Clinical trial NCT00390611: Paclitaxel and Carboplatin With Or Without Sorafenib In The First-Line Treatment Of Patients With Ovarian Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer
Keywords: Ovarian Cancer
Lead sponsor: SCRI Development Innovations, LLC
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2006-10-20
Enrollment: 85
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: 2-year Progression-free Survival
timeFrame: 2 years
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: 18 months
measure: Overall Survival (OS)
timeFrame: 18 months
measure: Toxicity of Paclitaxel/Carboplatin vs. Paclitaxel/Carboplatin/Sorafenib
timeFrame: 18 months
Other outcomes:
Locations:
city: Jonesboro
country: United States
facility: Northeast Arkansas Clinic
state: Arkansas
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Ft. Lauderdale
country: United States
facility: Holy Cross Hospital
state: Florida
city: St. Petersburg
country: United States
facility: Gulfcoast Oncology Associates
state: Florida
city: Augusta
country: United States
facility: Medical College of Georgia Cancer Specialists
state: Georgia
city: Terre Haute
country: United States
facility: Providence Medical Group
state: Indiana
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders
state: Maryland
city: Bethesda
country: United States
facility: National Capital Clinical Research Consortium
state: Maryland
city: Ann Arbor
country: United States
facility: St. Joseph Mercy Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Grand Rapids Clinical Oncology Program
state: Michigan
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Columbia
country: United States
facility: South Carolina Oncology Associates, PA
state: South Carolina
city: Chattanooga
country: United States
facility: Tennessee Valley Clinical Research
state: Tennessee
city: Collierville
country: United States
facility: Family Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Newport News
country: United States
facility: Peninsula Cancer Center
state: Virginia
Study officials:
affiliation: SCRI Development Innovations, LLC
name: John D. Hainsworth, MD
role: PRINCIPAL_INVESTIGATOR
References: