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

National Cancer Institute (NCI)

Status and phase

Completed

Phase 1

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Treatments

Other: laboratory biomarker analysis

Biological: trastuzumab

Drug: erlotinib hydrochloride

Drug: paclitaxel

Other: pharmacological study

Study type

Interventional

Funder types

NIH

Identifiers

NCT00042809

IDD #01-35

NCI-2012-02477

U01CA069853 (U.S. NIH Grant/Contract)

CDR0000069472 (Registry Identifier)

Details and patient eligibility

About

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

Full 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.

Enrollment

40 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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