Recurrent Fallopian Tube Carcinoma, Recurrent Ovarian Carcinoma, Recurrent Primary Peritoneal Carcinoma
Conditions
Brief summary
Sorafenib may stop the growth of tumor cells by blocking the enzymes necessary for their growth and by stopping blood flow to the tumor. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving sorafenib together with chemotherapy may kill more tumor cells. This randomized phase II trial is studying how well giving sorafenib together with paclitaxel and carboplatin works in treating patients with recurrent ovarian cancer, primary peritoneal cancer, or fallopian tube cancer. (Sorafenib only group closed as of 10/10/2008).
Detailed description
PRIMARY OBJECTIVES : I. Compare the progression-free and overall survival rate of patients with recurrent platinum-sensitive ovarian epithelial, primary peritoneal, or fallopian tube cancer treated with sorafenib with or without carboplatin and paclitaxel. (Arm I \[sorafenib only\] closed to accrual 10/01/2008) II. Evaluate the response rate and time to disease progression in patients treated with these regimens. OUTLINE: This is a multicenter study. Patients are stratified according to performance status and participating center. ARM I (closed to accrual 10/01/2008): Patients receive oral sorafenib twice daily on days 1-28.Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression crossover to arm II. ARM II: Patients receive oral sorafenib twice daily on days 2-19. Patients also receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Interventions
DRUGCarboplatin
Given IV
DRUGPaclitaxel
Given IV
DRUGSorafenib Tosylate
Given orally
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of ovarian epithelial, primary peritoneal, or fallopian tube cancer * Recurrent disease * Must have received a prior platinum-based regimen * Platinum-sensitive (treatment-free interval \> 6 months) * No more than 2 prior chemotherapy regimens * Measurable disease * At least 1 unidimensionally measurable lesion \>= 20 mm by conventional techniques OR \>= 10 mm by spiral CT scan * Not in a prior irradiation field * No known brain metastases * Performance status: * ECOG 0-2 OR * Karnofsky 80-100% * Life expectancy: * More than 12 weeks * Hematopoietic: * Absolute neutrophil count \>= 1,500/mm3 * Platelet count \>= 100,000/mm3 * Hemoglobin \>= 9 g/dL * No bleeding diathesis * Hepatic: * Bilirubin \< 1.5 times upper limit of normal (ULN) * AST or ALT =\< 2 times ULN * No history of allergic reaction attributed to compounds of similar chemical or biological composition to sorafenib or other agents used in the study * Patients who have had a reaction to a taxane or a platinum and have not yet been rechallenged may undergo a desensitization regimen on study * No hypersensitivity to paclitaxel or drugs using the vehicle Cremophor El: * Prior hypersensitivity reaction to paclitaxel allowed provided rechallenged successfully * Renal: * Creatinine \< 2 mg/dL * Cardiovascular: * Abnormal cardiac conduction (e.g., bundle branch block or heart block) allowed if stable for the past 6 months * No symptomatic congestive heart failure * No uncontrolled hypertension * No cardiac arrhythmia * No unstable angina pectoris; * No myocardial infarction within the past 6 months * Negative pregnancy test * Fertile patients must use effective contraception * Adequate intestinal function * No concurrent requirements for IV hydration or nutritional support * No active or ongoing infection * No psychiatric illness or social situation that would preclude study compliance * No other concurrent uncontrolled illness * No other invasive malignancy with the past 5 years except nonmelanoma skin cancer * More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered * More than 3 weeks since prior hormonal therapy * More than 4 weeks since prior radiotherapy and recovered * No prior sorafenib * No prior anticancer therapy that contraindicates study therapy * No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine, or phenobarbital), rifampin, or Hypericum perforatum (St. John's wort) * No concurrent combination antiretroviral therapy for HIV-positive patients * No concurrent therapeutic anticoagulation therapy * Concurrent prophylactic low-dose warfarin allowed for maintenance of venous or arterial access devices * No other concurrent anticancer therapies * No other concurrent investigational agents * Not pregnant or nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete and Partial Response Rate Using the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | after 6 weeks (2 cycles) | Patients should be reevaluated for response every 2 cycles (6 weeks). Patients who continue on Arm A of treatment for more than 12 months should be reevaluated for response every 3 cycles (9 weeks). In addition to a baseline scan, confirmatory scans should also be obtained 4 weeks following initial documentation of objective response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the Progression-free Survival Rate | up to 85 months of follow-up | Progression free survival (PFS) was measured by months from the date of treatment to the date of death or the date of progression, and censored at the date of last follow-up for those alive without progression. |
| Overall Survival | up to 85 months of follow-up | Overall survival time, in months, is calculated from the date of treatment to date of death, and to date of last follow-up for those still alive. |
