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

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

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.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer
• Intervention / Treatment: Drug: Sorafenib; Drug: Carboplatin; Drug: Paclitaxel

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

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Northeast Arkansas Clinic
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists
    • Ft. Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital
    • St. Petersburg, Florida, United States, 33705
      • Gulfcoast Oncology Associates
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Medical College of Georgia Cancer Specialists
  • Indiana
    • Terre Haute, Indiana, United States, 47802
      • Providence Medical Group
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Center for Cancer and Blood Disorders
    • Bethesda, Maryland, United States, 20817
      • National Capital Clinical Research Consortium
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • St. Joseph Mercy Hospital
    • Grand Rapids, Michigan, United States, 49503
      • Grand Rapids Clinical Oncology Program
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma
  • South Carolina
    • Columbia, South Carolina, United States, 29210
      • South Carolina Oncology Associates, PA
  • Tennessee
    • Chattanooga, Tennessee, United States, 37411
      • Tennessee Valley Clinical Research
    • Collierville, Tennessee, United States, 38017
      • Family Cancer Center
    • Nashville, Tennessee, United States, 37023
      • Tennessee Oncology, PLLC
  • Virginia
    • Newport News, Virginia, United States, 23601
      • Peninsula Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Paclitaxel/Carboplatin/Sorafenib; 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; Other Names: BAY 43-9006; Drug: Carboplatin; Carboplatin; Drug: Paclitaxel; Paclitaxel
Active Comparator: Paclitaxel/carboplatin; Paclitaxel 175 mg/m2 1-3 hour IV infusion, Day 1 Carboplatin AUC 6 infused over 20 minutes IV	Drug: Carboplatin; Carboplatin; Drug: Paclitaxel; Paclitaxel

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: SCRI Development Innovations, LLC
• Collaborators: Bayer

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: October 19, 2006
• First Submitted That Met QC Criteria: October 19, 2006
• First Posted (Estimate): October 20, 2006

Study Record Updates

• Last Update Posted (Estimate): December 22, 2014
• Last Update Submitted That Met QC Criteria: December 12, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Ovarian Cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Carboplatin; Paclitaxel; Sorafenib
• Other Study ID Numbers: SCRI GYN 19; SR05-918