemotherapy by estimating the pressure gradient between the breast
cancer and surrounding tissues. To estimate the pressures noninvasively, subharmonic (half of
fundamental frequency) aided pressure estimation (SHAPE) using CEUS will be utilized. The
study hypothesis is that the subharmonic signal difference in the tumor relative to the
normal tissue can predict breast cancer NAC response after 10% of therapy regimen.
• Provide signed and dated informed consent form
• Willing to comply with all study procedures and be available for the duration of the
study
• At least 21 years old
• Be diagnosed with breast cancer (T1 or greater LABC, any N and M0)
• Be scheduled for neoadjuvant chemotherapy
• Be medically stable
• Be conscious and able to comply with study procedures
• If a female of child-bearing potential, must have a negative urine pregnancy test
Exclusion Criteria:
• Females who are pregnant or nursing
• Patients with other primary cancers requiring systemic treatment
• Patients with any distal metastatic disease
• Patients undergoing neoadjuvant endocrine therapy
• Patients who are medically unstable, patients who are seriously or terminally ill, and
patients whose clinical course is unpredictable. For example:
• Patients on life support or in a critical care unit;
• Patients with unstable occlusive disease (e.g., crescendo angina);
• Patients with clinically unstable cardiac arrhythmias, such as recurrent
ventricular tachycardia;
• Patients with uncontrolled congestive heart failure (New York Heart Association
[NYHA] Class IV);
• Patients with recent cerebral hemorrhage;
• Patients who have undergone surgery within 24 hours prior to the study
sonographic examination
• Patients with known hypersensitivity or allergy to any component of Definity
• Patients with unstable cardiopulmonary conditions or respiratory distress syndrome
• Patients with uncontrollable emphysema, pulmonary vasculitis, pulmonary hypertension
or a history of pulmonary emboli
Locally Advanced Breast Carcinoma, Anatomic Stage IIIA Breast Cancer AJCC v8, Prognostic Stage IIIA Breast Cancer AJCC v8, Breast - Female, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IIIB Breast Cancer AJCC v8, Anatomic Stage IIIC Breast Cancer AJCC v8, Prognostic Stage III Breast Cancer AJCC v8, Prognostic Stage IIIB Breast Cancer AJCC v8, Prognostic Stage IIIC Breast Cancer AJCC v8
UT Southwestern; Parkland Health & Hospital System
A Study of HMBD-002, a Monoclonal Antibody Targeting VISTA, as Monotherapy and Combined With Pembrolizumab
This is a phase 1/2, open-label, multi-center, first-in-human, two-stage (Part 1: dose
escalation and Part 2: dose expansion) study evaluating multiple doses and schedules of
intravenously (IV) administered HMBD-002, with or without pembrolizumab, in patients with
advanced solid tumors (i.e., locally advanced and unresectable, or metastatic).
Inclusion Criteria (Phase 1 and 2 Stages)
1. Histologic or cytologic evidence of a malignant solid cancer (any histology) with
advanced or metastatic disease and no available therapies known to confer clinical
benefit.
2. Tumor tissue, or paraffin block, ideally from the patient's most recent biopsy. A
fresh tumor biopsy will be obtained if archival samples are not available.
3. Measurable by Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
4. At least 18 years old.
5. An Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
6. Adequate hematopoietic, kidney, and liver functions.
7. A left ventricular ejection fraction (LVEF) ≥ 45%.
8. Women of childbearing potential (WOCBP) must not be pregnant or breastfeeding. A WOCBP
must agree to follow contraceptive guidance during the treatment period and for at
least 120 days after the last dose of study treatment.
9. Male subjects must agree to follow contraceptive guidance during the study period and
for at least 120 days after the last dose of study treatment.
10. Patient must give informed written consent for the study.
Inclusion Criteria for HMBD-002 Phase 2 Stage
Triple Negative Breast Cancer (TNBC)
1. Histologic or cytologic evidence of TNBC that is advanced or metastatic.
2. Will be requested to undergo a tumor biopsy before treatment and after 6 weeks of
treatment.
