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

February 17, 2016 updated by: Daniela Matei, MD

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

Intervention / Treatment

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 If the toxicity is not resolved to grade 0 or 1 after three weeks, the patient will be withdrawn from the study.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

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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.
Time Frame: 24 months
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.
Time Frame: 24 months
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.
Time Frame: 24 months
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.
Time Frame: 24 months
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

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

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HOG GYN 03-62

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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