Imatinib Mesylate in Combination With Docetaxel for Advanced, Platinum-Refractory Ovarian Cancer - Full Text View

Sponsors and Collaborators:	Hoosier Oncology Group Novartis Sanofi-Aventis Walther Cancer Institute
Information provided by:	Hoosier Oncology Group
ClinicalTrials.gov Identifier:	NCT00216112

Purpose

Imatinib mesylate is an inhibitor of the receptor tyrosine kinases for platelet-derived growth factor (PDGF) and stem cell factor (SCF), c-Kit, and inhibits PDGF- and SCF-mediated cellular events. Docetaxel promotes cell growth arrest by inhibiting the deassembly of tubulin and by promoting at the same time microtubule assembly. Docetaxel has single agent activity in ovarian cancer with response rates of 30-40% in the platinum refractory setting. The combination of imatinib mesylate and docetaxel has potential synergistic effects, based on previous reports showing synergy in-vitro and in-vivo between PDGFR inhibitors or PI3K inhibitors and taxane chemotherapy.

This trial will investigate the efficacy the combination of imatinib mesylate and docetaxel in treating patients with advanced, platinum-refractory ovarian cancer and primary peritoneal carcinomatosis.

Condition	Intervention	Phase
Ovarian Cancer	Drug: Imatinib Mesylate Drug: Docetaxel	Phase II

MedlinePlus related topics: Cancer Ovarian Cancer

Drug Information available for: Docetaxel Imatinib Imatinib mesylate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	Imatinib Mesylate (Gleevec®, STI571) in Combination With Docetaxel (Taxotere) for the Treatment of Advanced, Platinum-Refractory Ovarian Cancer and Primary Peritoneal Carcinomatosis: Hoosier Oncology Group GYN03-62

Further study details as provided by Hoosier Oncology Group:

Primary Outcome Measures:

· To determine response rate (CR, PR and SD) of patients with advanced, platinum-refractory ovarian cancer, whose tumors over-express PDGFR or c-kit receiving imatinib mesylate in combination with docetaxel. [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

· To assess the safety and tolerability of imatinib mesylate in combination with docetaxel in patients with advanced, platinum-refractory ovarian cancer, whose tumors over-express PDGFR or c-kit. [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
· To determine progression free survival and overall survival in patients with advanced, platinum-refractory ovarian cancer, whose tumors over-express PDGFR or c-kit, receiving imatinib mesylate in combination with docetaxel. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
· To determine whether basal level of Akt expression or Akt activation (phospho-Akt) in ovarian tumors impacts response to treatment with imatinib and docetaxel. [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Enrollment:	23
Study Start Date:	December 2003
Study Completion Date:	October 2005

Arms	Assigned Interventions
1: Active Comparator Imatinib + docetaxel	Drug: Imatinib Mesylate Imatinib mesylate 600 mg po qd Drug: Docetaxel Docetaxel 30 mg/m2 (4 of 6 weeks); 1 cycle = 6 weeks

Detailed Description:

OUTLINE: This is a multi-center study.

Submit tumor and serum samples for central review

Imatinib 600 mg (orally qd);
Docetaxel 30mg/m2 (4 of 6 weeks);1 cycle = 6 weeks
Evaluate every other cycle

Each cycle will begin only when the granulocyte count is > 1,500/mm3 and the platelet count is > 100,000/mm3 and any other treatment-related toxicities are < grade 1. If the toxicity is not resolved to grade 0 or 1 after three weeks, the patient will be withdrawn from the study. For days 8, 15, and 22 patients must have an absolute neutrophil count > 1,000/mm3 or greater and platelet count > 75,000/mm3. Imatinib mesylate can be administered if platelets >20,000 and ANC >500.

