Phase II Study of ONC201 Plus Weekly Paclitaxel in Patients With Platinum-Resistant Refractory or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
This phase II trial studies the side effects of ONC201 and paclitaxel and how well they work in treating patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer that has come back (recurrent), or that does not respond to treatment (refractory). ONC201 is the first in its class of drugs that antagonize some specific cell receptors on cancer cells, leading to their destruction. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ONC201 and paclitaxel may work better in treating patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer compared to paclitaxel alone.
• Histologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal cancer.
• Progressed within 6 months of completing at least 1 cycle of last platinum containing regimen. Patients with refractory disease (progression during platinum-containing therapy) are eligible. This includes both adjuvant therapy and in the recurrent setting.
• No more than 4 prior treatment regimens defined as investigational, chemotherapy, hormonal, biologic, or targeted therapy in the platinum resistant setting and total of 7 prior regimens in all settings will be allowed. Prior maintenance therapy with biologic or targeted agent does NOT count as a treatment regimen (e.g. Maintenance bevacizumab, Parpi, or immunotherapy).
• At least one measurable lesion according to RECIST v1.1.
• For the eight patients enrolled for PK/PD. Availability of tissue from carcinoma. For most patients this will be archival tissue. If there is no archival tissue available, biopsy of lesion MUST be performed prior to initiation of therapy. Lesions must be available for biopsy as well in these patients.
• Any prior palliative radiation therapy must be completed at least 7 days prior to start of study treatment and patients must have recovered from any acute adverse effects prior to start of study treatment.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-1.
• Female patients who are not of childbearing potential and fertile female patients of childbearing potential who agree to use adequate contraceptive measures from 2 weeks prior to the study and until 1 month after study treatment discontinuation, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 3 days prior to start of study treatment.
• Patients must have adequate (at baseline):
‣ Bone marrow function: Absolute neutrophil count (ANC) ≥1,500/µL. Platelets
‣ ≥100,000/µL and hemoglobin \> 8.0 gm/dL, transfusion allowed up to 1 week prior to maintain Hgb \>8.
⁃ Renal function: Calculated creatinine clearance (CrCl) ≥35 mL/min/1.73 mm2
⁃ Hepatic function: Bilirubin less than or equal to 1.5 x ULN; alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase (ALT) less than or equal to 3 x ULN. AP, AST and ALT less than or equal to 5 x ULN is acceptable if patient has known hepatic metastasis