Vaccine Therapy With Either Neoadjuvant or Adjuvant Chemotherapy and Adjuvant Radiation Therapy in Treating Women With p53-Overexpressing Stage III Breast Cancer - Full Text View

Sponsors and Collaborators:	H. Lee Moffitt Cancer Center and Research Institute National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00082641

Purpose

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving vaccine therapy before and/or after chemotherapy and radiation therapy may cause a stronger immune response.

PURPOSE: This randomized phase I/II trial is studying the side effects of two regimens of vaccine therapy and to see how well they work in treating women who are receiving neoadjuvant or adjuvant chemotherapy and adjuvant radiation therapy for stage III breast cancer that overexpresses p53.

Condition	Intervention	Phase
Breast Cancer	Drug: autologous dendritic cell-adenovirus p53 vaccine	Phase I Phase II

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control
Official Title:	1) Adenovirus p53 Infected DC Vaccine For Breast Cancer, 2) Translation of Biotechnology Into the Clinic

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Safety and toxicity [ Designated as safety issue: Yes ]
Immune response [ Designated as safety issue: No ]
Importance of vaccine timing on antigen-specific immune responses [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	January 2004
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental Patients receive vaccination comprising p53-infected autologous dendritic cells subcutaneously (SC) 1 week after completion of doxorubicin and cyclophosphamide, 1 week after completion of paclitaxel (or after surgery for patients with stage III disease), and at 6 and 12 weeks after completion of radiotherapy (for a total of 4 vaccinations).	Drug: autologous dendritic cell-adenovirus p53 vaccine Given subcutaneously on one of two schedules
Arm II: Experimental Patients receive vaccination comprising p53-infected autologous dendritic cells SC at 6, 8, 10, and 12 weeks after completion of radiotherapy.	Drug: autologous dendritic cell-adenovirus p53 vaccine Given subcutaneously on one of two schedules

Detailed Description:

OBJECTIVES:

Determine the safety and toxicity of two different schedules of vaccination comprising p53-infected autologous dendritic cells in women with p53-overexpressing stage III breast cancer undergoing neoadjuvant or adjuvant chemotherapy and adjuvant radiotherapy.
Determine the immune response, in terms of humoral and cellular response, in patients treated with these regimens.
Determine antigen-specific immune responses in patients treated with these regimens.

OUTLINE: This is a randomized, open-label study. Patients are randomized to 1 of 2 treatment arms.

All patients undergo apheresis for the collection of peripheral blood monocytes that are cultured with interleukin-4 and sargramostim (GM-CSF) to produce dendritic cells. The dendritic cells are infected with a recombinant adenoviral vector containing the wild-type p53 gene.

Patients receive doxorubicin IV and cyclophosphamide IV every 2 weeks for 8 weeks (4 courses) followed 2 weeks later by paclitaxel IV every 2 weeks for 8 weeks (4 courses). Patients with stage III disease then undergo surgery. Three weeks after completion of paclitaxel (or after surgery for patients with stage III disease), patients undergo radiotherapy once daily for 6.5 weeks. Patients are then receive vaccine therapy as per the arm to which they were randomized.

Arm I: Patients receive vaccination comprising p53-infected autologous dendritic cells subcutaneously (SC) 1 week after completion of doxorubicin and cyclophosphamide, 1 week after completion of paclitaxel (or after surgery for patients with stage III disease), and at 6 and 12 weeks after completion of radiotherapy (for a total of 4 vaccinations).
Arm II: Patients receive vaccination comprising p53-infected autologous dendritic cells SC at 6, 8, 10, and 12 weeks after completion of radiotherapy.

Treatment in both arms continues in the absence of unacceptable toxicity.

Patients are followed at 1 month, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 20-50 patients (10-25 per treatment arm) will be accrued for this study within 2 years.

Eligibility

Ages Eligible for Study:	19 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed invasive breast cancer meeting the following criteria:
- Clinically locally advanced disease (stage III) with a primary tumor at least 4 cm by mammogram, ultrasound, or palpation AND/OR palpable axillary nodes larger than 1 cm
  - Planned neoadjuvant chemotherapy
p53-overexpressing tumor by immunohistochemistry
Delayed-type hypersensitivity to at least 1 of 3 standard antigens
Hormone receptor status:
- Not specified

PATIENT CHARACTERISTICS:

Age

19 and over

Sex

Female

Menopausal status

Not specified

Performance status

ECOG 0-1

Life expectancy

Not specified

Hematopoietic

WBC > 4,000/mm^3
Platelet count > 100,000/mm^3

Hepatic

Bilirubin < 2 times upper limit of normal (ULN)
Hepatitis B surface antigen negative
Hepatitis C antibody negative

Renal

Creatinine < 2 times ULN

Immunologic

HIV negative
No prior or concurrent autoimmune disorder

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for at least 6 months after study participation
No other concurrent illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

See Disease Characteristics
No prior chemotherapy

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

See Disease Characteristics

Other

No concurrent participation in another therapeutic clinical trial

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00082641

Locations

United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Recruiting
Omaha, Nebraska, United States, 68198-6805
Contact: Clinical Trials Office - UNMC Eppley Cancer Center at the Univ 800-999-5465

Sponsors and Collaborators

H. Lee Moffitt Cancer Center and Research Institute

National Cancer Institute (NCI)

Investigators

Study Chair:

Elizabeth C. Reed, MD

University of Nebraska

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000354507, MCC-UNMC-37102, UNMC-37102
Study First Received:	May 14, 2004
Last Updated:	October 31, 2008
ClinicalTrials.gov Identifier:	NCT00082641
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage IIIA breast cancer
stage IIIB breast cancer

Study placed in the following topic categories:

Skin Diseases
Adenoviridae Infections
Breast Neoplasms
Breast Diseases

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site

ClinicalTrials.gov processed this record on January 15, 2009