ECOG performance status 0 or 1

Hematopoietic:·

ANC > 1,500/mm3·
Platelets > 100,000 mm3·
Hgb > 8g/dl

Hepatic:·

Albumin>3gm/dL·
Total bilirubin < ULN·
Maximum Alk Phos: >2.5x but < 5x ULN

Renal:·

Creatinine < 1.5 x ULN·(by Cockroft and Gault)

Cardiovascular:·

No grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months prior to beginning protocol therapy)

Pulmonary:·

Not specified

Eligibility

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

Criteria

Inclusion Criteria:

Histologically documented diagnosis of ovarian cancer, primary peritoneal carcinomatosis or fallopian tube cancer·
Immunohistochemical documentation of c-Kit or PDGFR expression by tumor
At least one measurable site of disease as defined by RECIST or evidence of disease progression by CA125 measurement
Platinum-refractory or platinum-resistant

Exclusion Criteria:

No prior exposure to imatinib (Gleevec®) as single agent or in combination
No chemotherapy within 28 days (42 days for nitrosourea or mitomycin-C) prior to being registered to protocol therapy.
No prior radiotherapy to ³ 25 % of the bone marrow
No known brain metastases.
Negative pregnancy test
No current breastfeeding
No investigational agents within 28 days prior to protocol therapy
No prior malignancy in the past 5 years unless the other primary malignancy is not currently clinically significant, nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ
No severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection)
No known diagnosis of human immunodeficiency virus (HIV) infection.
No major surgery within 28 days prior to being registered to protocol therapy.
No refractory ascites requiring drainage more frequently than once a month
No presence of clinically significant small bowel obstruction
No prior exposure to docetaxel (exposure to paclitaxel is allowed)
No parenteral nutrition within 28 days prior to being registered to protocol therapy.
No concomitant treatment with potent CYP 3A4 inhibitors (i.e., ketoconazole) is permitted during therapy on this protocol.
No therapeutic anticoagulation with warfarin while on study (use of low molecular weight heparin is allowed, if necessary).
No peripheral neuropathy > grade 1
No history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80.
No serious concomitant systemic disorders incompatible with the study
No prior malignancies with the exception of curatively treated basal or squamous carcinoma of the skin, carcinoma in-situ of the cervix, or any other cancer for which the patient has been disease-free for < 5 years.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00216112

Locations

United States, Illinois
Medical & Surgical Specialists, LLC
Galesburg, Illinois, United States, 61401
United States, Indiana
AP&S Clinic
Terre Haute, Indiana, United States, 47804
Center for Cancer Care, Inc., P.C.
New Albany, Indiana, United States, 47150
Elkhart Clinic
Elkhart, Indiana, United States, 46515
Arnett Cancer Care
Lafayette, Indiana, United States, 47904
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202
Medical Consultants, P.C.
Muncie, Indiana, United States, 47303
Oncology Hematology Associates of SW Indiana
Evansville, Indiana, United States, 47714
Fort Wayne Oncology & Hematology, Inc
Fort Wayne, Indiana, United States, 46815

Sponsors and Collaborators

Hoosier Oncology Group

Novartis

Sanofi-Aventis

Walther Cancer Institute

Investigators

Study Chair:

Daniela Matei, M.D.

Hoosier Oncology Group, LLC

More Information

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

Responsible Party:	Hoosier Oncology Group ( Daniela Matei, M.D. )
Study ID Numbers:	HOG GYN 03-62
Study First Received:	September 12, 2005
Last Updated:	April 2, 2008
ClinicalTrials.gov Identifier:	NCT00216112
Health Authority:	United States: Institutional Review Board

Keywords provided by Hoosier Oncology Group:

Ovarian Cancer

Study placed in the following topic categories:

Imatinib
Docetaxel
Genital Diseases, Female
Ovarian cancer
Ovarian Neoplasms
Gonadal Disorders

Genital Neoplasms, Female
Endocrine System Diseases
Urogenital Neoplasms
Endocrinopathy
Ovarian Diseases
Endocrine Gland Neoplasms

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses

Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions
Adnexal Diseases

ClinicalTrials.gov processed this record on January 14, 2009