Imatinib Mesylate and Sunitinib in Treating Patients With Gastrointestinal Stromal Tumors

This study has been terminated.
(slow accrual)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jordan Berlin, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier:
NCT00573404
First received: December 13, 2007
Last updated: November 12, 2011
Last verified: November 2011
  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 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: 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 Vanderbilt-Ingram Cancer Center:

Primary Outcome Measures:
  • Maximum tolerated dose of imatinib mesylate in combination with sunitinib malate [ Time Frame: at 6 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Toxicity profile as assessed by NCI CTCAE v3.0 [ Time Frame: every 6 weeks ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics [ Time Frame: days 15 & 43 ] [ Designated as safety issue: No ]
  • Preliminary data on anti-tumor activity of these drugs as assessed by RECIST [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: July 2007
Study Completion Date: March 2011
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

No publications provided

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, VU-VICC-GI-0621
Study First Received: December 13, 2007
Last Updated: November 12, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by 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
Imatinib
Sunitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on August 18, 2014