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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00042809
First received: August 5, 2002
Last updated: January 23, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: paclitaxel
Biological: trastuzumab
Drug: erlotinib hydrochloride
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximally tolerated dose (MTD), graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 [ Time Frame: Up to day 28 ] [ Designated as safety issue: Yes ]
  • Response rates, as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of adverse events, graded according to the NCI CTC v2.0 [ Time Frame: Up to 30 days after last study treatment ] [ Designated as safety issue: Yes ]

Enrollment: 40
Study Start Date: May 2002
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (paclitaxel, trastuzumab, erlotinib hydrochloride)
See detailed description.
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Biological: trastuzumab
Given IV
Other Names:
  • anti-c-erB-2
  • Herceptin
  • MOAB HER2
Drug: erlotinib hydrochloride
Given orally
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00042809

Locations
United States, Texas
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Investigators
Principal Investigator: Muralidhar Beeram Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00042809     History of Changes
Other Study ID Numbers: NCI-2012-02477, IDD #01-35, U01CA069853, CDR0000069472
Study First Received: August 5, 2002
Last Updated: January 23, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Paclitaxel
Trastuzumab
Erlotinib
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 16, 2014