PRIMARY OBJECTIVES:
I. To estimate the progression-free survival (PFS) hazard ratio of the combination of weekly paclitaxel with vs without wild-type reovirus in patients with persistent or recurrent ovarian, fallopian tube, or primary peritoneal cancer.
II. To determine the frequency and severity of adverse events associated with these regimens as assessed by CTCAE v4.0.
SECONDARY OBJECTIVES:
I. To estimate the progression-free survival and overall survival of patients treated with weekly paclitaxel alone and weekly paclitaxel with REOLYSIN.
II. To estimate (and compare) the proportion of patients who respond to the regimen on each arm of the study (according to RECIST 1.1 with measurable patients and by CA-125 for those patients with detectible disease only).
III. To characterize and compare progression-free survival and overall survival in patients with measurable disease (RECIST 1.1 criteria) and patients with detectable (non-measurable) disease.
OUTLINE: This is a multicenter study. Patients are stratified according to their platinum-free interval (=< 182 days vs > 182 days) and measurable disease status (measurable vs non-measurable or detectable). Patients are randomized to 1 of 2 treatment arms
ARM I: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15.
ARM II: Patients receive paclitaxel as in arm I and wild-type reovirus IV over 1 hour on days 1-5.
In both arms, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Inclusion Criteria:
- Histologically confirmed diagnosis of ovarian epithelial, fallopian tube, or primary peritoneal cancer
- Recurrent or persistent disease
- Measurable or detectable (non-measurable) disease
- Measurable disease is defined as ≥ 1 lesion that can be accurately measured in 1 dimension (longest diameter to be recorded) as ≥ 10 mm by CT scan, MRI, or caliper measurement by clinical exam or as ≥ 20 mm when measured by chest x-ray; lymph nodes must be ≥ 15 mm in short axis when measured by CT scan or MRI
- Patients with measurable disease must have ≥ 1 "target lesion" to be used to assess response to study treatment as defined by RECIST 1.1 (tumors within a previously irradiated field will be designated as "non-target" lesion unless progression is documented or a biopsy is obtained to confirm persistence ≥ 90 days after completion of radiotherapy)
- Detectable disease is defined as not having measurable disease, but having ≥ 1 of the following conditions:
- Baseline values of CA-125 ≥ 2 times upper limit of normal (ULN)
- Ascites and/or pleural effusion attributed to tumor
- Solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions
- Not eligible for a higher priority GOG study, if one exists (in general, this would refer to any active GOG phase III protocol or Rare Tumor protocol for the same patient population)
- Received one prior 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) , or extended therapy administered after surgical or non-surgical assessment
- If patients were treated with paclitaxel for their primary disease, the paclitaxel may have been administered weekly or every 3 weeks
- GOG performance status (PS) 0-2 (for patients who have received one prior regimen) OR GOG PS 0-1 (for patients who have received two or three prior regimens)
- ANC ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 9 g/dL
- Creatinine ≤ 1.5 times ULN
- Bilirubin ≤ 1.5 times ULN
- SGOT ≤ 3 times ULN
- Alkaline phosphatase ≤ 2.5 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Patients must be able to avoid direct contact with severely immune-compromised individuals such as patients who have had a recent bone-marrow or organ transplant or patients with AIDS; contact should be avoided on the days of REOLYSIN treatment and for the 2 days following REOLYSIN treatment
- Patients must be able to avoid direct contact with pregnant or nursing women and infants while receiving REOLYSIN; contact should be avoided on the days of REOLYSIN treatment and for the 2 days following REOLYSIN treatment
- Sensory and motor neuropathy ≤ grade 1
- No clinically significant cardiovascular disease, including any of the following:
- Myocardial infarction or unstable angina within the past 6 months
- History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or cardiac arrhythmias requiring antiarrhythmic mediations (except for atrial fibrillation that is well controlled with antiarrhythmic medication)
- Troponin I > ULN
- Baseline ejection fraction ≤ 50% as assessed by ECHO or MUGA
- NYHA class II-IV congestive heart failure
- History of cerebrovascular accident, transient ischemic attack, or subarachnoid hemorrhage within the past 6 months
- No history of other invasive malignancies within the past 3 years except for nonmelanoma skin cancer
- No history of primary endometrial cancer unless all of the following criteria are met:
- Stage not greater than IB
- No more than superficial myometrial invasion without vascular or lymphatic invasion
- No poorly differentiated subtypes, including papillary serous, clear cell, or other FIGO grade 3 lesions
- No known HIV or hepatitis B or C
- No active infection requiring antibiotics (except for uncomplicated urinary tract infection)
- No concurrent acetaminophen (if receiving wild-type reovirus)
- No prior wild-type reovirus or other oncolytic virus
- No prior cancer treatment that contraindicates study treatment
- Two additional cytotoxic regimens for management of recurrent or persistent disease allowed, with ≤ 1 non-platinum, non-taxane regimen
- No prior weekly paclitaxel for recurrent or persistent disease
- Biologic/targeted (non-cytotoxic) therapy as part of the primary treatment regimen or as part of treatment for recurrent or persistent disease allowed
- Prior non-cytotoxic therapy alone not counted as prior regimen
- No prior non-cytotoxic therapy for recurrent or persistent disease
- Patients who have received only one prior cytotoxic regimen (platinum-based regimen for management of primary disease) must meet one of the following criteria:
- Platinum-free interval of < 12 months
- Progressed during platinum-based therapy
- Have persistent disease after a platinum-based therapy
- Recovered from effects of recent surgery, radiotherapy, or chemotherapy
- No prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the past 3 years
- Prior radiotherapy for localized cancer of the breast, head and neck, or skin is allowed provided that it was completed > 3 years ago and that the patient remains free of recurrent or metastatic disease
- No prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the past 3 years
- Prior adjuvant chemotherapy for localized breast cancer is allowed provided that it was completed > 3 years ago and that the patient remains free of recurrent or metastatic disease
- At least 3 weeks since prior therapy directed at the malignant tumor, including chemotherapy, biologic/targeted and immunologic agents
- At least 1 week since prior hormonal therapy directed at the malignant tumor
- Concurrent hormone replacement therapy allowed
- No concurrent immunosuppressive therapy, including chronic oral steroids (at an equivalent dose of > 5 mg/day of prednisone)
- No other concurrent investigational therapy, immunotherapy, or chemotherapy
Last updated: 03/04/2013
NCT ID: NCT01199263
IRB Number:12-002613
Find Mayo Clinic on