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

Primary Purpose

Lung Cancer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
biricodar dicitrate
doxorubicin hydrochloride
vincristine sulfate
Sponsored by
Vertex Pharmaceuticals Incorporated
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring recurrent small cell lung cancer, intermediate type small cell lung cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • University of Arkansas for Medical Sciences
  • Indiana University Cancer Center
  • Massachusetts General Hospital Cancer Center
  • Dana-Farber Cancer Institute
  • Fallon Clinic Inc.
  • St. John's Mercy Medical Center
  • Roswell Park Cancer Institute
  • Duke Comprehensive Cancer Center
  • Fox Chase Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

Outcomes

Primary Outcome Measures

Response Rate
Analyzed via radiologic imaging according WHO criteria

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
September 4, 2013
Sponsor
Vertex Pharmaceuticals Incorporated
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1. Study Identification

Unique Protocol Identification Number
NCT00003847
Brief Title
VX-710, Doxorubicin, and Vincristine for the Treatment of Patients With Recurrent Small Cell Lung Cancer
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)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2013
Overall Recruitment Status
Terminated
Study Start Date
December 1998 (undefined)
Primary Completion Date
February 2001 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer
Keywords
recurrent small cell lung cancer, intermediate type small cell lung cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
36 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
biricodar dicitrate
Intervention Type
Drug
Intervention Name(s)
doxorubicin hydrochloride
Intervention Type
Drug
Intervention Name(s)
vincristine sulfate
Primary Outcome Measure Information:
Title
Response Rate
Description
Analyzed via radiologic imaging according WHO criteria
Time Frame
Every 2 Cycles

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthew Harding, PhD
Organizational Affiliation
Vertex Pharmaceuticals Incorporated
Official's Role
Study Chair
Facility Information:
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
Indiana University Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202-5265
Country
United States
Facility Name
Massachusetts General Hospital Cancer Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Fallon Clinic Inc.
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01605
Country
United States
Facility Name
St. John's Mercy Medical Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263-0001
Country
United States
Facility Name
Duke Comprehensive Cancer Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
17285598
Citation
Gandhi L, Harding MW, Neubauer M, Langer CJ, Moore M, Ross HJ, Johnson BE, Lynch TJ. A phase II study of the safety and efficacy of the multidrug resistance inhibitor VX-710 combined with doxorubicin and vincristine in patients with recurrent small cell lung cancer. Cancer. 2007 Mar 1;109(5):924-32. doi: 10.1002/cncr.22492.
Results Reference
result

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

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