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

Ovarian Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00390611
• Other study ID #: SCRI GYN 19
• Secondary ID: SR05-918
• Status: Completed
• Phase: Phase 2
• First received: October 19, 2006
• Last updated: December 12, 2014
• Start date: October 2006
• Est. completion date: April 2014

Study information

• Verified date: December 2014
• Source: SCRI Development Innovations, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 85
• Est. completion date: April 2014
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• Sorafenib

• Paclitaxel
Paclitaxel
• Carboplatin
Carboplatin

Locations

Country	Name	City	State
United States	St. Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Medical College of Georgia Cancer Specialists	Augusta	Georgia
United States	Center for Cancer and Blood Disorders	Bethesda	Maryland
United States	National Capital Clinical Research Consortium	Bethesda	Maryland
United States	Tennessee Valley Clinical Research	Chattanooga	Tennessee
United States	Oncology Hematology Care	Cincinnati	Ohio
United States	Family Cancer Center	Collierville	Tennessee
United States	South Carolina Oncology Associates, PA	Columbia	South Carolina
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Holy Cross Hospital	Ft. Lauderdale	Florida
United States	Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan
United States	Northeast Arkansas Clinic	Jonesboro	Arkansas
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Peninsula Cancer Center	Newport News	Virginia
United States	University of Oklahoma	Oklahoma City	Oklahoma
United States	Gulfcoast Oncology Associates	St. Petersburg	Florida
United States	Providence Medical Group	Terre Haute	Indiana

Sponsors (2)

Lead Sponsor	Collaborator
SCRI Development Innovations, LLC	Bayer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	Overall Survival (OS)	Overall survival was measured from the date of study entry until the date of death	18 months	No
Secondary	Toxicity of Paclitaxel/Carboplatin vs. Paclitaxel/Carboplatin/Sorafenib	Number of patients experiencing treatment-related adverse events	18 months	Yes