autophagy maintenance (automain)

Conditions: Ovarian Cancer

Summary: this is a single-institution, single-arm study with a safety lead-in to determine if previously established safe doses of autophagy drugs, hydroxychloroquine (hcq) and nelfinavir mesylate (nfv) will benefit ovarian cancer patients in a maintenance setting. patients will receive the two study drugs hcq and nfv in combination with maintenance bevacizumab.


Eligibility criteria:
inclusion criteria: * participants must have platinum-sensitive first recurrent high-grade serous or high-grade predominantly serous ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. patients must have had a 6-month disease-free progression since last platinum chemotherapy to be considered platinum sensitive. * all participants must agree to have previously undergone genetic testing with germline panel testing with at least brca 1/2 mutation status known and/or somatic tumor next generation sequencing with homologous recombination deficiency (hrd) testing and/or loss of heterozygosity (loh) known. * participants must be enrolled within 3-8 weeks of the first day of the last cycle of platinum-based chemotherapy for their first cancer recurrence. - participants must have received at least 3-courses of bevacizumab during chemotherapy and have a plan to continue maintenance bevacizumab therapy. * evidence of platinum-sensitive response to current platinum-based chemotherapy with a partial or complete response based on imaging or ca-125 trend * participants of childbearing potential must have a negative serum or urine pregnancy test (beta human chorionic gonadotropin \[hcg\]) within 7 days before receiving the first dose of study treatment. * voluntary, signed, and dated, institutional review board (irb) approved consent form per regulatory and institutional guidelines. * 18 years of age or older. * ecog performance status of 0-2 * bilirubin ≤ 1.5 times the upper limit of normal (uln) and ast / alt ≤ 3 times uln. subjects with gilbert's syndrome may be included if the total bilirubin is \< 3 times uln and the direct bilirubin is within normal limits. * crcl ≥35 ml/min, according to the cockgroft-gault formula. * absolute neutrophil count (anc) ≥ 1,000 cells/mm3. * platelet count ≥ 75,000 cells / mm3 * hemoglobin ≥ 9 g/ dl, recent transfusion is allowed, though must be ≥ 7 days c1d1 of investigational agents * adequately controlled blood pressure (\<160 mm hg/100 mm hg) as determined by the treating investigator. * subjects with the potential to produce children must agree to effective contraceptive method use during study participation and at least 6 months after discontinuation of the study. * patients requiring narcotic analgesics must be on stable doses for at least 2 weeks before study entry. * patients must discontinue any statin use within 48 hours of beginning study treatment. * patients must have a qt interval of \<450 ms on screening * patients who have well-controlled (a1c of \<8%) diabetes mellitus exclusion criteria: * new york heart association (nyha) class iii or iv cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or history of ischemia on baseline ecg. * underlying psychiatric disorder requiring hospitalization within the last two years. * clinically significant neurological disorder (parkinson's disease, dementia, multiple sclerosis), as determined by the enrolling investigator. * platinum resistant or refractory disease * active, uncontrolled bacterial, viral, or fungal infection, requiring systemic therapy. * treatment with local or systemic radiation therapy, surgery, or investigational therapy within 28 days before registration with the exception of the platinum doublet and bevacizumab. * unwillingness or inability to comply with procedures required in this protocol. * serious nonmalignant disease that could compromise protocol objectives in the opinion of the investigator. * patients who are receiving coumadin * patients who are currently participating in any other clinical trial of an investigational product. * any other mental incapacitation or psychiatric illness that would preclude study participation, as determined by the enrolling investigator. * prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled in this study. * female patients who are of child-bearing potential (wocbp) who are pregnant or planning to become pregnant during the study or within 6 months of the last dose of study drugs. a urine pregnancy test for wocbp will be collected during the screening period. females will be determined not to be of child-bearing potential with a history of hysterectomy, tubal ligation, dual salpingo-oophorectomy, or age 45 or older with postmenopausal status \> 12 months. * patients unable to stop taking strong inhibitors and inducers of cyp2c8, cyp3a4, cyp2c19, cyp2d6, fmo-1, and mao-a. * patients unable to stop taking substrates of cyp2d6, cyp3a4, p-gp, mate1k, and mate2k. * patients diagnosed with myasthenia gravis * patients with g6pd deficiency * patients with porphyria * platinum-sensitive patients that are candidates for parp inhibitor maintenance, patients will be allowed if previously did not tolerate parp and opt against parp maintenance * patients that have contraindications to bevacizumab, as per approved product labeling * patients that have a high ascvd score based on the american college of cardiology ascvd risk estimator plus calculator and who should not stop their statin due to cardiovascular risk