3. Must have received appropriate treatment with at least one prior regimen for TNBC and
there are no available therapies known to confer clinical benefit.
Non-Small Cell Lung Cancer (Monotherapy and Combination)
1. Histologic or cytologic evidence of NSCLC that is advanced or metastatic.
2. Will be requested to undergo a tumor biopsy before treatment and after 6 weeks of
treatment.
3. Absence of an activating mutation of the EGFR or ALK.
4. Must have received treatment with an approved therapy if there are other genomic
aberrations for which targeted therapies are approved and available.
5. Must have had disease progression on at least one approved or comparable standard
therapy for NSCLC.
6. Must have received appropriate prior treatment with a mAb to PD-1 or PD-L1.
Multiple Other Cancers (Combination Therapy Baskets)
1. Histologic or cytologic evidence of an advanced or metastatic cancer aside from TNBC
and NSCLC with no available therapies known to confer clinical benefit.
2. Will be requested to undergo a tumor biopsy before treatment and after 6 weeks of
treatment.
3. Must have had appropriate treatment for their specific cancer and there is an absence
of available therapy with a reasonable likelihood of conferring clinical benefit.
Exclusion Criteria
1. If the patient received prior therapy with an anti-PD-1 or anti-PD-L1 mAb or with an
agent targeting stimulatory or co-inhibitory T-cell receptor and was discontinued from
that treatment due to a Grade 3 or higher immune related adverse event.
2. Received radiotherapy within 2 weeks of treatment.
3. Received radiotherapy exceeding 30 Gray (Gy) to the lung within 6 months of the first
dose of study medication.
4. Received an allogeneic tissue/solid organ transplant.
5. Received a live or live-attenuated vaccine within 30 days prior to the first dose of
study medication.
6. Received a VISTA targeting agent.
7. The patient must have recovered from all AEs due to previous therapies to ≤Grade 1 or
baseline.
8. The patient has an active autoimmune disease that required systemic treatment in the
past.
9. Presence of an uncontrolled endocrine disorder.
10. Presence of clinically significant cardiovascular disease.
11. History of (non-infectious) pneumonitis or interstitial pulmonary disease that
required steroids or has current pneumonitis or interstitial pulmonary disease.
12. Presence of uncontrolled, clinically significant pulmonary disease.
13. A previous a severe hypersensitivity reaction (≥ Grade 3) to pembrolizumab and/or any
of its excipients.
14. A diagnosis of immunodeficiency or is receiving chronic systemic corticosteroids at a
dose that exceeds 10 mg daily of prednisone equivalent or any other form of
immunosuppressive therapy within 7 days prior the first dose of study drug. Inhaled or
topical steroids are permitted in the absence of active autoimmune disease.
15. An uncontrolled intercurrent illness that would limit compliance with the study.
16. A positive status for human immunodeficiency virus (HIV).
17. A known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C
viral (defined as HCV RNA detected) infection.
18. Oxygen-dependence.
19. A medical condition which, in the opinion of the Investigator, places the patient at
an unacceptably high risk for toxicity.
20. A positive COVID test within one week of study treatment if not fully vaccinated.
21. Another active malignancy that is progressing or has required active treatment within
the past 3 years.
22. Known active central nervous system metastases and/or carcinomatous meningitis.
Drug: HMBD-002, Drug: Pembrolizumab
Cancer, Metastatic Cancer, Triple Negative Breast Cancer, Advanced Solid Tumor, Nonsmall Cell Lung Cancer, Malignant Neoplasm, Breast - Female, Breast - Male, Lung/Thoracic, Melanoma, skin, Other Skin, Tumor, Solid
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 Study of Oral LOXO-292 (Selpercatinib) in Pediatric Participants With Advanced Solid or Primary Central Nervous System (CNS) Tumors (LIBRETTO-121)
This is an open-label, multi-center Phase 1/2 study of oral LOXO-292 in pediatric
participants with an activating rearranged during transfection (RET) alteration and an
advanced solid or primary CNS tumor.
