Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

VX-710, Doxorubicin, and Vincristine in Treating Patients With Recurrent Small Cell Lung Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 18 and over Pharmaceutical / Industry VX-98-710-006 DUMC-1450-98-9, NCI-V99-1537, NCT00003847

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.

Entry 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)

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)

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

Expected Enrollment

A minimum of 35 and a maximum of 92 patients will be accrued for this study.

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.

Gandhi L, Harding MW, Neubauer M, et al.: 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 109 (5): 924-32, 2007.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Vertex Pharmaceuticals, Incorporated

Matthew Harding, PhD, Protocol chair		Ph: 617-577-6401

Registry Information
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)
Trial Start Date		1998-12-15
Registered in ClinicalTrials.gov		NCT00003847
Date Submitted to PDQ		1999-04-02
Information Last Verified		2007-02-26