Trastuzumab and Imatinib Mesylate in Treating Patients With Recurrent or Metastatic HER2/Neu-Expressing Cancer

NCT00084513 | Completed Phase 1

• 4 other identifiers: CDR0000365451P30CA006927FCCC-03041NOVARTIS-FCCC-03041
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth and by stopping blood flow to the tumor. Giving trastuzumab together with imatinib mesylate may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of imatinib mesylate when given together with trastuzumab in treating patients with recurrent or metastatic HER2/neu-expressing (producing) cancer.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specific

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) of imatinib mesylate given concurrently with trastuzumab (Herceptin®) as measured by CTC v 3.0 at course 1

• Response as measured by RECIST criteria every 9 weeks

Secondary Outcomes (2)

• Circulating tumor cells in blood as measured by Immunicom Cell PrepTM at baseline, every 3 weeks until week 9, and then with each disease re-evaluation

• Phosphorylation status of AKT, extracellular signal-regulated kinase (ERK), and KIT as measured by western blot and/or immunohistochemistry at baseline and week 9

Interventions

trastuzumab BIOLOGICAL

imatinib mesylate DRUG

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed cancer that overexpresses HER2/neu, measured 3+ by immunohistochemistry or positive by fluorescence in situ hybridization * Recurrent or metastatic disease * Meets 1 of the following criteria for measurable or evaluable disease: * Unidimensionally measurable disease at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan * Evaluable disease, defined as a lesion on physical examination or imaging study that can be assessed as to changes in size but cannot be clearly measured in 1 dimension (e.g., pleural effusions, ascites, or bone disease) * No carcinomatous meningitis or untreated/uncontrolled metastatic brain parenchymal disease * Prior controlled brain parenchymal disease allowed provided at least 8 weeks since prior therapy AND no symptomatic progression off corticosteroids PATIENT CHARACTERISTICS: Age * 18 and over Performance status * ECOG 0-2 Life expectancy * Not specified Hematopoietic * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 Hepatic * ALT and AST ≤ 2.0 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 2.0 times ULN * Bilirubin ≤ 1.3 mg/dL * No known chronic liver disease (i.e., chronic active hepatitis or cirrhosis) Renal * Creatinine ≤ 2.0 mg/dL Cardiovascular * Ejection fraction ≥ lower limit of normal by MUGA * No uncontrolled or significant cardiovascular disease * No myocardial infarction within the past 6 months * No ischemic heart disease requiring medication * No congestive heart failure Pulmonary * No uncontrolled or significant pulmonary disease Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier contraception during and for 3 months after study participation * No active unresolved infection PRIOR CONCURRENT THERAPY: Biologic therapy * Prior trastuzumab (Herceptin®) allowed * No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) to support blood counts * No other concurrent anticancer biologic agents Chemotherapy * Prior chemotherapy for metastatic disease allowed * At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered * No concurrent anticancer chemotherapy Endocrine therapy * See Disease Characteristics Radiotherapy * At least 4 weeks since prior radiotherapy and recovered Surgery * More than 2 weeks since prior major surgery Other * At least 7 days since prior antibiotics * No concurrent parenteral antibiotics * No other concurrent anticancer agents * No other concurrent investigational drugs * No concurrent therapeutic anticoagulation with warfarin * Concurrent mini-dose warfarin (1 mg/day) for prophylaxis of central venous catheter thrombosis allowed

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

Sponsors & Collaborators

• Fox Chase Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111-2497, United States

Location

MeSH Terms

Interventions

Trastuzumab; Imatinib Mesylate

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Margaret von Mehren, MD

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 10, 2004
• First Posted: June 11, 2004
• Study Start: August 1, 2004
• Study Completion: March 1, 2007
• Last Updated: February 12, 2010

Record last verified: 2010-02

Locations

US (1)