• Advanced or metastatic solid or primary CNS tumor which has failed standard of care
therapies
• Evidence of an activating RET gene alteration in the tumor and/or blood
• Measurable or non-measurable disease
• Karnofsky (participants 16 years and older) or Lansky (participants younger than 16)
performance score of at least 50
• Participant with primary CNS tumors or cerebral metastases must be neurologically
stable for 7 days prior and must not have required increasing doses of steroids within
the last 7 days
• Adequate hematologic, hepatic and renal function.
• Ability to receive study drug therapy orally or via gastric access
• Willingness of men and women of reproductive potential to observe conventional and
effective birth control
Exclusion Criteria:
• Major surgery within two weeks prior to planned start of LOXO-292
• Clinically significant, uncontrolled cardiac, cardiovascular disease or history of
myocardial infarction within 6 months prior to planned start of LOXO-292
• Active uncontrolled systemic bacterial, viral, fungal or parasitic infection
• Clinically significant active malabsorption syndrome
• Pregnancy or lactation
• Uncontrolled symptomatic hyperthyroidism or hypothyroidism (i.e. the participant
required a modification to current thyroid medication in the 7 days before start of
LOXO-292)
• Uncontrolled symptomatic hypercalcemia or hypocalcemia
• Known hypersensitivity to any of the components of the investigational agent, LOXO-292
or Ora-Sweet® SF and OraPlus®, for participants who will receive LOXO-292 suspension
• Prior treatment with a selective RET inhibitor(s) (including investigational selective
RET inhibitor[s])
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
A Study of Intravesical Enfortumab Vedotin For Treatment of Patients With Non-muscle Invasive Bladder Cancer (NMIBC)
This study will test a drug called enfortumab vedotin in participants with a type of bladder
cancer called non-muscle invasive bladder cancer (NMIBC).
This study will also evaluate what the side effects are and if the drug works to treat NMIBC.
A side effect is anything a drug does to your body besides treating your disease.
In this study enfortumab vedotin will be put into the bladder using a catheter. A catheter is
a thin tube that can be put into your bladder.
• Histologically confirmed, non-muscle invasive urothelial carcinoma with carcinoma in
situ (CIS) (with or without papillary disease)
• Predominant histologic component (>50 percent) must be urothelial (transitional cell)
carcinoma
• Participants must have high-risk Bacillus Calmette-Guerin (BCG) •unresponsive
disease, defined as (where adequate BCG therapy is defined as one of the following: 5
of 6 doses of an initial induction course + at least 2 of 3 doses maintenance therapy
or 5 of 6 doses of an initial induction course + at least 2 of 6 doses of a second
induction course):
• Persistent or recurrent CIS alone or with recurrent Ta/T1 (noninvasive papillary
disease/tumor invades the subepithelial connective tissue) disease within 12
months of completion of adequate BCG therapy.
• Recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG
therapy, or
• T1 high-grade disease at the first evaluation following an induction BCG course
(at least 5 or 6 doses)
• Participant must be ineligible for or refusing a radical cystectomy
• All visible papillary Ta/T1 tumors must be completely resected within 60 days prior to
enrollment.
• Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2.
Exclusion Criteria:
• Current or prior history of muscle-invasive urothelial carcinoma or metastatic
disease.
