Dasatinib as First-Line Therapy in Treating Patients With Gastrointestinal Stromal Tumors

NCT ID: NCT00568750

Last Updated: 2019-06-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-22
• Study Completion Date: 2018-05-16

Brief Summary

RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well dasatinib works as first-line therapy in treating patients with gastrointestinal stromal tumors.

Detailed Description

OBJECTIVES:

Primary

• To determine the efficacy of dasatinib as assessed by fusion PET/CT scan in patients with gastrointestinal stromal tumors.

Secondary

• To determine the efficacy and safety of dasatinib in these patients.
• To correlate the efficacy of dasatinib with KIT and PDGFR mutational status.
• To correlate the efficacy and safety of dasatinib with dasatinib drug exposure.
• To determine the efficacy of second-line treatment with another TK-inhibitor.

OUTLINE: This is a multicenter study.

Patients receive oral dasatinib twice daily on days 1-28. Treatment repeats every 28 days for 26 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for 4 years.

Conditions

Gastrointestinal Stromal Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dasatinib

Group Type: EXPERIMENTAL

dasatinib

Intervention Type: DRUG

Dasatinib is given orally 70 mg BID. Dasatinib will be continued until progression, unacceptable toxicity and up to 2 years (26 cycles, each cycle lasting 4 weeks).

Interventions

dasatinib

Dasatinib is given orally 70 mg BID. Dasatinib will be continued until progression, unacceptable toxicity and up to 2 years (26 cycles, each cycle lasting 4 weeks).

Intervention Type: DRUG

Other Intervention Names

Sprycel

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed gastrointestinal stromal tumor (GIST)
• Measurable disease by conventional scans (CT scan or MRI) within 2 weeks prior to study registration
• Positive PET/CT scan with [^18F]-fluorodeoxyglucose uptake of the target lesions within 2 weeks prior to study registration
• No signs or history of CNS metastases

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• Hemoglobin ≥ 90 g/L (transfusion allowed)
• Neutrophil count ≥ 1.5 x 10^9/L
• Platelet count ≥ 100 x 10^9/L
• Bilirubin ≤ 2 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 2.5 times ULN
• AST and/or ALT ≤ 2.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 12 months after completion of study therapy
• No other malignancy within the past 5 years except for adequately treated carcinoma in situ of the cervix or localized nonmelanoma skin cancer
• No hypocalcemia (i.e., serum calcium ≤ lower limit of normal)
• No clinically significant cardiovascular disease, including any of the following:

• Uncontrolled hypertension
• Congestive heart failure within the past 6 months
• QTc > 450 msec or major conduction abnormality (unless a cardiac pacemaker is present)
• No concurrent medical condition (e.g., active autoimmune disease or uncontrolled diabetes) that would impair the ability of the patient to participate in the study (at the judgment of the investigator) or that may increase the risk of toxicity, including any of the following:

• Pleural or pericardial effusion of any grade
• Clinically significant coagulation or platelet function disorder (e.g., known von Willebrand's disease)
• Infection requiring intravenous antibiotics
• Ongoing significant gastrointestinal bleeding
• Nausea, vomiting, or malabsorption syndrome that could interfere with ingestion or absorption of oral dasatinib
• No known hypersensitivity to study drug

PRIOR CONCURRENT THERAPY:

• No prior therapy for GIST, particularly tyrosine kinase inhibitors at any time
• More than 30 days since prior participation in a clinical trial
• At least 7 days since prior and no concurrent potent CYP3A4 inhibitors, including any of the following:

• Itraconazole, ketoconazole, miconazole, and voriconazole
• Amprenavir, atazanavir, fosamprenavir, indinavir, nelfinavir, and ritonavir
• Ciprofloxacin, clarithromycin, diclofenac, doxycycline, enoxacin, imatinib mesylate, isoniazid, ketamine, nefazodone, nicardipine, propofol, quinidine, and telithromycin
• At least 7 days since prior and no concurrent medications known to prolong the QT interval, including any of the following:

• Quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, and dofetilide
• Erythromycin and clarithromycin
• Chlorpromazine, haloperidol, mesoridazine, thioridazine, and pimozide
• Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, and lidoflazine
• No concurrent IV bisphosphonates during the first 8 weeks of study treatment
• No other concurrent experimental drugs or anticancer therapy
• No concurrent drugs contraindicated for use with dasatinib, according to the dasatinib investigator's brochure

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Montemurro, MD

Role: STUDY_CHAIR

Centre Hospitalier Universitaire Vaudois

Locations

Biomedicum Helsinki

Helsinki, , Finland

Institut Bergonie

Bordeaux, , France

Hopital Edouard Herriot - Lyon

Lyon, , France

Centre Paul Strauss

Strasbourg, , France

Institut Gustave Roussy

Villejuif, , France

Universitaetsklinikum Essen

Essen, , Germany

Kantonsspital Baden

Baden, , Switzerland

Saint Claraspital AG

Basel, , Switzerland

Universitaetsspital-Basel

Basel, , Switzerland

Kantonsspital Bruderholz

Bruderholz, , Switzerland

Kantonsspital Graubuenden

Chur, , Switzerland

Hopital Cantonal Universitaire de Geneve

Geneva, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Kantonsspital Liestal

Liestal, , Switzerland

Kantonsspital - St. Gallen

Sankt Gallen, , Switzerland

Onkozentrum - Klinik im Park

Zurich, , Switzerland

City Hospital Triemli

Zurich, , Switzerland

UniversitaetsSpital Zuerich

Zurich, , Switzerland

Countries

Finland; France; Germany; Switzerland

Other Identifiers

SWS-SAKK-56/07

Identifier Type: -

Identifier Source: secondary_id

EU-20789

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2007-002047-24

Identifier Type: -

Identifier Source: secondary_id

CDR0000577496

Identifier Type: -

Identifier Source: secondary_id

SAKK 56/07

Identifier Type: -

Identifier Source: org_study_id