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

Primary Purpose

Ovarian Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Imatinib Mesylate
Docetaxel
Sponsored by
Daniela Matei, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Cancer focused on measuring Ovarian Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept 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.

Sites / Locations

  • Medical & Surgical Specialists, LLC
  • Elkhart Clinic
  • Oncology Hematology Associates of SW Indiana
  • Fort Wayne Oncology & Hematology, Inc
  • Indiana University Cancer Center
  • Arnett Cancer Care
  • Medical Consultants, P.C.
  • Center for Cancer Care, Inc., P.C.
  • AP&S Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Investigational Treatment

Arm Description

Imatinib Mesylate + Docetaxel

Outcomes

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.

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

Full Information

First Posted
September 12, 2005
Last Updated
February 17, 2016
Sponsor
Daniela Matei, MD
Collaborators
Novartis Pharmaceuticals, Sanofi, Walther Cancer Institute
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1. Study Identification

Unique Protocol Identification Number
NCT00216112
Brief Title
Imatinib Mesylate in Combination With Docetaxel for Advanced, Platinum-Refractory Ovarian Cancer
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 Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
December 2003 (undefined)
Primary Completion Date
October 2005 (Actual)
Study Completion Date
July 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Daniela Matei, MD
Collaborators
Novartis Pharmaceuticals, Sanofi, Walther Cancer Institute

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer
Keywords
Ovarian Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Investigational Treatment
Arm Type
Experimental
Arm Description
Imatinib Mesylate + Docetaxel
Intervention Type
Drug
Intervention Name(s)
Imatinib Mesylate
Intervention Description
Imatinib mesylate 600 mg po qd
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Intervention Description
Docetaxel 30 mg/m2 (4 of 6 weeks); 1 cycle = 6 weeks
Primary Outcome Measure Information:
Title
· 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
Secondary Outcome Measure Information:
Title
· 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
Title
· 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
Title
· 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

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniela Matei, M.D.
Organizational Affiliation
Hoosier Oncology Group, LLC
Official's Role
Study Chair
Facility Information:
Facility Name
Medical & Surgical Specialists, LLC
City
Galesburg
State/Province
Illinois
ZIP/Postal Code
61401
Country
United States
Facility Name
Elkhart Clinic
City
Elkhart
State/Province
Indiana
ZIP/Postal Code
46515
Country
United States
Facility Name
Oncology Hematology Associates of SW Indiana
City
Evansville
State/Province
Indiana
ZIP/Postal Code
47714
Country
United States
Facility Name
Fort Wayne Oncology & Hematology, Inc
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46815
Country
United States
Facility Name
Indiana University Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Arnett Cancer Care
City
Lafayette
State/Province
Indiana
ZIP/Postal Code
47904
Country
United States
Facility Name
Medical Consultants, P.C.
City
Muncie
State/Province
Indiana
ZIP/Postal Code
47303
Country
United States
Facility Name
Center for Cancer Care, Inc., P.C.
City
New Albany
State/Province
Indiana
ZIP/Postal Code
47150
Country
United States
Facility Name
AP&S Clinic
City
Terre Haute
State/Province
Indiana
ZIP/Postal Code
47804
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
18618737
Citation
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.
Results Reference
result
Links:
URL
http://hoosieroncologygroup.org/
Description
Hoosier Oncology Group Home Page

Learn more about this trial

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

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