Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Erlotinib, Trastuzumab, and Paclitaxel in Treating Patients With Advanced Solid Tumors

Basic Trial Information

Objectives

1. Determine the safety, quantitative and qualitative toxic effects, maximum tolerated dose, and dose-limiting toxic effects of erlotinib when combined with paclitaxel and trastuzumab (Herceptin) in patients with advanced solid tumors.
2. Determine the relevant pharmacokinetic interactions between these agents in these patients.
3. Determine, preliminarily, the antitumor activity of this regimen in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed metastatic solid tumor for which there are no effective standard treatment options
• HER2 positive (1+ to 3+)
• Tumor has a high likelihood of expressing epidermal growth factor receptor (EGFR)
• No evidence of leptomeningeal disease or brain metastases unless previously treated, currently asymptomatic, and off both antiepileptics and dexamethasone
  • Patients with treated brain metastases are eligible if they are without any clinical change in their brain disease status for at least 4 weeks after whole brain irradiation

Prior/Concurrent Therapy:

Biologic therapy

• No other concurrent immunotherapy
• No concurrent cytokine growth factors (e.g., colony-stimulating factors)

Chemotherapy

• At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered
• No other concurrent chemotherapy

Endocrine therapy

• See Disease Characteristics
• No concurrent hormonal therapy except megestrol as an appetite stimulant or luteinizing hormone-releasing hormone agonists for prostate cancer

Radiotherapy

• See Disease Characteristics
• No concurrent radiotherapy

Surgery

• No prior surgical procedures affecting absorption

Other

• No prior EGFR-targeting therapy
• No other concurrent experimental medications or other specific antitumor therapy
• No concurrent immunosuppressant therapy
• No concurrent antiarrhythmic therapy for a ventricular arrhythmia

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

  OR

• Karnofsky 60-100%

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

Hepatic

• Bilirubin normal
• AST/ALT no greater than 2.5 times upper limit of normal (ULN) (5 times ULN if liver has tumor involvement)

Renal

• Creatinine normal

  OR

• Creatinine clearance at least 60 mL/min

Cardiovascular

• LVEF more than 50% by radionuclide ventriculogram or MUGA scan
• No significant cardiovascular disease
• No prior congestive heart failure requiring therapy
• No unstable angina pectoris
• No myocardial infarction within the past 6 months

Gastrointestinal

• No gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation
  • Patients who are unable to swallow tablets and/or who have silicon-based G-tubes may dissolve the tablets in distilled water
• No active peptic ulcer disease

Other

• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known or suspected hypersensitivity to paclitaxel
• No prior allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib or other study agents
• No concurrent active infection
• No other concurrent medical condition that would preclude study participation
• No persistent grade 2 or greater neurotoxicity/neuropathy from any cause
• No psychiatric disorders or altered mental status that would preclude study participation

Expected Enrollment

A maximum of 40 patients will be accrued for this study within 10-13.3 months.

Outline

This is an open-label, non-randomized, multicenter, dose-escalation study of erlotinib.

• Intermittent schedule: Patients receive paclitaxel IV over 1 hour followed 30 minutes later by trastuzumab (Herceptin) IV over 30 minutes on days 1, 8, and 15 of each course. Patients also receive oral erlotinib once daily on days 3-28 of course 1 and on days 1-28 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

  Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

• Continuous schedule: Once the MTD is determined using the intermittent schedule, an additional 12 patients are accrued to study the tolerability of a continuous schedule comprising paclitaxel and trastuzumab as above on days 1, 8, 15, and 22 and oral erlotinib once daily on days 3-28 during course 1 and on days 1-28 of subsequent courses using the same dose-escalation scheme as above. Courses repeat as above.

Patients are followed every 30 days.

Trial Contact Information

Trial Lead Organizations

Institute for Drug Development

Anthony Tolcher, MD, Protocol chair		Ph: 210-616-5939; 800-340-2872

Registry Information
Official Title		Phase I Study To Determine The Safety, Tolerance And Preliminary Antineoplastic Activity Of Combined EGFR (erbB1) And HER2 (erbB2) Blockade, With OSI-774 And Trastuzumab, In Combination With Weekly Paclitaxel
Trial Start Date		2002-02-01
Trial Completion Date		2007-12-31
Registered in ClinicalTrials.gov		NCT00042809
Date Submitted to PDQ		2002-05-28
Information Last Verified		2008-04-15
NCI Grant/Contract Number		CA69853

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