• Nodal or metastatic disease as noted on computed tomography (CT) or magnetic resonance
imaging (MRI) within 3 months prior to study treatment
• Concomitant upper tract urothelial carcinoma as noted on CT or MRI urogram performed
within 3 months prior to study treatment
• Prior or concomitant urothelial carcinoma of the prostatic urethra within 6 months
prior to study treatment
• Participants with tumor-related hydronephrosis
• Participant has received other systemic anticancer therapy including chemotherapy,
biologic therapy, immunotherapy, targeted therapy, endocrine therapy, and/or
investigational agent within 4 weeks or intravesical therapy within 6 weeks of first
dose of study treatment
• Participant has had any prior radiation to the bladder for urothelial cancer
Safety and Efficacy Study of IMSA101 in Refractory Malignancies
Open-label, dose escalation (Phase I) and dose expansion (Phase IIA) study of patients
receiving intra-tumoral IMSA101 alone or in combination with an immune checkpoint inhibitor
(ICI) (Phase I and II)
1. Signed informed consent and mental capability to understand the informed consent
2. Male or female patients > 18 years of age
3. Histologically or cytologically documented locally advanced or metastatic solid tumor
malignancies refractory to or otherwise ineligible for treatment with standard-of-care
agents/regimens, including but not limited to:
• Malignant melanoma
• Hormone receptor negative breast cancer
• Gastro-esophageal cancer
• Non-small cell lung cancer
• Head and neck cancer
• Hepatoma
• Renal cell carcinoma
4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
5. Evaluable or measurable disease as follows:
• A minimum of 3 RECIST-evaluable lesions: one that is suitable for injection and
biopsied; one non-injected that will be biopsied for abscopal effect; and one
measurable lesion that will be followed for response only.
• Injectable tumors shall be accessed by intralesional (cutaneous) or percutaneous
injection only, including those lesions that are visible, palpable, or detectable
by standard radiographic or ultrasound methods. Neither surgical procedures nor
endoscopically-guided injections including those to endobronchial, endoluminal,
or endosinusial spaces shall be allowed. While no anatomic locations are required
or disallowed, lesions selected for intratumoral injection must, in the opinion
of the investigator:
• Not be immediately adjacent to blood vasculature or other physiologic landmarks
in such a way that will accrue undue safety risk to the patient
• Have longest diameter ≥ 10 mm and ≤ 50 mm
• Be fully efficacy evaluable per RECIST v1.1 criteria
6. Life expectancy > 3 months (Phase I) and > 6 months (Phase IIA)
7. ECG without evidence of clinically meaningful conduction abnormalities or active
ischemia as determined by the investigator
8. Acceptable organ and marrow function as defined below:
• Absolute neutrophil count > 1,500 cells/μL
• Platelets > 50,000 cells/μL
• Total bilirubin ≤ 1.5 times the upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine transaminase (ALT) ≤ 2.5 times ULN. If
liver metastases are present, AST/ALT < 5 times ULN
• Serum creatinine < 1.5 mg/dL and a measured creatinine clearance ≥ 50 mL/min
using the Cockcroft-Gault formula
• Prothrombin time (PT)/partial thromboplastin time (PTT) ≤ 1.5 times ULN
9. Women of child-bearing potential (defined as a female who has experienced menarche and
who has not undergone successful surgical sterilization (hysterectomy, bilateral
salpingectomy, or bilateral oophorectomy) or is not postmenopausal (defined as
amenorrhea for at least 12 consecutive months with an appropriate clinical profile at
the appropriate age, e.g., greater than 45 years) must have a negative serum pregnancy
test prior to first dose of study drug
10. Male and female patients with reproductive potential must agree to use two forms of
highly effective contraception throughout the study
11. Phase I combination only: Demonstrated RECIST stable disease through ≥ 4 consecutive
cycles of an approved PD-1 or PD-L1 targeted ICI with no Grade ≥ 3 CTCAE events
considered by the investigator to be drug-related.
Exclusion Criteria:
1. Anti-cancer therapy within 4 weeks or < 5 half-lives of the first dose of study drug.
2. Failure to recover to Grade 1 or less from clinically significant AEs due to prior
anti-cancer therapy.
3. Known untreated brain metastases or treated brain metastases that have not been stable
(scan showing no worsening of central nervous system (CNS) lesion[s] and no
requirement of corticosteroids) ≥ 4 weeks prior to study enrollment
4. Baseline prolongation of QT/QTc interval (QTc interval > 470)
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 opinion of the
investigator would limit compliance with study requirements
6. Women who are pregnant or breastfeeding
7. Phase I combination only: Prior tumor progression through PD-1 or PD-L1 targeted ICI
therapy.
