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

1) Adenovirus p53 Infected DC Vaccine For Breast Cancer, 2) Translation of Biotechnology Into the Clinic

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Biological: autologous dendritic cell-adenovirus p53 vaccine

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68198-6805
      • Eppley Cancer Center, University of Nebraska Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Biological: autologous dendritic cell-adenovirus p53 vaccine; Given subcutaneously on one of two schedules
Experimental: Arm II; Patients receive vaccination comprising p53-infected autologous dendritic cells SC at 6, 8, 10, and 12 weeks after completion of radiotherapy.	Biological: autologous dendritic cell-adenovirus p53 vaccine; Given subcutaneously on one of two schedules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced Toxicity to the Vaccine	This outcome measure looks at the safety of the vaccine by documenting the number of grade 2, 3, or toxicities experienced by participants related to the vaccine.	1 week after each vaccine dose.
Percent of Patients With an Immune Response to p53-infected Autologous Dendritic Cells		Through study completion, an average of 18 months
Peak Immune Response as Measured by Number of Spots Per Cells	This outcome measure examined the importance of vaccine timing on antigen-specific relative to the primary cytotoxic therapy on the augmentation of antigen specific immune responses by measuring the duration of immune responses of participants	6 months after last immunization

Collaborators and Investigators

• Sponsor: University of Nebraska
• Collaborators: National Cancer Institute (NCI); H. Lee Moffitt Cancer Center and Research Institute
• Investigators: Study Chair: Elizabeth C Reed, MD, University of Nebraska

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2004
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: May 14, 2004
• First Submitted That Met QC Criteria: May 18, 2004
• First Posted (Estimated): May 19, 2004

Study Record Updates

• Last Update Posted (Actual): September 22, 2023
• Last Update Submitted That Met QC Criteria: September 13, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: stage IIIA breast cancer; stage IIIB breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 0371-02-FB; CDR0000354507 (Registry Identifier: PDQ (Physician Data Query)); NCI-2012-01019 (Registry Identifier: CTRP (Clinical Trials Reporting System)); 3P30CA036727-20S1 (U.S. NIH Grant/Contract)