GOG 3003: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE II STUDY OF VTX-2337 (IND #78,416) IN COMBINATION WITH PEGYLATED LIPOSOMAL DOXORUBICIN (PLD) IN PATIENTS WITH RECURRENT OR PERSISTENT EPITHELIAL OVARIAN, FALLOPIAN TUBE OR PRIMARY PERITONEAL CANCER

Summary

This is a randomized, blinded, placebo-controlled, two-arm phase ii design.

The primary analysis will be of overall survival using a log rank test stratified by the randomization strata: treatment free interval ([LessThanorequalTo] 6 months versus [Greater Than] 6 to 12 months) and GoG performance status (0 versus 1).

Treatment arms:
Treatment assignment will be blinded and assigned in a randomized manner.
arm 1: PLD 40 mg/m2 plus VTX-2337 3.0 mg/m2
arm 2: PLD 40 mg/m2 plus placebo

The dosing schedule will be the same for both treatment arms, and will be based on a 28-day cycle. The starting dose schedule is PLD on Day 1 plus VTX-2337 or placebo on Day 3, Day 10, and Day 17 for the first 4 cycles (induction schedule). Starting with cycle 5, the dose regimen will be PLD on Day 1 plus VTX-2337 or placebo on Day 3 only, without additional doses of VTX-2337 or placebo on Days 10 and Day 17.

The blinded treatment cycle is repeated every 28 days until disease progression (based on immune-Related ReCiST) or until adverse effects prohibit further therapy.

The randomization will be stratified using blocked randomization, and will be done in a 1:1 ratio to one of the following arms:
arm 1: PLD 40 mg/m2 plus VTX-2337 3.0 mg/m2
arm 2: PLD 40 mg/m2 plus placebo

Participant Eligibility

3.11 Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. Histologic documentation of the original primary tumor is required via pathology report.
3.12 Patients with the following histologic cell types are eligible: serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial adenocarcinoma, transitional cell carcinoma, malignant Brenner's tumor or adenocarcinoma not otherwise specified (N.O.S.).
3.13 Patient must have measurable disease as defined by RECIST 1.1 (section 8.11). Measurable disease is at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be >= 10 mm when measured by CT, MRI, or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray. Lymph nodes must be >= 15 mm in short axis when measured by CT or MRI.
Patients must have at least one
* target lesion
* as defined by RECIST 1.1. Tumors within a previously irradiated field will be designated as
* non-target
* lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
3.14 Patients must have received treatment with a platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin or another organoplatinum compound. This initial treatment may have included intraperitoneal therapy, consolidation, non-cytotoxic agents (biologic/targeted therapy) or extended therapy administered after surgical or non-surgical assessment.
Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease.
Patients are allowed to have received, but are not required to have received, biologic/targeted therapy (e.g., bevacizumab and/or PARP inhibitor) as part of their primary treatment regimen or for management of recurrent or persistent disease.
3.15 Patients must have platinum-resistant disease, defined as progression < 12 months after completion of first- or second-line platinum-based chemotherapy. The date (platinum-free interval) should be calculated from the last administered dose of platinum therapy.
Patients with platinum-refractory primary disease, defined as having disease progression while receiving first-line platinum-based chemotherapy, are NOT eligible. Disease progression while receiving second-line platinum therapy is allowed.
3.16 Patients must have adequate bone marrow, renal, hepatic, and neurologic functions as defined by the following:
3.161 Bone marrow function:

*
Absolute neutrophil count (ANC) >= 1,500/mm3

*
Platelets >= 100,000/mm3

*
Hemoglobin >= 9 g/dL
3.162 Renal function: creatinine <= 1.5 x institutional upper limit normal (ULN).
3.163 Hepatic function:

*
Bilirubin < 1.2 mg/dL

*
SGOT (AST) and SGPT (ALT) <= 3.0 x ULN

*
Alkaline phosphatase <= 2.5 x ULN
3.17 Patients must have recovered from effects of recent surgery, radiotherapy or chemotherapy:
3.171 Patients should be free of active infection requiring parenteral antibiotics.
3.172 Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to the first date of treatment on this study. Continuation of hormone replacement therapy is permitted.
3.173 Any other prior therapy directed at the malignant tumor, including chemotherapy, biologic/targeted agents and immunologic agents, must be discontinued at least three weeks prior to the first date of treatment on this study.
3.174 Any prior radiation therapy must be completed at least four weeks prior to the first date of treatment on this this study.
3.18 Patients must have a GOG performance status of 0 or 1.
3.19 Patients of childbearing potential must have a negative pregnancy test prior to the study entry and be practicing an effective form of contraception. If applicable, patients must discontinue breastfeeding prior to the first date of treatment on this study.
3.110 Patients must meet the entry requirements and undergo the baseline procedures specified in section
3.111 Patients must have signed an IRB-approved informed consent form and authorization permitting release of personal health information.