A Study of ZN-c3 in Participants With Solid Tumors
This is a Phase 1/2 open-label, multicenter study, evaluating the safety, tolerability,
efficacy, pharmacokinetics (PK) and pharmacodynamics of ZN-c3 alone and in combination with
other drugs.
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, Corpus Uteri, Peritoneal Cancer
• Histologically or cytologically documented locally advanced or metastatic solid tumor
malignancy.
• Progressed or was intolerant to all available therapies known to confer clinical
benefit appropriate for their tumor type, and for which the patient was eligible and
willing to receive, or refused SOC treatments that are perceived to have marginal
clinical benefit.
• Adequate bone marrow, kidney and liver function.
• Performance status of 0 or 1.
• Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade 1
except for AEs not constituting a safety risk by Investigator judgement.
Exclusion Criteria:
• Prior treatment targeting ILT2 and/or ILT4 or targeting HLA-G.
Drug: NGM707, Drug: NGM707 plus pembrolizumab, Drug: NGM707, Drug: NGM707, Drug: NGM707, Drug: NGM707 plus pembrolizumab, Drug: NGM707 plus pembrolizumab
Esophageal Cancer, Breast Cancer, Melanoma, Gastric Cancer, Colorectal Cancer, Ovarian Cancer, Glioblastoma, Cervical Cancer, Renal Cell Carcinoma, Non Small Cell Lung Cancer, Mesothelioma, Cholangiocarcinoma, Pancreatic Ductal Adenocarcinoma, Brain and Nervous System, Breast - Female, Breast - Male, Kidney, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Skin, Ovary, Pancreas, Squamous Cell Carcinoma of Head and Neck, Endocervical Cancer
Web-Based Physical Activity Intervention in Improving Long Term Health in Children and Adolescents With Cancer
This randomized clinical phase III trial studies how well web-based physical activity
intervention works in improving long term health in children and adolescents with cancer.
Regular physical activity after receiving treatment for cancer may help to maintain a healthy
weight and improve energy levels and overall health.
• All cancer cases with an International Classification of Diseases for Oncology (ICD)-O
histologic behavior code of two "2" (carcinoma in situ) or three "3" (malignant), in
remission
• Patient must have completed curative therapy (surgery and/or radiation and/or
chemotherapy) within the past 12 months at a Childrens Oncology Group (COG)
institution
• Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1, or 2; use Lansky for patients =< 16 years of age
• At the time of consent, patient or parent/guardian reports less than 420 minutes of
moderate to vigorous physical activity over the last week
• Patient and at least one parent/guardian are able to read and write English, Spanish,
and/or French; at least 1 parent/guardian must be able to read and write English,
Spanish, and/or French in order to assist the patient with using their physical
activity tracking device account
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Exclusion Criteria:
• Patients with previous hematopoietic stem cell transplant (HSCT)
• Patients with significant concurrent disease, illness, psychiatric disorder or social
issue that would compromise patient safety or compliance with protocol therapy, or
interfere with consent, study participation, follow up, or interpretation of study
results
• Female patients who are pregnant are not eligible; women of childbearing potential
require a negative pregnancy test
• Female patient who is postmenarcheal and has not agreed to use an effective
contraceptive method (including abstinence) for the duration of study participation
• Patients with a cognitive, motor, visual or auditory impairment that prevents computer
use (e.g. unresolved posterior fossa syndrome) are not eligible
Study of TT-00420 Tablet as Monotherapy and Combination Therapy in Patients With Advanced Solid Tumors
This is a Phase Ib/II, multicenter, open-label study to evaluate the safety and preliminary
efficacy of TT-00420 tablet, as monotherapy or in combination regimens, in patients with
advanced solid tumors.
