A Phase II Study of the Safety, Efficacy and Pharmacokinetics of VX-710 in Combination With Doxorubicin and Vincristine in Patients With Small Cell Lung Cancer (SCLC)
18 Years
N/A
Both
Lung Cancer
Trial Information
A Phase II Study of the Safety, Efficacy and Pharmacokinetics of VX-710 in Combination With Doxorubicin and Vincristine in Patients With Small Cell Lung Cancer (SCLC)
OBJECTIVES: I. Establish the safety of VX-710 in combination with doxorubicin and
vincristine in patients with recurrent small cell lung cancer. II. Characterize the plasma
pharmacokinetics of this regimen in these patients. III. Establish the ability of this
regimen to improve the response rate to chemotherapy in these patients who have relapsed on
front line therapy. IV. Evaluate the multidrug resistance profile of these patients in
response to this regimen.
OUTLINE: This is a multicenter study. Stage I: Patients receive VX-710 IV over 72 hours,
followed by doxorubicin IV and vincristine IV four hours after initial VX-710. Vincristine
is administered at half dose in the first 3-6 patients. If no more than 1 of 6 patients
experiences dose limiting toxicity in the half dose cohort, 3 additional patients receive
full dose vincristine. The maximum tolerated dose is defined as the dose preceeding that at
which 2 of 6 patients experience dose limiting toxicity. Stage II: Patients receive VX-710
IV over 72 hours, followed by doxorubicin IV and full dose vincristine IV four hours after
initial VX-710. Treatment continues for up to 6 courses every 3 weeks in the absence of
disease progression or unacceptable toxicity. Patients are followed every 3 months for up to
1 year.
PROJECTED ACCRUAL: A minimum of 35 and a maximum of 92 patients will be accrued for this
study.
Inclusion Criteria
DISEASE CHARACTERISTICS: Histologically confirmed oat cell or intermediate type small cell
lung cancer Patients must have received prior therapy, with the following: Documented
disease progression (new lesions or increased lesion size) after first line therapy No
more than 1 prior chemotherapy regimen Complete or partial response to initial
chemotherapy (must have lasted more than 60 days after end of therapy before relapse
occurred) Bidimensionally measurable disease At least one lesion outside of irradiation
field Pleural effusions are not measurable No brain or bone metastases as only measurable
site No uncontrolled brain or other CNS metastases (surgical excision and/or radiotherapy)
PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy:
Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count
at least 100,000/mm3 Hepatic: AST no greater than 2 times upper limit of normal Bilirubin
no greater than 1.5 mg/dL Renal: Creatinine less than 1.3 mg/dL OR Creatinine clearance
greater than 60 mL/min Cardiovascular: Cardiac ejection fraction greater than 45% by MUGA
or echocardiogram No uncontrolled ventricular arrhythmias Other: Not pregnant or nursing
Negative pregnancy test Fertile patients must use effective contraception No senile
dementia or psychiatric disorders Not concurrent serious infection No major seizure
disorder No grade 3 neuropathies No spinal cord compression No other concurrent unstable
medical condition No other prior malignancies within past 5 years, except: Adequately
treated basal or squamous cell skin cancer Any carcinoma in situ
PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease
Characteristics No prior doxorubicin or vincristine as first line treatment for small cell
lung cancer Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy to
greater than 50% of bone marrow At least 30 days since prior radiotherapy Surgery: Not
specified Other: No concurrent experimental drugs or anticancer therapies Concurrent
medication for chronic medical conditions allowed (e.g., hypertension) No concurrent
cimetidine, phenothiazines, phenobarbital, carbamazepine, trolandeomycin, sulfinpyrazone,
rifampin, Dilantin, and cyclosporine-A (or other P-gp inhibitors)
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Matthew Harding, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
Vertex Pharmaceuticals Incorporated
Authority:
United States: Federal Government
Study ID:
CDR0000067008
NCT ID:
NCT00003847
Start Date:
December 1998
Completion Date:
Related Keywords:
- Lung Cancer
- recurrent small cell lung cancer
- intermediate type small cell lung cancer
- Lung Neoplasms
- Small Cell Lung Carcinoma
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
| Indiana University Cancer Center | Indianapolis, Indiana 46202-5265 |
| Duke Comprehensive Cancer Center | Durham, North Carolina 27710 |
| Fox Chase Cancer Center | Philadelphia, Pennsylvania 19111 |
| Massachusetts General Hospital Cancer Center | Boston, Massachusetts 02114 |
| Dana-Farber Cancer Institute | Boston, Massachusetts 02115 |
| University of Arkansas for Medical Sciences | Little Rock, Arkansas 72205 |
| Fallon Clinic Inc. | Worcester, Massachusetts 01605 |
| St. John's Mercy Medical Center | Saint Louis, Missouri 63141 |
