Neoadjuvant/Adjuvant Chemotherapy, Vaccine & Adjuvant Radiation Therapy in p53-Overexpressing Stage III Breast Cancer

NCT ID: NCT00082641

Last Updated: 2023-09-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-01-01
• Study Completion Date: 2018-01-01

Brief 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.

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

autologous dendritic cell-adenovirus p53 vaccine

Intervention Type: BIOLOGICAL

Given subcutaneously on one of two schedules

Arm II

Patients receive vaccination comprising p53-infected autologous dendritic cells SC at 6, 8, 10, and 12 weeks after completion of radiotherapy.

Group Type: EXPERIMENTAL

autologous dendritic cell-adenovirus p53 vaccine

Intervention Type: BIOLOGICAL

Given subcutaneously on one of two schedules

Interventions

autologous dendritic cell-adenovirus p53 vaccine

Given subcutaneously on one of two schedules

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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
• Female
• ECOG 0-1
• WBC > 4,000/mm^3
• Platelet count > 100,000/mm^3
• Bilirubin < 2 times upper limit of normal (ULN)
• Hepatitis B surface antigen negative
• Hepatitis C antibody negative
• Creatinine < 2 times ULNHIV negative
• Fertile patients must use effective contraception during and for at least 6 months after study participation

Exclusion Criteria

• No prior or concurrent autoimmune disorder
• Not pregnant or nursing/negative pregnancy test
• No other concurrent illness that would preclude study participation
• No prior chemotherapy
• No concurrent participation in another therapeutic clinical trial

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: collaborator

University of Nebraska

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elizabeth C Reed, MD

Role: STUDY_CHAIR

University of Nebraska

Locations

Eppley Cancer Center, University of Nebraska Medical Center

Omaha, Nebraska, United States

Countries

United States

Other Identifiers

CDR0000354507

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-01019

Identifier Type: REGISTRY

Identifier Source: secondary_id

3P30CA036727-20S1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

0371-02-FB

Identifier Type: -

Identifier Source: org_study_id