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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
H. Lee Moffitt Cancer Center and Research Institute
Information provided by (Responsible Party):
Elizabeth Reed, MD, University of Nebraska
ClinicalTrials.gov Identifier:
NCT00082641
First received: May 14, 2004
Last updated: May 14, 2013
Last verified: May 2013
  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
Biological: autologous dendritic cell-adenovirus p53 vaccine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 1) Adenovirus p53 Infected DC Vaccine For Breast Cancer, 2) Translation of Biotechnology Into the Clinic

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • Safety and toxicity [ Time Frame: 1 week after each vaccine dose. ] [ Designated as safety issue: Yes ]
  • Immune response [ Time Frame: Following completion of the 4 vaccines ] [ Designated as safety issue: No ]
  • Importance of vaccine timing on antigen-specific immune responses [ Time Frame: Following completion of the 4 vaccines ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: January 2004
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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
Omaha, Nebraska, United States, 68198-6805
Sponsors and Collaborators
University of Nebraska
H. Lee Moffitt Cancer Center and Research Institute
Investigators
Study Chair: Elizabeth C. Reed, MD University of Nebraska
  More Information

Additional Information:
No publications provided

Responsible Party: Elizabeth Reed, MD, Professor, University of Nebraska
ClinicalTrials.gov Identifier: NCT00082641     History of Changes
Other Study ID Numbers: 371-02, MCC-UNMC-37102, UNMC-37102, CDR0000354507, NCI-2012-01019
Study First Received: May 14, 2004
Last Updated: May 14, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Nebraska:
stage IIIA breast cancer
stage IIIB breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on April 17, 2014