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

Gastrointestinal Stromal Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00568750
• Other study ID #: SAKK 56/07
• Secondary ID: SWS-SAKK-56/07EU
• Status: Completed
• Phase: Phase 2
• Start date: January 22, 2008
• Est. completion date: May 16, 2018

Study information

• Verified date: January 2019
• Source: Swiss Group for Clinical Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: May 16, 2018
• Est. primary completion date: January 18, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Gastrointestinal Stromal Tumor
• Gastrointestinal Stromal Tumors

Intervention

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).

Locations

Country	Name	City	State
Finland	Biomedicum Helsinki	Helsinki
France	Institut Bergonie	Bordeaux
France	Hopital Edouard Herriot - Lyon	Lyon
France	Centre Paul Strauss	Strasbourg
France	Institut Gustave Roussy	Villejuif
Germany	Universitaetsklinikum Essen	Essen
Switzerland	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	St. Gallen
Switzerland	City Hospital Triemli	Zurich
Switzerland	Onkozentrum - Klinik im Park	Zurich
Switzerland	UniversitaetsSpital Zuerich	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
Swiss Group for Clinical Cancer Research

Countries where clinical trial is conducted

Finland,  France,  Germany,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response as assessed by fusion PET/CT scan according to EORTC PET Study Group criteria		at 4 weeks compared to baseline
Secondary	Best response as assessed by CT scan/MRI		according to RECIST criteria
Secondary	Best response as assessed by fusion PET/CT scan		at 4 weeks
Secondary	Clinical benefit		Clinical benefit is defined as CR, PR, or as SD lasting at least 12 weeks, determined according to RECIST
Secondary	Time to progression		calculated from registration until progression or death due to tumor
Secondary	Progression-free survival		calculated from registration until progression or death
Secondary	Time to treatment failure		calculated from registration until premature trial treatment termination due to any reason
Secondary	Overall survival		Overall survival will be calculated from registration until death or last follow-up, up to 5 years.
Secondary	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.