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

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

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.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer
• Intervention / Treatment: Drug: Imatinib Mesylate; Drug: Docetaxel

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 If the toxicity is not resolved to grade 0 or 1 after three weeks, the patient will be withdrawn from the study.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 Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
· 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

Outcome Measure	Time Frame
· 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

Collaborators and Investigators

• Sponsor: Daniela Matei, MD
• Collaborators: Sanofi; Novartis Pharmaceuticals; Walther Cancer Institute
• Investigators: Study Chair: Daniela Matei, M.D., Hoosier Oncology Group, LLC

Publications and helpful links

General Publications

• 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.

Helpful Links

• Hoosier Oncology Group Home Page

Study record dates

Study Major Dates

• Study Start: December 1, 2003
• Primary Completion (ACTUAL): October 1, 2005
• Study Completion (ACTUAL): July 1, 2007

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 14, 2005
• First Posted (ESTIMATE): September 22, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): February 19, 2016
• Last Update Submitted That Met QC Criteria: February 17, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Ovarian Cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protein Kinase Inhibitors; Docetaxel; Imatinib Mesylate
• Other Study ID Numbers: HOG GYN 03-62

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO