A Randomized Phase IIB Evaluation of Weekly Paclitaxel (NSC #673089) Plus Pazopanib (NSC #737754) Versus Weekly Paclitaxel Plus Placebo in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Laboratory Biomarker Analysis
- Conditions
- Recurrent Fallopian Tube Carcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 106
- Locations
- 142
- Primary Endpoint
- Progression Free Survival
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This randomized phase II trial studies how well paclitaxel when given together with or without pazopanib hydrochloride works in treating patients with ovarian epithelial, fallopian tube, or peritoneal cavity cancer that is persistent or has come back. Drugs used in chemotherapy, such as paclitaxel work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Pazopanib hydrochloride may stop the growth of tumor cells by blocking blood flow to the tumor or by blocking some of the enzymes needed for cell growth. It is not yet known whether paclitaxel is more effective when given with or without pazopanib hydrochloride in treating ovarian epithelial, fallopian tube, and peritoneal cavity cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To estimate the progression-free survival hazard ratio of the combination of weekly paclitaxel and pazopanib (pazopanib hydrochloride) compared to weekly paclitaxel and placebo in patients with persistent or recurrent ovarian, fallopian tube, or primary peritoneal cancer. SECONDARY OBJECTIVES: I. To determine the frequency and severity of adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE). II. To estimate and compare the proportion of patients responding to therapy by Response Evaluation Criteria in Solid Tumors (RECIST), cancer antigen 125 (CA125) response, the overall survival (OS), and the duration of response in each arm. TERTIARY OBJECTIVES: I. To explore the association between plasma cytokines and angiogenic markers and progression-free and overall survival. II. To explore the association between single-nucleotide polymorphisms (SNPs) and progression-free and overall survival. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15 and placebo orally (PO) daily on days 1-28. ARM II: Patients receive paclitaxel as in Arm I and pazopanib hydrochloride PO daily on days 1-28. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma; histologic documentation of the original primary tumor is required via the pathology report
- •Patients must have measurable disease or non-measurable (detectable) disease
- •Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be greater than or equal to 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI), or caliper measurement by clinical exam; or greater than or equal to 20 mm when measured by chest x-ray; lymph nodes must be greater than or equal to 15 mm in short axis when measured by CT or MRI
- •Non-measurable (detectable) disease in a patient is defined in this protocol as one who does not have measurable disease but has at least one of the following conditions:
- •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
- •Patients with measurable disease must have at least one "target lesion" to be used to assess response on this protocol 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
- •Patients must not be eligible for a higher priority Gynecology Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG phase III or Rare Tumor protocol for the same patient population; in addition, patients must not be eligible for the currently active phase II cytotoxic protocol in platinum resistant disease
- •Patients who have received one prior regimen must have a GOG performance status of 0, 1, or 2
- •Patients who have received two or three prior regimens must have a GOG performance status of 0 or 1
Exclusion Criteria
- •Patients who have had previous treatment with pazopanib; patients who have had previous treatment with weekly paclitaxel for recurrent or persistent disease
- •Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies are excluded if there is any evidence of other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
- •Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis within the last three years are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease
- •Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the last three years; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease
- •Patients with clinically significant cardiovascular disease; this includes:
- •Uncontrolled hypertension, defined as systolic greater than 140 mm Hg or diastolic greater than 90 mm Hg despite antihypertensive medications
- •Congenital long QT syndrome or baseline QTc greater than 480 milliseconds
- •Myocardial infarction or unstable angina within 6 months prior to registration
- •New York Heart Association (NYHA) class II or greater congestive heart failure
- •History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or serious cardiac arrhythmia requiring medication
Arms & Interventions
Arm I (paclitaxel and placebo)
Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and placebo PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Arm I (paclitaxel and placebo)
Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and placebo PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Paclitaxel
Arm I (paclitaxel and placebo)
Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and placebo PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Placebo
Arm II (paclitaxel and pazopanib hydrochloride)
Patients receive paclitaxel as in arm I and pazopanib hydrochloride PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Arm II (paclitaxel and pazopanib hydrochloride)
Patients receive paclitaxel as in arm I and pazopanib hydrochloride PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Paclitaxel
Arm II (paclitaxel and pazopanib hydrochloride)
Patients receive paclitaxel as in arm I and pazopanib hydrochloride PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Pazopanib Hydrochloride
Outcomes
Primary Outcomes
Progression Free Survival
Time Frame: For those patients whose disease can be evaluated by physical examination, progression was assessed prior to each 21-day cycle. CT scan or MRI if used to follow lesion for measurable disease every other cycle, Up to 5 years
The time from randomization until disease progression, death, or date of last contact. Endpoints are progression or death. Patients who are not observed with an endpoint are censored. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Secondary Outcomes
- Adverse Events as Assessed by CTCAE v.4(From baseline to 30 days after last dose of drug.)
- Proportion of Participants With Tumor Response by RECIST(Every other cycle for 6 months, then every 3 months until disease progression,Up to 5 years)
- Percentage of Participants With Tumor Response by CA-125(Prior to each cycle of treatment. Then follow-up every three months for 2 years and then every 6 months for 3 years, up to 5 years.)
- Overall Survival (OS)(Every cycle while patient is receiving protocol therapy. Patients monitored for survival after off therapy every 3 months for 2 years, then every 6 months, up to 5 years)