Clinical trial NCT00568750: Dasatinib as First-Line Therapy in Treating Patients With Gastrointestinal Stromal Tumors
Official title: Dasatinib First-Line Treatment in Gastrointestinal Stromal Tumors. A Multi Center Phase II Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastrointestinal Stromal Tumor
Keywords: gastrointestinal stromal tumor
Lead sponsor: Swiss Group for Clinical Cancer Research
Sponsor class: OTHER
First posted: 2007-12-06
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Response as assessed by fusion PET/CT scan according to EORTC PET Study Group criteria
timeFrame: at 4 weeks compared to baseline
Secondary outcomes:
measure: Best response as assessed by CT scan/MRI
timeFrame: according to RECIST criteria
measure: Best response as assessed by fusion PET/CT scan
timeFrame: at 4 weeks
measure: Clinical benefit
timeFrame: Clinical benefit is defined as CR, PR, or as SD lasting at least 12 weeks, determined according to RECIST
measure: Time to progression
timeFrame: calculated from registration until progression or death due to tumor
measure: Progression-free survival
timeFrame: calculated from registration until progression or death
measure: Time to treatment failure
timeFrame: calculated from registration until premature trial treatment termination due to any reason
measure: Overall survival
timeFrame: Overall survival will be calculated from registration until death or last follow-up, up to 5 years.
measure: Adverse drug reactions according to NCI CTCAE v3.0
timeFrame: Tolerability will be assessed based on the frequency and severity of Adverse Drug Reactions (ADR) coded according to NCI CTCAE v3.0.
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Biomedicum Helsinki
city: Bordeaux
country: France
facility: Institut Bergonie
city: Lyon
country: France
facility: Hopital Edouard Herriot - Lyon
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Basel
country: Switzerland
facility: Saint Claraspital AG
city: Basel
country: Switzerland
facility: Universitaetsspital-Basel
city: Bruderholz
country: Switzerland
facility: Kantonsspital Bruderholz
city: Chur
country: Switzerland
facility: Kantonsspital Graubuenden
city: Geneva
country: Switzerland
facility: Hopital Cantonal Universitaire de Geneve
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Liestal
country: Switzerland
facility: Kantonsspital Liestal
city: St. Gallen
country: Switzerland
facility: Kantonsspital - St. Gallen
city: Zurich
country: Switzerland
facility: Onkozentrum - Klinik im Park
city: Zurich
country: Switzerland
facility: City Hospital Triemli
city: Zurich
country: Switzerland
facility: UniversitaetsSpital Zuerich
Study officials:
affiliation: Centre Hospitalier Universitaire Vaudois
name: Michael Montemurro, MD
role: STUDY_CHAIR
References: