CPI-0209 in Combination with Carboplatin for the Treatment of Patients with Platinum Sensitive Recurrent Ovarian, Fallopian Tube or Primary Peritoneal Cancer

Inclusion Criteria

• Women ≥ 18 years old with platinum-sensitive recurrent ovarian, fallopian or primary peritoneal cancer (defined as recurrent disease > 6 months after completing last platinum- based chemotherapy) that are eligible to receive platinum-based chemotherapy)
• Documented disease recurrence/progression based on Gynecological Cancer Intergroup (GCIG)-Response Evaluation Criteria in Solid Tumors (RECIST)
• Must have had at least 1 prior line of platinum-based therapy, prior bevacizumab or poly (ADP-ribose) polymerase inhibitor (PARPi) use are allowed. Women with germline BRCA mutations should be considered for PARPi maintenance as standard of care treatment prior to consideration of clinical trial enrollment
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 with life expectancy of ≥ 3 months
• Serum creatinine ≤ 1.5mg/dL or 24-hour clearance ≥ 50mL/min
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 x upper limit of normal (ULN) (or < 5 x ULN if liver metastasis are present)
• Total bilirubin ≤ ULN or total bilirubin ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN in patients with well-documented Gilbert's syndrome
• Hemoglobin ≥ 9 gm/dl
• Platelets ≥ 100,000/ul
• Absolute neutrophil count (ANC) ≥ 1500/ul
• International normalized ratio (INR) ≤ 1.5
• Potassium, total calcium (corrected for serum albumin) and sodium within normal limits for the institution or corrected to within normal limits with supplements before first dose of study medication. Grade 1 hypomagnesemia is allowable
• Must be able to swallow CPI-0209 tablet/oral suspension
• Able to provide informed consent and comply with all study protocol
• Treated central nervous system (CNS) metastasis allowed if treatment is completed ≥ 8 weeks prior to enrollment. Patients must be asymptomatic off systemic corticosteroids for at least 4 weeks after completion of radiation therapy. CNS disease must be stable or regressed on repeat imaging performed at least 4 weeks after completion of therapy
• Women of child-bearing potential (those who have had a menstrual cycle within the last year and have not had a tubal ligation or surgical removal of both ovaries and/or hysterectomy) and their partners must agree to abstain from vaginal intercourse or use and continue highly effective methods of contraception for at least 183 days after discontinuation of study treatment. * Total abstinence when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception * Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment. * Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that patient * Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception * In case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment * Note: Oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception due to unknown effect of drug-drug interaction. Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment is she considered not of childbearing potential

Exclusion Criteria

• Borderline or low malignant potential histology
• Platinum-resistant disease (as defined as progressive disease [PD] within 6 months of completion of chemotherapy with a platinum agent)
• Known hypersensitivity to any of the excipients of CPI-0209
• Gastrointestinal (GI) dysfunction or disease that may significantly alter the absorption of the study drugs
• Concurrent malignancy or malignancy within 3 years prior to starting study drug with the exception of adequately treated basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer or per physician discretion that the previous cancer was adequately treated with curative intent and unlikely to recur (the study principal investigator [PI] must concur with this determination)
• History of HIV infection
• Has an active infection requiring systemic treatment
• Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator’s judgment, cause unacceptable safety risks and contraindicate patient’s participation in the clinical study or compromise compliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections, significant cardiac/pulmonary disease etc.)
• Patient is currently receiving warfarin or other coumadin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH) or fondaparinux is allowed
• Use of herbal supplements unless discontinued ≥ 7 days prior to initiation of study drug
• Consumption of foods which are strong inducers or inhibitors of CYP3A4/5 has to be discontinued 7 days prior to initiation of study drug. Patients that are unwilling to exclude Seville oranges, grapefruit juice, AND grapefruit from the diet and all foods that contain those fruits from time of enrollment to through the duration of study participation will be excluded
• Pregnant or breast feeding
• Participation in a prior investigational study within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer
• Patient who has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug, and who has not recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia) and/or in whom ≥ 25% of the bone marrow (Ellis, 1961) was irradiated
• Patient has had major surgery within 4 weeks prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered as major surgery)
• Patient has not recovered from all toxicities related to prior anticancer therapies to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5 grade ≤ 1 (exception to this criterion: patients with any grade of alopecia, controlled endocrine toxicities and/or neuropathy ≤ grade 2 are allowed to enter the study)
• Grade 3 baseline neuropathy
• Patient with a Child-Pugh score B or C