Comparison of Biological Therapies Following Combination Chemotherapy and Bone Marrow or Peripheral Stem Cell Transplantation in Women With Stage II or Stage III Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00008203
First received: January 6, 2001
Last updated: February 1, 2013
Last verified: May 2003
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Biological therapy may interfere with the growth of the cancer cells. It is not yet known which post-transplant biological therapy regimen is more effective for breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of cyclosporine and interferon gamma to that of interleukin-2 following combination chemotherapy and bone marrow or peripheral stem cell transplantation in women who have stage II or stage III breast cancer.


Condition Intervention Phase
Breast Cancer
Biological: aldesleukin
Biological: recombinant interferon gamma
Drug: carboplatin
Drug: cyclophosphamide
Drug: cyclosporine
Drug: thiotepa
Procedure: autologous bone marrow transplantation
Procedure: peripheral blood stem cell transplantation
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: High-Dose Chemotherapy Followed By Autologous Hematopoietic Stem Cell Support And One Of Two Regimens Aimed At Modifying Immune Reconstitution In Women With High Risk Stage 2 And Stage 3 Breast Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: May 1996
Study Completion Date: May 2008
Primary Completion Date: December 2005 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine the response, disease-free survival (DFS), and overall survival of women with high-risk stage II or III breast cancer treated with high-dose cyclophosphamide, thiotepa, and carboplatin with autologous marrow and/or peripheral blood stem cell transplantation.
  • Determine the safety of immunomodulation consisting of cyclosporine and interferon gamma versus low-dose interleukin-2 in this patient population.
  • Determine parameters associated with immune activation and autologous graft-versus-host disease.
  • Determine which immunomodulation regimen is more efficacious with respect to DSF.

OUTLINE: This is a randomized study. Patients are stratified according to stage (II vs III), age, lymph node status, and inflammatory histology. Patients are randomized to one of two immunomodulation arms.

Autologous harvest of at least 1 million CD34+ cells /kg or 400 million mononuclear cells/kg must be achieved.

All patients receive cyclophosphamide IV continuously and thiotepa IV continuously over 96 hours on days -6 through -3 and carboplatin IV over 5 hours daily on days -6 through -3. Patients undergo autologous bone marrow and/or peripheral blood stem cell transfusion on day 0.

  • Arm I: Patients receive cyclosporine IV over 4 hours twice a day, beginning on day 0 and continuing until discharge from the hospital, and interferon gamma subcutaneously (SC) every 2 days on days 7-28.
  • Arm II: Patients receive interleukin-2 SC daily for 28 days following recovery of blood counts.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year and then annually for 5 years.

PROJECTED ACCRUAL: A total of 70 patients (30 with stage II disease and 40 with stage III disease) will be accrued over 2 years.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed breast cancer

    • Stage II with at least 10 lymph nodes involved with malignancy OR
    • Stage III (any T3b-T4, N2 or N3, M0)
  • Ineligible for other high priority national or institutional study
  • No metastasis to brain (confirmed by CT or MRI)
  • Hormone receptor status:

    • Not specified

PATIENT CHARACTERISTICS:

Age:

  • 18 to physiologic 65

Sex:

  • Female

Menopausal status:

  • Not specified

Performance status:

  • ECOG 0-1

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

Hepatic:

  • Bilirubin less than 2 times normal

Renal:

  • Creatinine less than 1.5 times normal

Cardiovascular:

  • LVEF at least 45%

Other:

  • HIV negative
  • Not pregnant or nursing

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • At least 3 cycles of prior chemotherapy required
  • Stage II patients must have completed 4-6 courses of doxorubicin and/or taxol-based adjuvant chemotherapy
  • Stage III patients must have achieved complete or partial response to 4-6 courses of doxorubicin and/or taxol-based induction chemotherapy
  • No other concurrent chemotherapy

Endocrine therapy:

  • Not specified

Radiotherapy:

  • Not specified

Surgery:

  • Not specified
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00008203

Locations
United States, New York
Herbert Irving Comprehensive Cancer Center
New York, New York, United States, 10032
Sponsors and Collaborators
Herbert Irving Comprehensive Cancer Center
Investigators
Study Chair: Charles S. Hesdorffer, MD Herbert Irving Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Cohen DJ, Vahdat LT, Zipin D, et al.: Randomized trial of low-dose interleukin-2 vs. cyclosporine A and interferon- after high dose chemotherapy with peripheral blood progenitor support in women with high risk primary breast cancer (HRPBC). [Abstract] Breast Cancer Res Treat 88 (1): A-2079, 2004.

ClinicalTrials.gov Identifier: NCT00008203     History of Changes
Other Study ID Numbers: CDR0000068387, CPMC-IRB-7608, CPMC-CAMP-014, NCI-G00-1890
Study First Received: January 6, 2001
Last Updated: February 1, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Interferons
Interferon-gamma
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on September 18, 2014