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

Alternate Title

VX-710 Plus Paclitaxel in Treating Women With Metastatic or Locally Advanced Breast Cancer That Has Not Responded to Paclitaxel

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 18 and over Pharmaceutical / Industry VX-96-710-004 NCI-V97-1200

Objectives

I. Establish the ability of VX-710 and paclitaxel to overcome drug resistance 
in women with metastatic or locally advanced breast cancer who have had 
disease progression with paclitaxel treatment.

II. Establish the safety of VX-710 and paclitaxel used in combination.

III. Establish the plasma pharmacokinetics of paclitaxel when used in 
combination with VX-710.

Entry Criteria

Disease Characteristics:

Histologically proven, unresectable, metastatic or locally advanced breast    
 cancer that is refractory to paclitaxel
 -No CNS metastases

Patients must have bidimensionally measurable disease
  -at least one lesion equal to or greater than 1 x 1 cm

Prior/Concurrent Therapy:

Biologic therapy:
 Prior immunotherapies are allowed

Chemotherapy:
 Prior treatment with paclitaxel is required, and patient must have been      
  refractory within 3 months of study
 Prior therapy with at least one but no more than two chemotherapy
  regimens for advanced diseases
 No prior hypersensitivity to paclitaxel, Cremophor, or any component of
  VX-710
 At least two recent doses of paclitaxel

Endocrine therapy:
 Prior hormonal therapies are allowed

Radiation therapy:
 No prior radiation therapy to more than 33% of bone marrow containing bone
 Must be recovered from prior therapies

Surgery:
 Disease unsuitable for definitive surgical resection

Other:
 No prior bone marrow transplantation
 No prior investigational drug or device within 28 days of study

 No concurrent therapy with the following agents:
 -astemizole             -quercetin
 -cimetidine            -quinidine            
 -cyclosporine          -rifampin  
 -ethinyl estradiol      -tacrolimus
 -ketoconazole          -terfenadine 
 -phenobarital          -troleandomycin   
 -phenytoin                     
 

Patient Characteristics:

Age:
 18 and over

Sex:
 Female

Performance Status:
 ECOG 0-2

Life Expectancy:
 Not specified

Hematopoietic:
 AGC greater than 1,500/mm3
 Platelet count greater than 100,000/mm3

Hepatic:
 SGOT and SGPT less than or equal to 1.5 x ULN
 Bilirubin within the institution's normal limits

Renal:
 Creatinine within the institution's normal limits

Cardiovascular:
 No concurrent uncontrolled ventricular arrhythmias
 No concurrent superior vena cava syndrome
 No myocardial infarction within 6 months
  
Other:
 No psychosis
 No concurrent seizure disorders
 No concurrent spinal cord compression
 No grade 3 neuropathy
 Not pregnant or nursing
  Negative pregnancy test at baseline 
  Effective method of contraception must be used during study
 No prior malignant neoplasms within 5 years, except:
  basal and squamous cell skin cancer
  any in situ cancer
 No concurrent serious illness

Expected Enrollment

19 evaluable patients will be enrolled in the first stage of the study. If one
complete or partial response is achieved enrollment will continue to a total 
of approximately 85 patients.

Outline

This is an open label study.

VX-710 is administered by intravenous infusion over a 24-hour period beginning 
4 hours prior to initiation of paclitaxel treatment. Paclitaxel is 
administered over a 3-hour period. This regimen is repeated every 21 days 
until disease progression, intolerable toxicity, or withdrawal of patient 
consent occurs.

Trial Contact Information

Trial Lead Organizations

Vertex Pharmaceuticals, Incorporated

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