Clinical trial NCT00216112: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer
Keywords: Ovarian Cancer
Lead sponsor: Hoosier Cancer Research Network
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
name: Sanofi
name: Walther Cancer Institute
First posted: 2005-09-22
Enrollment: 23
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 If the toxicity is not resolved to grade 0 or 1 after three weeks, the patient will be withdrawn from the study.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

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.

Primary outcomes:
measure: · 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.
timeFrame: 24 months
Secondary outcomes:
measure: · 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.
timeFrame: 24 months
measure: · 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.
timeFrame: 24 months
measure: · To determine whether basal level of Akt expression or Akt activation (phospho-Akt) in ovarian tumors impacts response to treatment with imatinib and docetaxel.
timeFrame: 24 months
Other outcomes:
Locations:
city: Galesburg
country: United States
facility: Medical & Surgical Specialists, LLC
state: Illinois
city: Elkhart
country: United States
facility: Elkhart Clinic
state: Indiana
city: Evansville
country: United States
facility: Oncology Hematology Associates of SW Indiana
state: Indiana
city: Fort Wayne
country: United States
facility: Fort Wayne Oncology & Hematology, Inc
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Lafayette
country: United States
facility: Arnett Cancer Care
state: Indiana
city: Muncie
country: United States
facility: Medical Consultants, P.C.
state: Indiana
city: New Albany
country: United States
facility: Center for Cancer Care, Inc., P.C.
state: Indiana
city: Terre Haute
country: United States
facility: AP&S Clinic
state: Indiana
Study officials:
affiliation: Hoosier Oncology Group, LLC
name: Daniela Matei, M.D.
role: STUDY_CHAIR
References:
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.