Clinical trial NCT00573404: Imatinib Mesylate and Sunitinib in Treating Patients With Gastrointestinal Stromal Tumors
Official title: A Phase I Study of Imatinib Mesylate and SU011248 for Patients With Gastrointestinal Stromal Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Gastrointestinal Stromal Tumor
Keywords: gastrointestinal stromal tumor
Lead sponsor: Vanderbilt-Ingram Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-12-14
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Imatinib mesylate and sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of imatinib mesylate given together with sunitinib in treating patients with gastrointestinal stromal tumors.

Detailed description: OBJECTIVES:

* To determine the maximum tolerated dose of imatinib mesylate in combination with sunitinib malate in patients with gastrointestinal stromal tumors.
* To determine the toxicity of this regimen in these patients.
* To determine the antitumor activity in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of imatinib mesylate.

Patients receive oral sunitinib malate once daily on days 1-14 in course 1 and on days 1-42 in all subsequent courses. Beginning in course 2, patients also receive oral imatinib mesylate once or twice daily on days 1-42. Courses repeat every 6 weeks in the absence of unacceptable toxicity.

Blood samples are collected on day 15 and day 43 for pharmacokinetics.

After completion of study treatment, patients are followed every 6 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Biopsy proven gastrointestinal stromal tumor
* Patients previously treated with imatinib mesylate must have documented progression of disease

  * Untreated disease allowed
* Must have ≥ 1 measurable lesion by RECIST
* No history of or known brain metastases, spinal cord compression,carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease on screening CT or MRI scan

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* ANC ≥ 1,500/μL
* Hemoglobin ≥ 9.0 g/dL
* Platelet count ≥ 150,000/μL
* Total serum bilirubin ≤ 2.0 mg/dL
* Serum calcium ≤ 12.0 mg/dL
* Serum creatinine ≤ 1.8 mg/dL
* AST and ALT ≤ 3 times upper limit of normal (ULN) (5 times ULN if liver function abnormalities are due to underlying malignancy)
* Able to take oral medications
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No grade 3 hemorrhage within the past 4 weeks
* No myocardial infarction, severe or unstable angina, coronary or peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism within the past 6 months
* No ongoing cardiac dysrhythmias ≥ grade 2
* No prolonged QTc interval on baseline EKG
* No hypertension that cannot be controlled by medications (BP \> 150/100 mm Hg, despite medical therapy)
* No pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
* No known HIV or AIDS-related illness or other active infection
* No other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator, preclude study entry
* No malabsorption syndrome
* No prior intolerance of imatinib mesylate or toxicity necessitating dose modification
* No prior intolerance of sunitinib malate or toxicity necessitating dose modification

PRIOR CONCURRENT THERAPY:

* Recovered from all acute toxic effects of prior chemotherapy, radiotherapy, or surgical procedures
* No major surgery or radiotherapy within the past 4 weeks
* No concurrent treatment on another clinical trial, except supportive care trials or non-treatment trials (e.g., quality of life)
* No concurrent ketoconazole and other agents known to induce CYP3A4
* No concurrent theophylline or phenobarbital and/or other agents metabolized by the cytochrome P450 system
* No ongoing therapeutic doses of coumadin, except low-dose oral coumadin up to 2 mg once daily for thrombosis prophylaxis
* No concurrent Hypericum perforatum (St. John's wort) or other herbal medications

Primary outcomes:
measure: Maximum tolerated dose of imatinib mesylate in combination with sunitinib malate
timeFrame: at 6 weeks
Secondary outcomes:
measure: Toxicity profile as assessed by NCI CTCAE v3.0
timeFrame: every 6 weeks
measure: Pharmacokinetics
timeFrame: days 15 & 43
measure: Preliminary data on anti-tumor activity of these drugs as assessed by RECIST
timeFrame: 18 weeks
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center - Cool Springs
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center at Franklin
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Vanderbilt-Ingram Cancer Center
name: Jordan D. Berlin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: OHSU Knight Cancer Institute
name: Charles D. Blanke, MD, FACP
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt-Ingram Cancer Center
name: Emily Chan, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: