Imatinib Mesylate and Sunitinib in Treating Patients With Gastrointestinal Stromal Tumors

NCT ID: NCT00573404

Last Updated: 2011-11-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2011-03-31

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.

Conditions

Gastrointestinal Stromal Tumor

Study Design

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

Study Groups

Therapeutic Intervention

Group Type: EXPERIMENTAL

imatinib mesylate

Intervention Type: DRUG

will start at 200 mg daily and will be escalated up to 400 mg bid.If the 400 mg bid dose is tolerated, no further dose escalation will be performed. In the case of excessive toxicity on the starting dose, the option for de-escalation is provided. Sunitinib will start at 25 mg daily and if tolerated, will be escalated to 37.5 mg daily for subsequent dose levels.

sunitinib malate

Intervention Type: DRUG

pharmacological study

Intervention Type: OTHER

Interventions

imatinib mesylate

will start at 200 mg daily and will be escalated up to 400 mg bid.If the 400 mg bid dose is tolerated, no further dose escalation will be performed. In the case of excessive toxicity on the starting dose, the option for de-escalation is provided. Sunitinib will start at 25 mg daily and if tolerated, will be escalated to 37.5 mg daily for subsequent dose levels.

Intervention Type: DRUG

sunitinib malate

Intervention Type: DRUG

pharmacological study

Intervention Type: OTHER

Other Intervention Names

None noted; none noted; Not noted

Eligibility Criteria

Inclusion 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

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Vanderbilt-Ingram Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Jordan Berlin

Professor of Medicine; Clinical Director, GI Oncology Program; Director, Phase I Program; Medical Director, Clinical Trials Shared Resources; Medical Oncologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jordan D. Berlin, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt-Ingram Cancer Center

Charles D. Blanke, MD, FACP

Role: PRINCIPAL_INVESTIGATOR

OHSU Knight Cancer Institute

Emily Chan, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt-Ingram Cancer Center

Locations

Vanderbilt-Ingram Cancer Center - Cool Springs

Nashville, Tennessee, United States

Vanderbilt-Ingram Cancer Center at Franklin

Nashville, Tennessee, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

P30CA068485

Identifier Type: NIH

Identifier Source: secondary_id

View Link

VU-VICC-GI-0621

Identifier Type: -

Identifier Source: secondary_id

VICC GI 0621

Identifier Type: -

Identifier Source: org_study_id

NCT00495001

Identifier Type: -

Identifier Source: nct_alias