Sorafenib + Topotecan for Platinum-Resistant Recurrent Ovarian Cancer

NCT ID: NCT00526799

Last Updated: 2016-03-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2010-08-31

Brief Summary

This multi-institutional phase I/II clinical trial will test the tolerability and efficacy of the combination sorafenib and topotecan in patients with recurrent ovarian cancer, which is platinum-resistant (recurrence within 6 months from completing platinum based therapy) or refractory (progressive disease during platinum based therapy).

Detailed Description

OUTLINE: This is a multi-center study.

• Topotecan: 4mg/m2 weekly, 3 weeks on and one week off.
• Sorafenib: Assigned cohort dose for phase I (up to 12 patients) Maximum tolerated dose for phase II (21 total patients)

Cycles will consist of 4 weeks (28 days) with disease evaluations every 8 weeks.

Non-PD and acceptable toxicity: Patients will continue protocol therapy PD or unacceptable toxicity: Patients will discontinue protocol therapy

ECOG performance status 0-1

Life expectancy: Three (3) months

Hematopoietic:

• White blood cell count (WBC) > 3 K/mm3
• Hemoglobin (Hgb) > 9 g/dL
• Platelets > 100 K/mm3
• Absolute neutrophil count (ANC) > 1.5 K/mm3
• INR < 1.5 or a PTT within normal limits. NOTE: Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate.
• No evidence or history of bleeding diathesis or coagulopathy.

Hepatic:

• Bilirubin < 1.5 x ULN
• Aspartate aminotransferase (AST, SGOT) < 2.5 x ULN
• Alanine aminotransferase (ALT, SGPT) < 2.5 x ULN
• Alkaline phosphate < 2.5 x ULN

Renal:

• Creatinine < 1.5 x ULN

Cardiovascular:

• No history of myocardial infarction or angina pectoris or angina equivalent within 6 months prior to registration for protocol therapy (the patient may not be on anti-anginal or anti-arrhythmic medications), or have uncontrolled hypertension or congestive heart failure > class II NYHA

Pulmonary:

• No thrombolic or embolic events such as a cerebrovascular accident, including transient ischemic attacks within the past 6 months.
• No pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 28 days prior to registration for protocol therapy.
• No non-pulmonary hemorrhage/bleeding event > CTCAE Grade 3 within 28 days prior to registration for protocol therapy.

Conditions

Ovarian Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase I

Topotecan 3.5 mg/m\^2 + Sorafenib dose escalation:

Group Type: EXPERIMENTAL

Sorafenib

Intervention Type: DRUG

Phase I: Dose Escalation, Phase II: MTD

Dose level -1: 200mg po daily Dose level 1: 400mg po daily (MTD) Dose level 2: 400mg po bid

Topotecan

Intervention Type: DRUG

3.5mg/m2 weekly, 3 weeks on and one week off.

Phase II

Topotecan 3.5 mg/m\^2 + Sorafenib 400 mg po daily.

Group Type: EXPERIMENTAL

Sorafenib

Intervention Type: DRUG

Phase I: Dose Escalation, Phase II: MTD

Dose level -1: 200mg po daily Dose level 1: 400mg po daily (MTD) Dose level 2: 400mg po bid

Topotecan

Intervention Type: DRUG

3.5mg/m2 weekly, 3 weeks on and one week off.

Interventions

Sorafenib

Phase I: Dose Escalation, Phase II: MTD

Dose level -1: 200mg po daily Dose level 1: 400mg po daily (MTD) Dose level 2: 400mg po bid

Intervention Type: DRUG

Topotecan

3.5mg/m2 weekly, 3 weeks on and one week off.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Have histologically-confirmed epithelial ovarian cancer, primary peritoneal carcinomatosis or fallopian tube cancer. Enrollment of patients with clear cell histology is encouraged.
• Have measurable disease according to RECIST or detectable disease by 1) CA-125 at least twice the ULN within 14 days prior to registration for protocol therapy; 2) Ascites and/or pleural effusion attributed to tumor; 3) solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST definitions for target lesions.
• Have failed at least one prior platinum based chemotherapeutic regimen.
• No more than 3 prior treatment regimens for epithelial ovarian cancer.
• Prior radiation therapy is allowed to < 25% of the bone marrow.
• Be at least 4 weeks since last anti-cancer treatment, radiation or surgery at the time of registration for protocol therapy.
• No active cancer in addition to the epithelial ovarian cancer within the last 5 years, with the exception of: superficial skin cancer (basal cell or squamous cell skin carcinoma; carcinoma in situ of the cervix; Stage I endometrial cancer with less than 50% invasion of the myometrium, or other adequately treated Stage I or II cancer in complete remission.
• Age > 18 years at the time of consent
• Written informed consent and HIPAA authorization for release of personal health information.
• Females of childbearing potential must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 90 days after treatment discontinuation
• Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy.

Exclusion Criteria

• No known or suspected allergy to sorafenib or any agent given in the course of this trial.
• No prior treatment with anti-angiogenesis therapy.
• No active CNS metastases.
• No treatment with any investigational agent within 30 days prior to being registered for protocol therapy.
• No concurrent combination anti-retroviral therapy for the treatment of immunodeficiency.
• No clinically significant infections requiring antibiotic treatment.
• No evidence of bowel obstruction, malabsorption, or other contraindication to oral medication.
• No serious non-healing wound, ulcer, or bone fracture.
• No major surgery, open biopsy or significant traumatic injury within 28 days of registration for protocol therapy.
• No use of St. John's Wort or rifampin (rifampicin) while on protocol therapy.
• No condition that impairs patient's ability to swallow whole pills.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

Hoosier Cancer Research Network

OTHER

Sponsor Role: collaborator

Daniela Matei, MD

OTHER

Sponsor Role: lead

Responsible Party

Daniela Matei, MD

Sponsor-Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Daniela Matei, M.D.

Role: STUDY_CHAIR

Hoosier Oncology Group, Inc.

Locations

Medical & Surgical Specialists, LLC

Galesburg, Illinois, United States

Oncology Hematology Associates of SW Indiana

Evansville, Indiana, United States

Fort Wayne Oncology & Hematology, Inc

Fort Wayne, Indiana, United States

Indiana University Simon Cancer Center

Indianapolis, Indiana, United States

St. Vincent Hospital Cynecologic Oncology

Indianapolis, Indiana, United States

Arnett Cancer Care

Lafayette, Indiana, United States

Medical Consultants, P.C.

Muncie, Indiana, United States

Schwartz Gynecologic Oncology, PLLC

Brightwaters, New York, United States

Countries

United States

References

Matei D, Emerson RE, Schilder J, Menning N, Baldridge LA, Johnson CS, Breen T, McClean J, Stephens D, Whalen C, Sutton G. Imatinib mesylate in combination with docetaxel for the treatment of patients with advanced, platinum-resistant ovarian cancer and primary peritoneal carcinomatosis : a Hoosier Oncology Group trial. Cancer. 2008 Aug 15;113(4):723-32. doi: 10.1002/cncr.23605.

Reference Type: BACKGROUND

PMID: 18618737 (View on PubMed)

Related Links

http://www.hoosiercancer.org

Hoosier Cancer Research Network Homepage

Other Identifiers

GYN06-111

Identifier Type: -

Identifier Source: org_study_id