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

Sponsor

Daniela Matei, MD (Other)

Overall Status

Completed

CT.gov ID

NCT00216112

Collaborator

Novartis Pharmaceuticals (Industry), Sanofi (Industry), Walther Cancer Institute (Other)

Enrollment

Locations

Arm

Duration (Months)

2.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Ovarian Cancer	Drug: Imatinib Mesylate Drug: Docetaxel	Phase 2

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 If the toxicity is not resolved to grade 0 or 1 after three weeks, the patient will be withdrawn from the study.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

Study Design

Study Type:

Interventional

Actual Enrollment :

23 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Dec 1, 2003

Actual Primary Completion Date :

Oct 1, 2005

Actual Study Completion Date :

Jul 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Investigational Treatment Imatinib Mesylate + Docetaxel	Drug: Imatinib Mesylate Imatinib mesylate 600 mg po qd Drug: Docetaxel Docetaxel 30 mg/m2 (4 of 6 weeks); 1 cycle = 6 weeks

Arm

Intervention/Treatment

Experimental: Investigational Treatment

Imatinib Mesylate + Docetaxel

Drug: Imatinib Mesylate

Imatinib mesylate 600 mg po qd

Drug: Docetaxel

Docetaxel 30 mg/m2 (4 of 6 weeks); 1 cycle = 6 weeks

Outcome Measures

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. [24 months]

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. [24 months]
· 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. [24 months]
· To determine whether basal level of Akt expression or Akt activation (phospho-Akt) in ovarian tumors impacts response to treatment with imatinib and docetaxel. [24 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Medical & Surgical Specialists, LLC	Galesburg	Illinois	United States	61401
2	Elkhart Clinic	Elkhart	Indiana	United States	46515
3	Oncology Hematology Associates of SW Indiana	Evansville	Indiana	United States	47714
4	Fort Wayne Oncology & Hematology, Inc	Fort Wayne	Indiana	United States	46815
5	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202
6	Arnett Cancer Care	Lafayette	Indiana	United States	47904
7	Medical Consultants, P.C.	Muncie	Indiana	United States	47303
8	Center for Cancer Care, Inc., P.C.	New Albany	Indiana	United States	47150
9	AP&S Clinic	Terre Haute	Indiana	United States	47804