Sorafenib + Topotecan for Platinum-Resistant Recurrent Ovarian Cancer - Full Text View

Sponsor:	Hoosier Oncology Group
Collaborator:	Bayer
Information provided by:	Hoosier Oncology Group
ClinicalTrials.gov Identifier:	NCT00526799

Purpose

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).

Condition	Intervention	Phase
Ovarian Cancer	Biological: Sorafenib Drug: Topotecan	Phase I Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I/II Study of Sorafenib in Combination With Topotecan for the Treatment of Platinum-Resistant Recurrent Ovarian Cancer or Primary Peritoneal Carcinomatosis: Hoosier Oncology Group GYN06-111

Resource links provided by NLM:

MedlinePlus related topics: Cancer Ovarian Cancer

Drug Information available for: Topotecan hydrochloride Topotecan Sorafenib Sorafenib tosylate

U.S. FDA Resources

Further study details as provided by Hoosier Oncology Group:

Primary Outcome Measures:

To find the maximum tolerated dose (MTD) for the phase II component and evaluate the safety and toxicity of the combination Sorafenib plus Topotecan in patients with recurrent or resistant epithelial ovarian cancer. [ Time Frame: Phase I ] [ Designated as safety issue: Yes ]
To assess response in patients with recurrent or resistant epithelial ovarian cancer treated with Sorafenib plus Topotecan. [ Time Frame: Phase II ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine the progression-free survival of patients treated with Sorafenib plus Topotecan. [ Time Frame: Phase II ] [ Designated as safety issue: No ]
To determine the rate of clinical benefit defined as the number of patients experiencing an objective response or a CA125 response [ Time Frame: Phase II ] [ Designated as safety issue: No ]

Enrollment:	30
Study Start Date:	September 2007
Study Completion Date:	August 2010
Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 Topotecan + Sorafenib. Assigned cohort dose for phase I (up to 12 patients); maximum tolerated dose for phase II (21 total patients).	Biological: Sorafenib Dose level -1: 200mg po daily Dose level 1: 400mg po daily Dose level 2: 400mg po bid Dose is escalated until DLT observed. Drug: Topotecan 4mg/m2 weekly, 3 weeks on and one week off.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00526799

Locations

United States, Illinois
Medical & Surgical Specialists, LLC
Galesburg, Illinois, United States, 61401
United States, Indiana
Oncology Hematology Associates of SW Indiana
Evansville, Indiana, United States, 47714
Fort Wayne Oncology & Hematology, Inc
Fort Wayne, Indiana, United States, 46815
Indiana University Simon Cancer Center
Indianapolis, Indiana, United States, 46202
St. Vincent Hospital Cynecologic Oncology
Indianapolis, Indiana, United States, 46260
Arnett Cancer Care
Lafayette, Indiana, United States, 47904
Medical Consultants, P.C.
Muncie, Indiana, United States, 47303
United States, New York
Schwartz Gynecologic Oncology, PLLC
Brightwaters, New York, United States, 11718

Sponsors and Collaborators

Hoosier Oncology Group

Bayer

Investigators

Study Chair:

Daniela Matei, M.D.

Hoosier Oncology Group, Inc.

More Information

Additional Information:

Hoosier Oncology Group Home Page This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Daniela Matei, M.D., Hoosier Oncology Group
ClinicalTrials.gov Identifier:	NCT00526799 History of Changes
Other Study ID Numbers:	GYN06-111
Study First Received:	September 5, 2007
Last Updated:	April 28, 2011
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:

Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders

Topotecan
Sorafenib
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012