VX-710, Doxorubicin, and Vincristine for the Treatment of Patients With Recurrent Small Cell Lung Cancer

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT00003847
First received: November 1, 1999
Last updated: September 4, 2013
Last verified: September 2013
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy for the treatment of patients who have recurrent small cell lung cancer following treatment.


Condition Intervention Phase
Lung Cancer
Drug: biricodar dicitrate
Drug: doxorubicin hydrochloride
Drug: vincristine sulfate
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Vertex Pharmaceuticals Incorporated:

Primary Outcome Measures:
  • Response Rate [ Time Frame: Every 2 Cycles ] [ Designated as safety issue: No ]
    Analyzed via radiologic imaging according WHO criteria


Enrollment: 36
Study Start Date: December 1998
Primary Completion Date: February 2001 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Drug: biricodar dicitrate Drug: doxorubicin hydrochloride Drug: vincristine sulfate

Detailed Description:

OBJECTIVES: I. Established the safety of VX-710 in combination with doxorubicin and vincristine for the treatment of patients with recurrent small cell lung cancer. II. Characterized the plasma pharmacokinetics of this regimen in patients. III. Established the ability of this regimen to improve the response rate to chemotherapy in patients who relapsed on front-line therapy. IV. Evaluated the multidrug resistance profile of these patients following this treatment regimen.

OUTLINE: This was a multicenter study. Stage I: Patients received VX-710 IV over 72 hours, followed by doxorubicin IV and vincristine IV four hours after initial VX-710. Vincristine was administered at half dose in the first 3-6 patients. If no more than 1 of 6 patients experienced a dose limiting toxicity in the half dose cohort, 3 additional patients received full dose vincristine. The maximum tolerated dose was defined as the dose preceding that at which 2 of 6 patients experienced a dose limiting toxicity. Stage II: Patients received VX-710 IV over 72 hours, followed by doxorubicin IV and full dose vincristine IV four hours after initial VX-710. Treatment continued for up to 6 courses every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients were followed every 3 months for up to 1 year.

PROJECTED ACCRUAL: A minimum of 35 and a maximum of 92 patients was to be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 front 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, troleandomycin, sulfinpyrazone, rifampin, Dilantin, and cyclosporine-A (or other P-gp inhibitors)

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00003847

Locations
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202-5265
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
Fallon Clinic Inc.
Worcester, Massachusetts, United States, 01605
United States, Missouri
St. John's Mercy Medical Center
Saint Louis, Missouri, United States, 63141
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
Investigators
Study Chair: Matthew Harding, PhD Vertex Pharmaceuticals Incorporated
  More Information

Additional Information:
Publications:
Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT00003847     History of Changes
Other Study ID Numbers: CDR0000067008, VX-98-710-006, DUMC-1450-98-9, NCI-V99-1537
Study First Received: November 1, 1999
Last Updated: September 4, 2013
Health Authority: United States: Federal Government

Keywords provided by Vertex Pharmaceuticals Incorporated:
recurrent small cell lung cancer
intermediate type small cell lung cancer

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Doxorubicin
Vincristine
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on April 20, 2014