Countries
United States
Participant flow
Recruitment details
Patients accrued from medical clinic from August 2004 through June 2011
Participants by arm
| Arm | Count |
|---|---|
| Arm A Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression crossover to arm II | 9 |
| Arm B Patients receive oral sorafenib twice daily on days 2-19. Patients also receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. | 30 |
| Arm C Patients from Arm A that had progressive disease were eligible to crossover to Arm B | 5 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 4 | 0 |
| Overall Study | Ineligible pathology | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 0 |
Baseline characteristics
| Characteristic | Arm A | Arm B | Arm C | Total |
|---|---|---|---|---|
| Age, Customized Age 40-49 | 0 participants | 2 participants | 0 participants | 2 participants |
| Age, Customized Age 50-59 | 4 participants | 15 participants | 0 participants | 19 participants |
| Age, Customized Age 60-69 | 4 participants | 8 participants | 5 participants | 17 participants |
| Age, Customized Age 70-79 | 1 participants | 5 participants | 0 participants | 6 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 22 Participants | 5 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 8 Participants | 0 Participants | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 5 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) White | 9 Participants | 24 Participants | 5 Participants | 38 Participants |
| Region of Enrollment United States | 9 participants | 30 participants | 5 participants | 44 participants |
| Sex: Female, Male Female | 9 Participants | 30 Participants | 5 Participants | 44 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 13 | 29 / 29 | 5 / 5 |
| serious Total, serious adverse events | 3 / 14 | 5 / 30 | 2 / 5 |
Outcome results
Primary
Complete and Partial Response Rate Using the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
Patients should be reevaluated for response every 2 cycles (6 weeks). Patients who continue on Arm A of treatment for more than 12 months should be reevaluated for response every 3 cycles (9 weeks). In addition to a baseline scan, confirmatory scans should also be obtained 4 weeks following initial documentation of objective response.
Time frame: after 6 weeks (2 cycles)
Population: Patients that received 2 cycles of treatment. Includes results from patients that crossed over to Arm C.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A | Complete and Partial Response Rate Using the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Partial Response | 2 participants |
| Arm A | Complete and Partial Response Rate Using the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Progressive Disease | 8 participants |
| Arm A | Complete and Partial Response Rate Using the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Stable Disease | 3 participants |
| Arm A | Complete and Partial Response Rate Using the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Complete Response | 0 participants |
| Arm B | Complete and Partial Response Rate Using the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Complete Response | 4 participants |
| Arm B | Complete and Partial Response Rate Using the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Partial Response | 11 participants |
| Arm B | Complete and Partial Response Rate Using the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Stable Disease | 7 participants |
| Arm B | Complete and Partial Response Rate Using the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Progressive Disease | 1 participants |
| Arm C: Crossover From Arm A to B | Complete and Partial Response Rate Using the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Complete Response | 0 participants |
| Arm C: Crossover From Arm A to B | Complete and Partial Response Rate Using the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Progressive Disease | 0 participants |
| Arm C: Crossover From Arm A to B | Complete and Partial Response Rate Using the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Stable Disease | 4 participants |
| Arm C: Crossover From Arm A to B | Complete and Partial Response Rate Using the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Partial Response | 1 participants |
Secondary
Evaluate the Progression-free Survival Rate
Progression free survival (PFS) was measured by months from the date of treatment to the date of death or the date of progression, and censored at the date of last follow-up for those alive without progression.
Time frame: up to 85 months of follow-up
Population: Subjects who completed at least 2 cycles of therapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A | Evaluate the Progression-free Survival Rate | 5.6 months |
| Arm B | Evaluate the Progression-free Survival Rate | 16.8 months |
| Arm C: Crossover From Arm A to B | Evaluate the Progression-free Survival Rate | 16.8 months |
Secondary
Overall Survival
Overall survival time, in months, is calculated from the date of treatment to date of death, and to date of last follow-up for those still alive.
Time frame: up to 85 months of follow-up
Population: Subjects that received at least 2 cycles of treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A | Overall Survival | 25.6 months |
| Arm B | Overall Survival | 25.9 months |
| Arm C: Crossover From Arm A to B | Overall Survival | 25.9 months |