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Imatinib Mesylate and Sunitinib in Treating Patients With Gastrointestinal Stromal Tumors
This study is ongoing, but not recruiting participants.
First Received: December 13, 2007   Last Updated: November 17, 2009   History of Changes
Sponsor: Vanderbilt-Ingram Cancer Center
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00573404
  Purpose

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 Intervention Phase
Gastrointestinal Stromal Tumor
Drug: imatinib mesylate
Drug: sunitinib malate
Other: pharmacological study
Phase I

Study Type: Interventional
Study Design: Treatment
Official Title: A Phase I Study of Imatinib Mesylate and SU011248 for Patients With Gastrointestinal Stromal Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose of imatinib mesylate in combination with sunitinib malate [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Toxicity profile as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  • Pharmacokinetics [ Designated as safety issue: No ]
  • Preliminary data on anti-tumor activity of these drugs as assessed by RECIST [ Designated as safety issue: No ]

Estimated Enrollment: 15
Study Start Date: July 2007
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00573404

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
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

Additional Information:
No publications provided

Study ID Numbers: CDR0000579449, VU-VICC-GI-0621
Study First Received: December 13, 2007
Last Updated: November 17, 2009
ClinicalTrials.gov Identifier: NCT00573404     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
gastrointestinal stromal tumor

Additional relevant MeSH terms:
Digestive System Neoplasms
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Gastrointestinal Diseases
Growth Substances
Physiological Effects of Drugs
Enzyme Inhibitors
Angiogenesis Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions
Imatinib
Neoplasms
Neoplasms by Site
Digestive System Diseases
Sunitinib
Therapeutic Uses
Gastrointestinal Neoplasms
Growth Inhibitors
Angiogenesis Modulating Agents
Gastrointestinal Stromal Tumors

ClinicalTrials.gov processed this record on November 27, 2009