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

Dasatinib First-Line Treatment in Gastrointestinal Stromal Tumors. A Multi Center Phase II Trial

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.

Study Overview

• Status: Completed
• Conditions: Gastrointestinal Stromal Tumor
• Intervention / Treatment: Drug: dasatinib

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.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland, FI-00290
    • Biomedicum Helsinki
• France
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Lyon, France, 69437
    • Hopital Edouard Herriot - Lyon
  • Strasbourg, France, 67065
    • Centre Paul Strauss
  • Villejuif, France, F-94805
    • Institut Gustave Roussy
• Germany
  • Essen, Germany, D-45122
    • Universitaetsklinikum Essen
• Switzerland
  • Baden, Switzerland, CH-5404
    • Kantonsspital Baden
  • Basel, Switzerland, CH-4016
    • Saint Claraspital AG
  • Basel, Switzerland, CH-4031
    • Universitaetsspital-Basel
  • Bruderholz, Switzerland, CH-4101
    • Kantonsspital Bruderholz
  • Chur, Switzerland, CH-7000
    • Kantonsspital Graubuenden
  • Geneva, Switzerland, CH-1211
    • Hôpital Cantonal Universitaire de Genève
  • Lausanne, Switzerland, CH-1011
    • Centre Hospitalier Universitaire Vaudois
  • Liestal, Switzerland, CH-4410
    • Kantonsspital Liestal
  • St. Gallen, Switzerland, CH-9007
    • Kantonsspital - St. Gallen
  • Zurich, Switzerland, CH-8063
    • City Hospital Triemli
  • Zurich, Switzerland, CH-8091
    • Universitaetsspital Zuerich
  • Zurich, Switzerland, 8002
    • Onkozentrum - Klinik im Park

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dasatinib	Drug: 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).; Other Names: Sprycel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response as assessed by fusion PET/CT scan according to EORTC PET Study Group criteria	at 4 weeks compared to baseline

Secondary Outcome Measures

Outcome Measure	Time Frame
Best response as assessed by CT scan/MRI	according to RECIST criteria
Best response as assessed by fusion PET/CT scan	at 4 weeks
Clinical benefit	Clinical benefit is defined as CR, PR, or as SD lasting at least 12 weeks, determined according to RECIST
Time to progression	calculated from registration until progression or death due to tumor
Progression-free survival	calculated from registration until progression or death
Time to treatment failure	calculated from registration until premature trial treatment termination due to any reason
Overall survival	Overall survival will be calculated from registration until death or last follow-up, up to 5 years.
Adverse drug reactions according to NCI CTCAE v3.0	Tolerability will be assessed based on the frequency and severity of Adverse Drug Reactions (ADR) coded according to NCI CTCAE v3.0.

Collaborators and Investigators

• Sponsor: Swiss Group for Clinical Cancer Research
• Investigators: Study Chair: Michael Montemurro, MD, Centre Hospitalier Universitaire Vaudois

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2008
• Primary Completion (Actual): January 18, 2012
• Study Completion (Actual): May 16, 2018

Study Registration Dates

• First Submitted: December 5, 2007
• First Submitted That Met QC Criteria: December 5, 2007
• First Posted (Estimate): December 6, 2007

Study Record Updates

• Last Update Posted (Actual): June 17, 2019
• Last Update Submitted That Met QC Criteria: June 14, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: gastrointestinal stromal tumor
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Dasatinib
• Other Study ID Numbers: SAKK 56/07; SWS-SAKK-56/07; EU-20789; EUDRACT-2007-002047-24; CDR0000577496

Plan for Individual participant data (IPD)

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