Phase II Multidose, Single Arm, Multicenter Clinical Trial of Cisplatin and Gemcitabine in Combination With Recombinant Humanized Anti-p185HER2 Monoclonal Antibody (Herceptin) in Patients Who Have Untreated p185HER2 Overexpressing Advanced Local Stage (Stage IIIb Pleural Effusion Only) and Metastatic (Stage IV) Non-Small Cell Lung Cancer
18 Years
N/A
Both
Lung Cancer
Trial Information
Phase II Multidose, Single Arm, Multicenter Clinical Trial of Cisplatin and Gemcitabine in Combination With Recombinant Humanized Anti-p185HER2 Monoclonal Antibody (Herceptin) in Patients Who Have Untreated p185HER2 Overexpressing Advanced Local Stage (Stage IIIb Pleural Effusion Only) and Metastatic (Stage IV) Non-Small Cell Lung Cancer
OBJECTIVES: I. Determine the therapeutic efficacy and toxicity of cisplatin, gemcitabine,
and trastuzumab (Herceptin) in patients with untreated p185-HER2 overexpressing stage IIIB
or IV non-small cell lung cancer. II. Determine the pharmacokinetic interactions among these
drugs in these patients. III. Assess the pharmacodynamics of these drugs in these patients.
OUTLINE: This is a multicenter study. Regimen A: Patients receive gemcitabine IV over 30
minutes followed by cisplatin IV over 2 hours on day 1 and trastuzumab (Herceptin) IV over
90 minutes on day 2. Patients receive trastuzumab IV over 90 minutes followed by gemcitabine
IV over 30 minutes on day 8 and trastuzumab IV over 90 minutes on day 15. Patients proceed
to regimen B on day 22 of regimen A. Regimen B: Patients receive trastuzumab IV over 30-90
minutes, gemcitabine IV over 30 minutes, and cisplatin IV over 2 hours on day 1. Patients
receive trastuzumab IV over 30-90 minutes followed by gemcitabine IV over 30 minutes on day
8 and trastuzumab IV over 30-90 minutes on day 15. Treatment repeats every 21 days for up to
5 courses in the absence of disease progression or unacceptable toxicity. Maintenance: After
completion of 6 courses, patients with stable disease or partial response receive
trastuzumab IV over 30-90 minutes weekly until tumor progression.
PROJECTED ACCRUAL: A total of 20-48 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS: Immunohistochemically confirmed p185-HER2 expressing stage IIIB
(pleural effusions only) or IV non-small cell lung cancer Confirmed overexpression at
least: 1+ p185-HER2 (by DAKO Hercep Test) OR 15 ng/mL serum HER2/neu shed antigen (by
Human HER2 Quantitative ELISA) At least 1 site of measurable disease outside of prior
radiation port Brain metastases allowed provided clinical neurologic status is stable and
head CT scan is stable to improved
PATIENT CHARACTERISTICS: Age: Over 18 Performance status: Zubrod 0-2 Life expectancy: More
than 12 weeks Hematopoietic: WBC at least 3,000/mm3 Absolute neutrophil count at least
1,500/mm3 Platelet count at least 100,000/mm3 Hemoglobin at least 10 g/dL (transfusion
allowed) Hepatic: Bilirubin less than 1.5 mg/dL SGPT no greater than 1.5 times normal
Renal: Creatinine clearance at least 60 mL/min Cardiovascular: No myocardial infarction
within the past 6 months No unstable angina, uncontrolled congestive heart failure, or
uncontrolled arrhythmia Ejection fraction at least 40% Other: No other malignancy within
the past 5 years No concurrent serious infection, including post-obstructive pneumonia No
more than 10% weight loss in past 3 months Not pregnant or nursing Negative pregnancy test
Fertile patients must use adequate contraception
PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior
chemotherapy No other concurrent chemotherapy Endocrine therapy: Not specified
Radiotherapy: See Disease Characteristics At least 3 weeks since prior radiotherapy
(including radiotherapy for brain metastases) No concurrent radiotherapy to only site of
measurable disease Surgery: At least 2 weeks since prior major surgery No concurrent
surgery on only site of measurable disease
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Efficacy of Cisplatin, Gemcitabine, + Trastuzumab in Untreated p185-HER2 Overexpressing Stage IIIB or IV Non-small Cell Lung Cancer
Outcome Time Frame:
21 days cycles for 6 courses
Safety Issue:
No
Principal Investigator
Roy S. Herbst, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
M.D. Anderson Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
DM99-015
NCT ID:
NCT00016367
Start Date:
May 2001
Completion Date:
December 2004
Related Keywords:
- Lung Cancer
- stage IIIB non-small cell lung cancer
- stage IV non-small cell lung cancer
- Carcinoma, Non-Small-Cell Lung
- Lung Neoplasms
Name | Location |
|---|---|
| University of Texas - MD Anderson Cancer Center | Houston, Texas 77030-4009 |
