Overview

This trial is active, not recruiting.

Condition breast cancer
Treatment autologous dendritic cell-adenovirus p53 vaccine
Phase phase 1/phase 2
Sponsor University of Nebraska
Collaborator National Cancer Institute (NCI)
Start date January 2004
End date December 2014
Trial size 24 participants
Trial identifier NCT00082641, 371-02, CDR0000354507, MCC-UNMC-37102, NCI-2012-01019, UNMC-37102

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(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).
autologous dendritic cell-adenovirus p53 vaccine
Given subcutaneously on one of two schedules
(Experimental)
Patients receive vaccination comprising p53-infected autologous dendritic cells SC at 6, 8, 10, and 12 weeks after completion of radiotherapy.
autologous dendritic cell-adenovirus p53 vaccine
Given subcutaneously on one of two schedules

Primary Outcomes

Measure
Safety and toxicity
time frame: 1 week after each vaccine dose.
Immune response
time frame: Following completion of the 4 vaccines
Importance of vaccine timing on antigen-specific immune responses
time frame: Following completion of the 4 vaccines

Eligibility Criteria

Female participants at least 19 years old.

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

Additional Information

Official title 1) Adenovirus p53 Infected DC Vaccine For Breast Cancer, 2) Translation of Biotechnology Into the Clinic
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.
Trial information was received from ClinicalTrials.gov and was last updated in May 2013.
Information provided to ClinicalTrials.gov by University of Nebraska.