Imatinib Mesylate and Sunitinib in Treating Patients With Gastrointestinal Stromal Tumors

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Gastrointestinal Stromal Tumor	Drug: imatinib mesylate; Drug: sunitinib malate; Other: pharmacological study	Phase 1

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	6 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase I Study of Imatinib Mesylate and SU011248 for Patients With Gastrointestinal Stromal Tumors
Study Start Date :	July 2007
Actual Primary Completion Date :	September 2009
Actual Study Completion Date :	March 2011

Arms and Interventions

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Arm

Intervention/treatment

Experimental: Therapeutic Intervention

Drug: 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.; Other Name: None noted Drug: sunitinib malate; Not specified; Other Name: none noted Other: pharmacological study; Not specified; Other Name: Not noted

Outcome Measures

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Primary Outcome Measures :

1. Maximum tolerated dose of imatinib mesylate in combination with sunitinib malate [ Time Frame: at 6 weeks ]

Secondary Outcome Measures :

1. Toxicity profile as assessed by NCI CTCAE v3.0 [ Time Frame: every 6 weeks ]
2. Pharmacokinetics [ Time Frame: days 15 & 43 ]
3. Preliminary data on anti-tumor activity of these drugs as assessed by RECIST [ Time Frame: 18 weeks ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Locations

United States, Tennessee
Vanderbilt-Ingram Cancer Center - Cool Springs
Nashville, Tennessee, United States, 37064
Vanderbilt-Ingram Cancer Center at Franklin
Nashville, Tennessee, United States, 37064
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838

Sponsors and Collaborators

Vanderbilt-Ingram Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:	Jordan D. Berlin, MD	Vanderbilt-Ingram Cancer Center
Principal Investigator:	Charles D. Blanke, MD, FACP	OHSU Knight Cancer Institute
Principal Investigator:	Emily Chan, MD, PhD	Vanderbilt-Ingram Cancer Center

More Information

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Responsible Party:	Jordan Berlin, Professor of Medicine; Clinical Director, GI Oncology Program; Director, Phase I Program; Medical Director, Clinical Trials Shared Resources; Medical Oncologist, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier:	NCT00573404 History of Changes
Obsolete Identifiers:	NCT00495001
Other Study ID Numbers:	VICC GI 0621; P30CA068485 ( U.S. NIH Grant/Contract ); VU-VICC-GI-0621
First Posted:	December 14, 2007
Last Update Posted:	November 16, 2011
Last Verified:	November 2011

Keywords provided by Jordan Berlin, Vanderbilt-Ingram Cancer Center:

gastrointestinal stromal tumor

Additional relevant MeSH terms:

Gastrointestinal Stromal Tumors; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Sunitinib	Imatinib Mesylate; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors