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

January 23, 2013 updated by: National Cancer Institute (NCI)

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • San Antonio, Texas, United States, 78229
        • Cancer Therapy and Research Center at The UT Health Science Center at San Antonio

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (paclitaxel, trastuzumab, erlotinib hydrochloride)
See detailed description.
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Drug: paclitaxel
Given IV
Other Names:
  • Taxol
  • Anzatax
  • Asotax
  • TAX
Biological: trastuzumab
Given IV
Other Names:
  • Herceptin
  • anti-c-erB-2
  • MOAB HER2
Drug: erlotinib hydrochloride
Given orally
Other Names:
  • OSI-774
  • erlotinib
  • CP-358,774

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximally tolerated dose (MTD), graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
Time Frame: Up to day 28
Up to day 28
Response rates, as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame: Up to 6 years
Up to 6 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Incidence of adverse events, graded according to the NCI CTC v2.0
Time Frame: Up to 30 days after last study treatment
Up to 30 days after last study treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Muralidhar Beeram, Cancer Therapy and Research Center at The UT Health Science Center at San Antonio

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2002

Primary Completion (Actual)

December 1, 2007

Study Registration Dates

First Submitted

August 5, 2002

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

January 24, 2013

Last Update Submitted That Met QC Criteria

January 23, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02477
  • IDD #01-35
  • U01CA069853 (U.S. NIH Grant/Contract)
  • CDR0000069472 (Registry Identifier: PDQ (Physician Data Query))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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