Sorafenib in Treating Patients With Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Peritoneal Cancer in at Least the Second Remission

Study Overview
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Brief Summary
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RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. PURPOSE: This phase II trial is studying how well sorafenib works in treating patients with ovarian epithelial cancer, fallopian tube cancer, or peritoneal cancer in at least the second remission.

Detailed Description
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OBJECTIVES: Primary To determine the 12-month progression-free survival (PFS) rate of women with ovarian epithelial, fallopian tube, or peritoneal cancer in second or greater remission treated with oral sorafenib tosylate. Secondary To determine the safety and tolerability of prolonged treatment with oral sorafenib tosylate in women with a history of recurrent ovarian cancer. To correlate serum markers of angiogenesis (i.e., VEGF and bFGF) and tumor markers pAKT, HIF-1 α , and VEGF with 12-month PFS. OUTLINE: Patients receive oral sorafenib twice a day on days 1-28. Treatment repeats every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients undergo tumor tissue and blood sample collection at baseline, every 12 weeks during study, and after completion of study therapy for pharmacokinetic studies. Samples are analyzed for soluble markers of angiogenesis (i.e., VEGF and bFGF) via ELISA and HIF-1 α, VEGF, and pAKT via IHC staining. After completion of study treatment, patients are followed at 4 weeks.

Official Title
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A Phase II Trial of Oral Sorafenib (Bay43-9006) In Women With Epithelial Ovarian, Fallopian Tube Or Peritoneal Carcinoma In Second Or Greater Remission

Conditions
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Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cavity Cancer

Intervention / Treatment
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* Drug: sorafenib tosylate
* Other: immunoenzyme technique
* Other: immunohistochemistry staining method
* Other: laboratory biomarker analysis
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed epithelial carcinoma arising in the ovary, fallopian tube, or peritoneum Any stage and grade at diagnosis Must have received initial cytoreductive surgery and chemotherapy with ≥ 1 platinum-based chemotherapy regimen Persistent or recurrent disease after initial therapy In complete clinical remission after chemotherapy for recurrent disease, meeting all of the following criteria: CA125 ≤ 35 units/L Normal physical examination No definite evidence of disease by CT scan of the abdomen and pelvis Lymph nodes and/or soft tissue abnormalities ≤ 1.0 cm are not considered definite evidence of disease No known brain metastases PATIENT CHARACTERISTICS: Inclusion criteria: Karnofsky performance status 70-100% Life expectancy > 3 months ANC ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 9.0 g/dL INR < 1.5 OR PT/PTT within normal limits Creatinine ≤ 1.5 times upper limit of normal (ULN) Urinalysis negative for protein If urinalysis shows 1+ protein by dipstick or protein ≥ 30-100 mg/dL by semi-quantitative assay, a 24-hour urine collection is required Eligible patients must have a total urinary protein ≤ 500 mg AND measured creatinine clearance ≥ 50 mL/min from a 24-hour urine collection Bilirubin ≤ 1.5 times ULN AST and ALT ≤ 2.5 times ULN Alkaline phosphatase ≤ 2.5 times ULN Stable blood pressure (BP) measurement required on 3 separate days prior to the start of treatment No peripheral neuropathy > grade 1 Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Exclusion criteria: Other invasive malignancies within the past 5 years, except nonmelanoma skin cancer Uncontrolled concurrent illness or medical condition including, but not limited to, any of the following: Ongoing or active infection Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia Uncontrolled diabetes Psychiatric illness or social situation that would preclude study compliance Uncontrolled hypertension defined as a persistent BP > 150/100 mm Hg (or a persistent BP > 180/90 mm Hg if the patient has a history of isolated systolic hypertension) despite ≥ 2 attempts at antihypertensive medication dosage adjustment ≥ 2 weeks apart Thrombolic or embolic events such as cerebrovascular accident, including transient ischemic attack, within the past 6 months Pulmonary hemorrhage or bleeding event ≥ grade 2 within 4 weeks of the first dose of study drug Other hemorrhage or bleeding event ≥ grade 3 within 4 weeks of the first dose of study drug Serious nonhealing wound, ulcer, or bone fracture Evidence or history of bleeding diathesis or coagulopathy Inability to take oral medications or gastrointestinal condition that compromises absorption History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib tosylate PRIOR CONCURRENT THERAPY: Inclusion criteria: See Disease Characteristics No prior sorafenib tosylate or other inhibitors of MAPK signaling intermediates or angiogenesis inhibitors No prior cancer treatment that would contraindicate protocol therapy More than 4 weeks since prior radiotherapy More than 3 weeks since prior chemotherapy, biological therapy, or immunotherapy More than 1 week since prior hormonal therapy for cancer treatment Exclusion criteria: Major surgery (i.e., laparotomy) within the past 4 weeks or minor surgery within the past 2 weeks Placement of a vascular access device is not considered minor surgery Concurrent combination antiretroviral therapy for HIV-positive patients Concurrent St. John wort, rifampin, or enzyme-inducing anticonvulsants (e.g., carbamazepine, phenytoin, or phenobarbital)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral Sorafenib (BAY43-9006)<br>Sorafenib is supplied as 200-mg tablets. Sorafenib will be administered as 400 mg orally daily x 28 days (continuous). One cycle = 28 days. There is no planned treatment interruption between cycles. Sorafenib should be taken without food (at least 1 hour before or 2 hours after eating). In the absence of intolerable toxicity, a patient may continue to receive treatment with sorafenib until disease progression, or until 24 months have elapsed. | Drug: sorafenib tosylate<br> <br> Other: immunoenzyme technique<br> <br> Other: immunohistochemistry staining method<br> <br> Other: laboratory biomarker analysis<br> <br> Other: pharmacological study<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) Rate at 12 Months | All 5 patients experienced a rash. As a result, all 5 were either advised to withdraw from the protocol, or withdrew themselves from the protocol. The outcome was not met. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent ovarian epithelial cancer, fallopian tube cancer, primary peritoneal cavity cancer, stage I ovarian epithelial cancer, stage II ovarian epithelial cancer, stage III ovarian epithelial cancer, stage IV ovarian epithelial cancer