Sorafenib With or Without Paclitaxel and Carboplatin in Treating Patients With Recurrent Ovarian Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

Conditions: Recurrent Primary Peritoneal Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma

Treatments: Drug: Carboplatin; Drug: Sorafenib Tosylate; Drug: Paclitaxel

Study type: Interventional

Funder types: NIH

Identifiers

NCT00096200

U01CA062502 (U.S. NIH Grant/Contract)

CASE 2804

CDR0000390331

NCI-2009-00067 (Registry Identifier)

6557 (Other Identifier)

N01CM62208 (U.S. NIH Grant/Contract)

P30CA043703 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 44 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

44 participants in 2 patient groups

Arm I (closed to accrual 10/10/2008)

Experimental group

Description:

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

Treatment:

Drug: Sorafenib Tosylate

Arm II

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Sorafenib Tosylate

Drug: Carboplatin