Imatinib Mesylate and Sunitinib in Treating Patients With Gastrointestinal Stromal Tumors

NCT00573404 | Terminated Phase 1 DMC

• 3 other identifiers: VICC GI 0621P30CA068485VU-VICC-GI-0621
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 3

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.

Conditions

Gastrointestinal Stromal Tumor

Keywords

gastrointestinal stromal tumor

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of imatinib mesylate in combination with sunitinib malate

  at 6 weeks

Secondary Outcomes (3)

• 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

Study Arms (1)

Therapeutic Intervention

EXPERIMENTAL

Drug: imatinib mesylate; Drug: sunitinib malate; Other: pharmacological study

Interventions

imatinib mesylate 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.

Also known as: None noted

Therapeutic Intervention

sunitinib malate DRUG

Also known as: none noted

Therapeutic Intervention

pharmacological study OTHER

Also known as: Not noted

Therapeutic Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Vanderbilt-Ingram Cancer Center - Cool Springs

Nashville, Tennessee, 37064, United States

Location

Vanderbilt-Ingram Cancer Center at Franklin

Nashville, Tennessee, 37064, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

Imatinib Mesylate; Sunitinib

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Pyrroles; Azoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine; Clinical Director, GI Oncology Program; Director, Phase I Program; Medical Director, Clinical Trials Shared Resources; Medical Oncologist

Study Record Dates

• First Submitted: December 13, 2007
• First Posted: December 14, 2007
• Study Start: July 1, 2007
• Primary Completion: September 1, 2009
• Study Completion: March 1, 2011
• Last Updated: November 16, 2011

Record last verified: 2011-11

Locations

US (3)