Paclitaxel and Carboplatin With Or Without Sorafenib In The First-Line Treatment Of Patients With Ovarian Cancer

Study Overview
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Brief Summary
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This trial will compare the efficacy and toxicity of standard first-line chemotherapy alone vs. standard chemotherapy plus sorafenib in patients with stage III/IV ovarian cancer following cytoreductive surgery. Patients with residual large volume disease and/or bowel involvement will be excluded, to minimize the risk of bowel perforation.

Detailed Description
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All patients must be at least 4 weeks from cytoreductive surgery before starting treatment. Patients will be randomized to receive treatment with either paclitaxel/carboplatin + sorafenib or paclitaxel/carboplatin. Paclitaxel/carboplatin will be repeated every 21 days for a maximum of 6 cycles. Patients with objective response/stable disease after completing 6 courses of chemotherapy will continue sorafenib until disease progression or for a total of 12 months. - Regimen A: Paclitaxel 175 mg/m2 1-3 hour IV infusion, Day 1 Carboplatin AUC 6 infused over 20 minutes IV, Day 1 Sorafenib 400mg PO bid - Regimen B: Paclitaxel 175mg/m2, 1-3 hour IV infusion, Day 1 Carboplatin AUC 6.0, 20 minute IV infusion, Day 1

Official Title
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A Randomized Phase II Study of Paclitaxel/Carboplatin With or Without Sorafenib in the First-Line Treatment of Patients With Stage III/IV Epithelial Ovarian Cancer

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: Sorafenib
* Drug: Paclitaxel
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed, stage III or IV epithelial ovarian carcinoma No previous treatment with chemotherapy or radiation therapy All patients must have undergone cytoreductive surgery, with the following results: No residual tumor nodule > 3cm No residual tumor involvement of the bowel (ie. invasion into bowel wall) No residual intestinal obstruction Measurable or evaluable disease. Patients with elevated CA-125 levels and/or evaluable disease per RECIST criteria are eligible. ECOG performance status 0 or 1. ANC ≥ 1500/µL, platelets ≥ 100,000/µL, hemoglobin ≥ 9.0 g/dL. Total bilirubin ≤ 1.5 x upper limits of normal (ULN), ALT and AST ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver metastases) Serum creatinine _ 1.5 x ULN INR < 1.5 or a PT/PTT within normal limits. Patients receiving anticoagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR may be > 1.5, and should be measured prior to initiation of sorafenib and monitored at least weekly until INR is stable in the desired therapeutic range. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to start of treatment. Patients must be able to understand the nature of this study and give written informed consent. Exclusion Criteria: Age < 18 years Active cardiac disease, including: A) congestive heart failure > class II NYHA , B) unstable angina or onset of angina within last 3 months, C) myocardial infarction within 6 months Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy Patients with CNS metastases. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis. Uncontrolled hypertension defined as systolic blood pressure > 150mmHg or diastolic pressure > 90mmHg, despite optimal medical management Known HIV, chronic hepatitis B or chronic hepatitis C infections Women who are pregnant or lactating. Women of childbearing potential must agree to use adequate contraception from time of study entry until at least 3 months after the last administration of study drug. Active clinically serious infection (> grade 2) Thrombotic or embolic events such as cerebral vascular accident including transient ischemic attacks within the last 6 months. Pulmonary hemorrhage/bleeding event ≥ grade 2 within 4 weeks of starting treatment. Any other hemorrhage/bleeding event ≥ grade 3 within 4 weeks of starting treatment Serious non-healing wound, ulcer, or bone fracture Evidence of history of bleeding diathesis or coagulopathy Major surgery, open biopsy, or significant traumatic injury within 4 weeks of starting treatment. Any condition that impairs the ability to swallow whole pills Patients with any type of malabsorption Known or suspected allergy to any of the agents used in this treatment Use of St. John's Wort or rifampin

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Paclitaxel/Carboplatin/Sorafenib<br>Paclitaxel 175 mg/m2 1-3 hour IV infusion, Day 1 Carboplatin AUC 6 infused over 20 minutes IV, Day 1 Sorafenib 400mg PO bid | Drug: Sorafenib<br> <br> * Other names: BAY 43-9006;Drug: Paclitaxel<br>* Paclitaxel<br>Drug: Carboplatin<br>* Carboplatin<br>|
| Active Comparator: Paclitaxel/carboplatin<br>Paclitaxel 175 mg/m2 1-3 hour IV infusion, Day 1 Carboplatin AUC 6 infused over 20 minutes IV | Drug: Paclitaxel<br>* Paclitaxel<br>Drug: Carboplatin<br>* Carboplatin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year Progression-free Survival | The proportion of patients with progression-free survival at 2 years. Progression-free survival is measured from Day 1 of study drug administration to disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death on study. Progression is defined in RECIST v1.1 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 | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Number of patients with either complete response (CR) or partial response (PR) as defined in Response Evaluation Criteria in Solid Tumors (for patients with measurable disease) or determined by CA-125 levels (for patients without measurable disease). Complete Response: Disappearance of all target lesions, disappearance of all non-target lesions, and normalization of CA-125 for at least 4 weeks. In patients who have only elevated CA-125, the CA-125 must normalize (< 23U/mL) for more than 4 weeks. Partial Response: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameters. For patients with elevated CA-125 only, partial response will be defined as a > 50% decrease in the serum CA-125 level. | 18 months | 
| Overall Survival (OS) | Overall survival was measured from the date of study entry until the date of death | 18 months | 
| Toxicity of Paclitaxel/Carboplatin vs. Paclitaxel/Carboplatin/Sorafenib | Number of patients experiencing treatment-related adverse events | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ovarian Cancer