1. ≥ 18 years of age
2. Histopathological or cytologically documented locally advanced or metastatic solid
tumors who have no available standard therapeutic treatment options
3. At least one measurable lesion as defined by RECIST V1.1 criteria for solid tumors
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
5. Adequate organ function confirmed at screening and within 10 days of initiating
treatment, as evidenced by:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
• Hemoglobin (Hgb) ≥ 8 g/dl
• Platelets (plt) ≥ 75 x 10^9/L
• AST/SGOT and ALT/SGPT ≤ 2.5 x Upper Limit of Normal (ULN) or ≤ 5.0 x ULN if liver
metastases are present
• Total bilirubin ≤ 1.5 x ULN
• Calculated creatinine clearance ≥ 50 mL/min (Cockcroft Gault formula)
6. Negative pregnancy test within 72 hours before starting study treatment in all
premenopausal women and women < 12 months after the onset of menopause
7. Must agree to take sufficient contraceptive methods to avoid pregnancy during the
study and until at least 6 months after ceasing study treatment
8. Able to sign informed consent and comply with the protocol
Exclusion Criteria:
1. Women who are pregnant or lactating
2. Women of child-bearing potential (WOCBP) who do not use adequate birth control
3. Patients with any hematologic malignancy, including leukemia (any form), lymphoma, and
multiple myeloma
4. Patients with a history of primary central nervous system tumors or carcinomatous
meningitis.
5. Patients with the following mood disorders as judged by the Investigator or a
psychiatrist:
• Medically documented history of or active major depressive episode, bipolar
disorder (I or II), obsessive-compulsive disorder, schizophrenia; a history of
suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm
to others)
• ≥ CTCAE grade 3 anxiety
6. Impaired cardiac function or significant diseases, including but not limited to any of
the following:
• left ventricular ejection fraction (LVEF) < 45% as determined by multigated
acquisition (MUGA) scan or echocardiogram (ECHO)
• Congenital long QT syndrome
• QTcF ≥ 480 msec on screening ECG
• Unstable angina pectoris ≤ 3 months prior to starting study drug
• Acute myocardial infarction ≤ 3 months prior to starting study drug
7. Patients with:
• unresolved diarrhea ≥ CTCAE grade 2, or
• impairment of gastrointestinal (GI) function, or
• GI disease that may significantly alter the absorption of TT-00420
8. Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g.,
uncontrolled hypertension, uncontrolled hypertriglyceridemia, or active or
uncontrolled infection) that could cause unacceptable safety risks or compromise
compliance with the protocol
9. Patients who have received chemotherapy, targeted therapy, or immunotherapy ≤ 4 weeks
(6 weeks for nitrosourea or mitomycin-C) prior to starting study drug or who have not
recovered from side effects of such therapy
10. Patients who have received wide field radiotherapy ≤ 4 weeks or limited field
radiation for palliation ≤ 2 weeks prior to starting study drug or who have not
recovered from side effects of such therapy
11. Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or
who have not recovered from side effects of such therapy
12. Patients who have been treated with any hematopoietic colony-stimulating growth
factors (e.g., G-CSF, GM-CSF) ≤ 4 weeks prior to starting study drug.
13. Patients who are currently receiving treatment with therapeutic doses of warfarin
sodium or any other coumarin-derivative anticoagulants
14. Patients who have received systemic corticosteroids ≤ 2 weeks prior to starting study
drug or who have not recovered from the side effects of such treatment.
15. Patients who are currently receiving treatment with strong CYP3A inhibitors or
inducers ≤ 2 weeks prior to starting study drug.
16. Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not
mandatory; patients with well controlled HIV might be enrolled)
17. Known history of active infection with Hepatitis B or Hepatitis C
18. Has received a live-virus vaccination within 30 days of planned first dose
19. Inability to swallow or tolerate oral medication
20. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that, in the opinion of the investigator, might confound the results of the trial,
interfere with the patient's safe participation and compliance in the trial.
Prostate Cancer, Sarcoma, Gastric Cancer, Bladder Cancer, Cholangiocarcinoma, Gallbladder Cancer, Thyroid Cancer, Triple Negative Breast Cancer, HER2-negative Breast Cancer, Advanced Solid Tumor, Breast - Female, Breast - Male, Lung/Thoracic, Other Digestive Organ, Other Skin, Other Urinary, Prostate, Stomach, Thyroid, Small Intestine, Small-cell Lung Cancer
Niraparib in the Treatment of Patients With Advanced PALB2 Mutated Tumors (PAVO)
The purpose of this study is to further evaluate the efficacy and safety of niraparib in
patients with locally advanced or metastatic solid tumors and a pathogenic or likely
pathogenic tumor PALB2 (tPALB2) mutation.
• Participants must be at least 18 years of age or older.
• Participants must have a histologically or cytologically confirmed diagnosis of
locally advanced or metastatic solid tumor(s).
• Participants must have tested positive for a pathogenic or likely pathogenic tPALB2
gene mutation using a CLIA-certified laboratory as described in the Next-Generation
Sequencing (NGS) Laboratory Manual.
• Participants who have stable and asymptomatic Central Nervous System (CNS) disease
must be receiving a stable (for at least 7 days) or decreasing corticosteroid dose at
the time of study entry.
• Participants must submit fresh or archived (collected within 24 months of enrollment)
Formalin-Fixed Paraffin-Embedded (FFPE) tumor sample to the central laboratory for
post-enrollment confirmation of tPALB2 status.
• Participants must have received all standard therapies appropriate for their tumor
type and stage of disease or, in the opinion of the Investigator, the patient would be
unlikely to tolerate or derive clinically meaningful benefit from appropriate standard
of care therapy, or the participant has no satisfactory alternative treatments.
Exclusion Criteria:
• Participants have other active concomitant malignancy that warrants systemic,
biologic, or hormonal therapy.
• Participants who have ovarian or prostate cancer.
• Participants who have variants of undetermined significance (VUS), but not pathogenic
variants of PALB2, at the time of screening.
• Participants who relapsed while receiving platinum based therapy in the
adjuvant/curative setting.
• Participants progressing within 14-18 weeks while receiving platinum based therapy in
the metastatic setting.
• Participants who have received Poly (ADP-ribose) polymerase (PARP) inhibitor(s) in
prior lines of treatment.
• Participants with leptomeningeal disease, carcinomatous meningitis, symptomatic brain
metastases, or radiologic signs of CNS hemorrhage.
• Participants with germline or somatic BRCA1 or BRCA2 mutations.
• Participant has systolic blood pressure (BP) over 140 mmHg or diastolic BP over 90
mmHg, despite optimal medical therapy.
• Participants have previously or are currently participating in a treatment study of an
investigational agent within 3 weeks of the first dose of therapy preceding the study.
• Participants have received prior systemic cytotoxic chemotherapy, biological therapy,
or hormonal therapy for cancer, or received radiation therapy within 3 weeks of the
first dose therapy preceding the study.
Drug: Niraparib
Endometrial Cancer, Esophageal Cancer, Melanoma, Pancreatic Cancer, Metastatic Cancer, Head and Neck Cancer, Solid Tumor, Breast - Female, Colon, Corpus Uteri, Esophagus, Lung/Thoracic, Melanoma, skin, Other Urinary, Pancreas, Breast Tumor, Colon Tumor, Malignant, Lung Tumor, Urologic Cancer, Locally Advanced Solid Tumor
PALB2, Solid Tumor, Metastatic Solid Tumor, Locally Advanced Solid Tumor, Advanced Solid Tumor, Local Solid Tumor, PALB2 Mutation, Niraparib, tPALB2, tPALB2 Mutation, Pathogenic tumor, Lung Tumor, Breast Tumor, Colon Tumor, Zejula, Pancreatic Cancer, Urologic Cancer, Melanoma, Metastatic Cancer, Head and Neck Cancer, Endometrial Cancer, Esophageal Cancer
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
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 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
Stereotactic Radiosurgery (SRS) Dose-Escalation Study for Brain Metastasis (SRS)
SRS dose escalation for brain metastases in radiation-naïve patients will establish true
tolerable doses, which may exceed the current standard doses. This may lead to an improvement
in local control, patient survival, and/or quality-of life.
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