| Eligibility |
Inclusion Criteria:
- Documented informed consent of the participant and/or legally authorized
representative
- Assent, when appropriate, will be obtained per institutional guidelines
- Agreement to allow the use of archival tissue from biopsy or tissue block cytology
obtained at time of last disease recurrence. If biopsy is not possible or patient
refuses, the principal investigator (PI) may allow an earlier biopsy to be tested. If
unavailable, exceptions may be granted with Study PI approval
- Age: >= 18 years
- Eastern cooperative oncology group (ECOG) =< 2
- Histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal
cancer. May not have non epithelial tumors or ovarian tumors with low malignant
potential (ie, borderline tumors) or mucinous tumors or small cell carcinoma tumors or
low grade serous carcinoma
- Recurrent, platinum resistant disease (defined as progression within <6 months from
completion of platinum-based therapy. The date should be calculated from the last
administered dose of platinum therapy)
- Measurable disease per response evaluation criteria in solid tumors (RECIST) 1.1 or
evaluable disease (defined as solid and/or cystic abnormalities on radiographic
imaging that do not meet RECIST 1.1 definitions for target lesions OR ascites and/or
pleural effusion that has been pathologically demonstrated to be disease related in
the setting of CA125 >2x upper limit of normal [ULN])
- No more than 4 prior cytotoxic regimens (including primary therapy). Hormonal
therapies (tamoxifen, aromatase inhibitors) or other prior poly (ADP-Ribose)
polymerase (PARP) inhibitors will not count toward the prior regimen limit. Prior PARP
inhibotor therapy is allowed
- Fully recovered from the acute toxic effects (except alopecia) to =< Grade 1 to prior
anti-cancer therapy
- MyChoice HRD test should show BRCA wt and no HRD. No deleterious germline BRCA 1/2
mutations are allowed
- Absolute neutrophil count (ANC) >= 1,500/mm^3 (performed within 14 days prior to day 1
of protocol therapy unless otherwise stated)
- Platelets >= 150,000/mm^3 (performed within 14 days prior to day 1 of protocol therapy
unless otherwise stated)
- Total bilirubin =< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease,
when =< 2.0 X ULN is acceptable (performed within 14 days prior to day 1 of protocol
therapy unless otherwise stated)
- Aspartate aminotransferase (AST) =< 2.5 x ULN, unless liver metastases are present, in
which case =< 5 x ULN (performed within 14 days prior to day 1 of protocol therapy
unless otherwise stated)
- Alanine aminotransferase (ALT) =< 2.5 x ULN, unless liver metastases are present, in
which case =< 5 x ULN (performed within 14 days prior to day 1 of protocol therapy
unless otherwise stated)
- Serum Creatinine =< 1.5 x ULN or creatine clearance of >= 60 mL/min per 24 hour urine
test or the Cockcroft-Gault formula (performed within 14 days prior to day 1 of
protocol therapy unless otherwise stated)
- Prothrombin (PT) =< 1.25 x ULN (performed within 14 days prior to day 1 of protocol
therapy unless otherwise stated)
- Hemoglobin >= 9 g/dL (performed within 14 days prior to day 1 of protocol therapy
unless otherwise stated)
- Women of childbearing potential (WOCBP): negative highly sensitive urine or serum
pregnancy test (highly sensitive urine test will be required if serum pregnancy test
is not available) (performed within 14 days prior to day 1 of protocol therapy unless
otherwise stated)
- Normal blood pressure or adequately controlled hypertension (performed within 14 days
prior to day 1 of protocol therapy unless otherwise stated)
- Agreement by subjects of childbearing potential* to use a highly effective method of
birth control or abstain from heterosexual activity for the course of the study
through at least 180 days after the last dose of protocol therapy
- Childbearing potential defined as not being surgically sterilized (men and women)
or have not been free from menses for > 1 year (women only)
Exclusion Criteria:
- Chemotherapy, biological therapy, immunotherapy within 21 days prior to Day 1 of
protocol
- Radiation therapy encompassing > 20% of the bone marrow within 2 weeks. Any radiation
therapy within 1 week prior to Day 1 therapy
- Colony-stimulating factors (e.g. granulocyte colony-stimulating factor, granulocyte
macrophage colony stimulating factor, or recombinant erythropoietin within 4 weeks
prior to day 1
- Receipt of a transfusion (platelets or red blood cells) within 4 weeks of D1
- Known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy
that persisted > 4 weeks and was related to the most recent treatment
- Diagnosis, detection, or treatment of another type of cancer = 2 years prior to
initiating protocol therapy (except basal or squamous cell carcinoma of the skin and
cervical cancer in situ that has been definitively treated
- Strong CYP3A4 inducers/ inhibitors within 14 days prior to Day 1 of protocol therapy
- UGT1A1 inhibitors within 14 days prior to Day 1 of protocol therapy
- Herbal medications containing selenium within 14 days prior to Day 1 of protocol
therapy
- Vitamin E within 14 days prior to Day 1 of protocol therapy
- Anticoagulants within 14 days prior to Day 1 of protocol therapy or active
thromboembolism. The use of ASA or NSAIDS is allowed
- Live vaccines within 14 days prior to the first dose of study treatment. Seasonal flu
vaccines that do not contain live viruses are allowed. Examples of live vaccines
include, but are not limited to, the following: measles, mumps, rubella, chicken pox,
yellow fever, rabies, bacille Calmette Guerin, and typhoid (oral) vaccine. Seasonal
influenza vaccines for injection are generally killed virus vaccines and are allowed.
Intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines and are
not allowed
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition (including aluminum) to study agent
- Hypersensitivity to any study agent, or its excipients, when administered alone
- History of Posterior Reversible Encephalopathy Syndrome (PRES)
- Issues with tolerating oral medication (e.g. inability to swallow pills, malabsorption
issues, ongoing nausea or vomiting)
- Active diarrhea
- Clinically significant uncontrolled illness or medical disorder, nonmalignant systemic
disease, or active, uncontrolled infection. Examples include, but are not limited to,
uncontrolled ventricular arrhythmia, recent (90 days) myocardial infarction,
uncontrolled major seizure disorder, unstable spinal cord compression, superior vena
cava syndrome, or any psychiatric order that prohibits obtaining informed consent
- Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
- Other active malignancy
- Females only: Pregnant or breastfeeding
- Major surgery (other than debulking or exploratory surgery for ovarian cancer) for any
reason within 3 weeks prior to randomization and/or incomplete recovery from surgery
- Prior organ transplantation including allogenic stem cell transplantation
- Diagnosis of Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML)
- Known leptomeningeal disease, carcinomatous meningitis, or radiologic signs of CNS
hemorrhage. Known symptomatic brain metastases requiring steroids. Patients with
previously diagnosed brain metastases are eligible if they have completed their
treatment and have recovered from the acute effects of radiation therapy or surgery
prior to study enrollment, have discontinued corticosteroid treatment for these
metastases for at least 4 weeks and are neurologically stable
- Active infections
- Any other condition that would, in the Investigator's judgment, contraindicate the
patient's participation in the clinical study due to safety concerns with clinical
study procedures
- Patients must not have uncontrolled hypertension as defined by systolic blood pressure
(SBP) >= 160mmHg or diastolic blood pressure (DBP) >= 90mmHg; patients whose blood
pressure can be controlled medically are allowed to be rescreened once BP is under
control
- Prospective participants who, in the opinion of the investigator, may not be able to
comply with all study procedures (including compliance issues related to
feasibility/logistics)
|
