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

NCT ID: NCT00042809

Last Updated: 2013-01-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-05-31

Brief Summary

Phase I trial to study the effectiveness of combining erlotinib and trastuzumab with paclitaxel in treating patients who have advanced solid tumors. Biological therapies such as erlotinib may interfere with the growth of the tumor cells and slow the growth of the tumor. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining erlotinib and trastuzumab with paclitaxel may kill more tumor cells

Detailed Description

OBJECTIVES:

I. 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.

II. Determine the relevant pharmacokinetic interactions between these agents in these patients.

III. Determine, preliminarily, the antitumor activity of this regimen in these patients.

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.

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

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (paclitaxel, trastuzumab, erlotinib hydrochloride)

See detailed description.

Group Type: EXPERIMENTAL

paclitaxel

Intervention Type: DRUG

Given IV

trastuzumab

Intervention Type: BIOLOGICAL

Given IV

erlotinib hydrochloride

Intervention Type: DRUG

Given orally

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

pharmacological study

Intervention Type: OTHER

Correlative studies

Interventions

paclitaxel

Given IV

Intervention Type: DRUG

trastuzumab

Given IV

Intervention Type: BIOLOGICAL

erlotinib hydrochloride

Given orally

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

pharmacological study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

Anzatax; Asotax; TAX; Taxol; anti-c-erB-2; Herceptin; MOAB HER2; CP-358,774; erlotinib; OSI-774; pharmacological studies

Eligibility Criteria

Inclusion Criteria

• 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
• Performance status - ECOG 0-2
• Performance status - Karnofsky 60-100%
• At least 12 weeks
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Bilirubin normal
• AST/ALT no greater than 2.5 times upper limit of normal (ULN) (5 times ULN if liver has tumor involvement)
• Creatinine normal
• Creatinine clearance at least 60 mL/min
• 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
• 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
• 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
• No other concurrent immunotherapy
• No concurrent cytokine growth factors (e.g., colony-stimulating factors)
• At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered
• No other concurrent chemotherapy
• See Disease Characteristics
• No concurrent hormonal therapy except megestrol as an appetite stimulant or luteinizing hormone-releasing hormone agonists for prostate cancer
• See Disease Characteristics
• No concurrent radiotherapy
• No prior surgical procedures affecting absorption
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Muralidhar Beeram

Role: PRINCIPAL_INVESTIGATOR

Cancer Therapy and Research Center at The UT Health Science Center at San Antonio

Locations

Cancer Therapy and Research Center at The UT Health Science Center at San Antonio

San Antonio, Texas, United States

Countries

United States

Other Identifiers

IDD #01-35

Identifier Type: -

Identifier Source: secondary_id

U01CA069853

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000069472

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02477

Identifier Type: -

Identifier Source: org_study_id