Imatinib Mesylate and Sunitinib in Treating Patients With Gastrointestinal Stromal Tumors

A Phase I Study of Imatinib Mesylate and SU011248 for Patients With Gastrointestinal Stromal Tumors

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.

Study Overview

• Status: Terminated
• Conditions: Gastrointestinal Stromal Tumor
• Intervention / Treatment: Other: pharmacological study; Drug: sunitinib malate; Drug: imatinib mesylate

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 Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Therapeutic Intervention

Other: pharmacological study; Other Names: Not noted; Drug: sunitinib malate; Other Names: none noted; 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 Names: None noted

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum tolerated dose of imatinib mesylate in combination with sunitinib malate	at 6 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Vanderbilt-Ingram Cancer Center
• Collaborators: 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

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: December 13, 2007
• First Submitted That Met QC Criteria: December 13, 2007
• First Posted (Estimate): December 14, 2007

Study Record Updates

• Last Update Posted (Estimate): November 16, 2011
• Last Update Submitted That Met QC Criteria: November 12, 2011
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Keywords: gastrointestinal stromal tumor
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib; Imatinib Mesylate
• Other Study ID Numbers: VICC GI 0621; P30CA068485 (U.S. NIH Grant/Contract); VU-VICC-GI-0621