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

Phase 2
Completed
Conditions
Ovarian Cancer
Interventions
Registration Number
NCT00390611
Lead Sponsor
SCRI Development Innovations, LLC
Brief Summary

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

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

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
85
Inclusion Criteria
  1. Histologically confirmed, stage III or IV epithelial ovarian carcinoma

  2. No previous treatment with chemotherapy or radiation therapy

  3. All patients must have undergone cytoreductive surgery, with the

    following results:

    1. No residual tumor nodule > 3cm

    2. No residual tumor involvement of the bowel (ie. invasion into bowel

      wall)

    3. No residual intestinal obstruction

  4. Measurable or evaluable disease. Patients with elevated CA-125 levels

    and/or evaluable disease per RECIST criteria are eligible.

  5. ECOG performance status 0 or 1.

  6. ANC ≥ 1500/µL, platelets ≥ 100,000/µL, hemoglobin ≥ 9.0 g/dL.

  7. 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)

  8. Serum creatinine _ 1.5 x ULN

  9. 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.

  10. Women of childbearing potential must have a negative serum pregnancy

    test performed within 7 days prior to start of treatment.

  11. Patients must be able to understand the nature of this study and give

written informed consent.

Exclusion Criteria
  1. Age < 18 years

  2. 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

  3. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy

  4. Patients with CNS metastases. Patients with neurological symptoms

    must undergo a CT scan/MRI of the brain to exclude brain metastasis.

  5. Uncontrolled hypertension defined as systolic blood pressure > 150mmHg or diastolic pressure > 90mmHg, despite optimal medical management

  6. Known HIV, chronic hepatitis B or chronic hepatitis C infections

  7. 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.

  8. Active clinically serious infection (> grade 2)

  9. Thrombotic or embolic events such as cerebral vascular accident

    including transient ischemic attacks within the last 6 months.

  10. Pulmonary hemorrhage/bleeding event ≥ grade 2 within 4 weeks of

    starting treatment.

  11. Any other hemorrhage/bleeding event ≥ grade 3 within 4 weeks of

    starting treatment

  12. Serious non-healing wound, ulcer, or bone fracture

  13. Evidence of history of bleeding diathesis or coagulopathy

  14. Major surgery, open biopsy, or significant traumatic injury within 4 weeks

    of starting treatment.

  15. Any condition that impairs the ability to swallow whole pills

  16. Patients with any type of malabsorption

  17. Known or suspected allergy to any of the agents used in this treatment

  18. Use of St. John's Wort or rifampin

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Paclitaxel/carboplatinCarboplatinPaclitaxel 175 mg/m2 1-3 hour IV infusion, Day 1 Carboplatin AUC 6 infused over 20 minutes IV
Paclitaxel/Carboplatin/SorafenibSorafenibPaclitaxel 175 mg/m2 1-3 hour IV infusion, Day 1 Carboplatin AUC 6 infused over 20 minutes IV, Day 1 Sorafenib 400mg PO bid
Paclitaxel/Carboplatin/SorafenibPaclitaxelPaclitaxel 175 mg/m2 1-3 hour IV infusion, Day 1 Carboplatin AUC 6 infused over 20 minutes IV, Day 1 Sorafenib 400mg PO bid
Paclitaxel/Carboplatin/SorafenibCarboplatinPaclitaxel 175 mg/m2 1-3 hour IV infusion, Day 1 Carboplatin AUC 6 infused over 20 minutes IV, Day 1 Sorafenib 400mg PO bid
Paclitaxel/carboplatinPaclitaxelPaclitaxel 175 mg/m2 1-3 hour IV infusion, Day 1 Carboplatin AUC 6 infused over 20 minutes IV
Primary Outcome Measures
NameTimeMethod
2-year Progression-free Survival2 years

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

Secondary Outcome Measures
NameTimeMethod
Overall Survival (OS)18 months

Overall survival was measured from the date of study entry until the date of death

Toxicity of Paclitaxel/Carboplatin vs. Paclitaxel/Carboplatin/Sorafenib18 months

Number of patients experiencing treatment-related adverse events

Overall Response Rate (ORR)18 months

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.

Trial Locations

Locations (17)

Northeast Arkansas Clinic

🇺🇸

Jonesboro, Arkansas, United States

Florida Cancer Specialists

🇺🇸

Fort Myers, Florida, United States

Holy Cross Hospital

🇺🇸

Ft. Lauderdale, Florida, United States

Medical College of Georgia Cancer Specialists

🇺🇸

Augusta, Georgia, United States

Gulfcoast Oncology Associates

🇺🇸

St. Petersburg, Florida, United States

Providence Medical Group

🇺🇸

Terre Haute, Indiana, United States

St. Joseph Mercy Hospital

🇺🇸

Ann Arbor, Michigan, United States

Grand Rapids Clinical Oncology Program

🇺🇸

Grand Rapids, Michigan, United States

South Carolina Oncology Associates, PA

🇺🇸

Columbia, South Carolina, United States

Tennessee Valley Clinical Research

🇺🇸

Chattanooga, Tennessee, United States

Family Cancer Center

🇺🇸

Collierville, Tennessee, United States

Peninsula Cancer Center

🇺🇸

Newport News, Virginia, United States

Oncology Hematology Care

🇺🇸

Cincinnati, Ohio, United States

University of Oklahoma

🇺🇸

Oklahoma City, Oklahoma, United States

Tennessee Oncology, PLLC

🇺🇸

Nashville, Tennessee, United States

Center for Cancer and Blood Disorders

🇺🇸

Bethesda, Maryland, United States

National Capital Clinical Research Consortium

🇺🇸

Bethesda, Maryland, United States

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