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

Alternate Title

Gene Therapy Plus Chemotherapy in Treating Patients With Breast Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	Over 18	NCI	FCCC-97009 NCI-T97-0042, NCT00004038, T97-0042

Objectives

I.  Determine the effect of adenovirus p53 (Ad-p53) on chemotherapy-induced 
apoptosis in lesions in patients with breast cancer.

II.  Determine p53 protein expression following intralesional injections of 
Ad-p53 by immunohistochemistry and reverse transcriptase polymerase chain 
reaction in this patient population.

III.  Determine the time course and magnitude of the development of a humoral 
antibody response to the adenoviral vector in this patient population.

IV.  Determine the ability of transfected p53 to upregulate downstream signals 
important in G1 arrest by assaying for WAF1 mRNA and apoptosis in this patient 
population.

V.  Determine the toxicities and side effects of intralesional injections of 
Ad-p53 given in combination with standard chemotherapy in patients with 
cutaneous and subcutaneous metastatic breast cancer amenable to injections and 
biopsies.

VI.  Determine if there is an increase in apoptosis induced by Ad-53 compared 
to baseline in this patient population.

Entry Criteria

Disease Characteristics:

Histologically confirmed epithelial breast cancer

At least 3 cutaneous or subcutaneous lesions required

Measurable disease that includes, but is not limited to, cutaneous or
subcutaneous metastases

Hormone receptor status:
 Not specified

Prior/Concurrent Therapy:

Biologic therapy:
 Not specified

Chemotherapy:
 Concurrent cytotoxic chemotherapy allowed, if stable and responding
 At least 4 weeks since prior chemotherapy, if starting a new regimen
 
Endocrine therapy:
 Not specified

Radiotherapy:
 At least 4 weeks since radiotherapy
 Prior adjuvant radiotherapy to the chest wall allowed
 At least 6 months since radiotherapy to lesions that are to be injected
 
Surgery:
 Not specified


Other:
 Recovered from prior therapy

Patient Characteristics:

Age:
 Over 18

Menopausal status:
 Not specified

Performance status:
 ECOG 0-2

Life expectancy:
 Not specified

Hematopoietic:
 Absolute granulocyte count at least 1,500/mm3
 Hemoglobin greater than 8 g/dL
 Platelet count greater than 100,000/mm3
 
Hepatic:
 Bilirubin less than 2 mg/dL
 PT/PTT within normal range
 SGOT/SGPT less than 2 times upper limit of normal
  
Renal:
 Creatinine less than 1.8 mg/dL

Other:
 Not pregnant
 Fertile patients must use effective contraception during and for 3 months
  after therapy

Expected Enrollment

Approximately 12-20 patients will be accrued for this study within 12-24 months.

Outline

Patients undergo biopsy of one of their skin nodules prior to any treatment.  
Patients receive the Ad-p53 gene therapy in one nodule and injection of a 
second nodule with Dulbecco's phosphate buffered saline.  The next day, 
patients begin chemotherapy, which may be given weekly and continues every 
21-28 days for up to 6 courses.  On day 3, patients return for biopsy of 
injected nodules.  Biopsies are only performed during the first course.  
Patients may receive further injections of the Ad-p53 gene with subsequent 
courses of chemotherapy, for up to six courses.

Patients are followed monthly for 4 months.

Trial Contact Information

Trial Lead Organizations

Fox Chase Cancer Center - Philadelphia

Margaret von Mehren, MD, Protocol chair		Ph: 215-728-3545; 888-369-2427

Registry Information
Official Title		Pilot Study of p53 Intralesional Gene Therapy With Chemotherapy in Breast Cancer
Trial Start Date		1999-01-11
Registered in ClinicalTrials.gov		NCT00004038
Date Submitted to PDQ		1998-07-30
Information Last Verified		2001-06-01
NCI Grant/Contract Number		P30-CA06927, R01-CA5262