Ovarian Cancer
Conditions
Brief 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.
Interventions
DRUGHydroxychloroquine
3 x 200 milligram tablets twice daily
DRUGNelfinavir
2x 625 milligram tablets twice daily
DRUGBevacizumab
IV 15 milligram/kilogram every 3 weeks
Sponsors
Medical University of South Carolina
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 upon ECG. * Patients who have diabetes mellitus must have it well-controlled (A1c of \<8%).
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of combination of study drugs | 6 months | To measure the safety of HCQ + NFV in combination with standard-of-care maintenance bevacizumab in patients with high-grade serous ovarian cancer. DLT (dose limiting toxicity) is the standard endpoint in evaluating safety at this study phase. Will monitor adverse events per CTCAE v5.0. |
| Evaluation of Anti Tumor Activity | 6 months | Evaluate the anti-tumor activity of HCQ + NFV in combination with standard-of-care maintenance bevacizumab in patients with high-grade serous ovarian cancer. Measured by 6-month progression-free survival rate, a composite metric based on CA 125 and radiographic imaging. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in CA125 | 6 months | changes in CA125 in patients treated with HCQ + NFV in combination with standard-of-care maintenance bevacizumab |
| Changes in Quality of Life | 6 months | To document the change in QOL (via disease-specific FACT questionnaire, composite score) in patients treated with HCQ + NFV in combination with standard-of-care maintenance bevacizumab |
Countries
United States
Contacts
Primary ContactBrian Orr
Outcome results
None listed