Vaccine Therapy With Either Neoadjuvant or Adjuvant Chemotherapy and Adjuvant Radiation Therapy in Treating Women With p53-Overexpressing Stage III Breast Cancer
| Status: | Completed |
|---|---|
| Conditions: | Breast Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 19 - 120 |
| Updated: | 2/7/2019 |
| Start Date: | January 2004 |
| End Date: | January 2018 |
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.
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.
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.
- 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.
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
We found this trial at
1
site
985950 Nebraska Medical Center
Omaha, Nebraska 68198
Omaha, Nebraska 68198
402-559-4090
UNMC Eppley Cancer Center at the University of Nebraska Medical Center The Fred & Pamela...
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