Phase III Comparison of Adjuvant Chemotherapy W/High-Dose Cyclophosphamide Plus Doxorubicin (AC) vs Sequential Doxorubicin Fol by Cyclophosphamide (A-C) in High Risk Breast Cancer Patients With 0-3 Positive Nodes (Intergroup, CALGB 9394)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Cancer and Leukemia Group B
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00590785
First received: December 26, 2007
Last updated: November 21, 2013
Last verified: November 2013
  Purpose

To compare disease-free survival (DFS), overall survival (s), and toxicity of high-isk primary breast cancer patients with negative axillary lymph nodes or with one to three positive nodes treated with adjuvant high-dose chemotherapy with doxorubicin plus cyclophosphamide (AC), versus high-dose sequential chemotherapy with doxorubicin followed by cyclophosphamide (A-->C).


Condition Intervention Phase
High Risk
Breast Cancer
Positive Nodes
Cyclophosphamide
Doxorubicin
Drug: Doxorubicin
Drug: Cyclophosphamide
Drug: G-CSF
Drug: tamoxifen
Drug: ciprofloxacin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Comparison of Adjuvant Chemotherapy W/High-Dose Cyclophosphamide Plus Doxorubicin (AC) vs Sequential Doxorubicin Fol by Cyclophosphamide (A-C) in High Risk Breast Cancer Patients With 0-3 Positive Nodes (Intergroup, CALGB 9394)

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • To compare disease-free survival (DFS), overall survival (s), and toxicity of high-isk primary breast cancer patients with negative axillary lymph nodes or with one to three positive nodes. [ Time Frame: Conclusion of the study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To obtain tumor tissue for biologic studies. The details of these biologic studies will be described in a companion protocol or protocols to be developed through the Intergroup mechanism. [ Time Frame: Conclusion of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: August 1996
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Doxorubicin
High-dose doxorubicin + cyclophosphamide (AC) x 6 cycles with G-CSF on Days 3 - 12 and followed in postmenopausal patients and hormone receptor-positive premenopausal patients by tamoxifen 20 mg daily for 5 years.
Drug: Cyclophosphamide
High-dose doxorubicin + cyclophosphamide (AC) x 6 cycles with G-CSF on Days 3 - 12 and followed in postmenopausal patients and hormone receptor-positive premenopausal patients by tamoxifen 20 mg daily for 5 years.
Drug: G-CSF
High-dose doxorubicin + cyclophosphamide (AC) x 6 cycles with G-CSF on Days 3 - 12 and followed in postmenopausal patients and hormone receptor-positive premenopausal patients by tamoxifen 20 mg daily for 5 years.
Other Name: Filgrastim
Drug: tamoxifen
High-dose doxorubicin + cyclophosphamide (AC) x 6 cycles with G-CSF on Days 3 - 12 and followed in postmenopausal patients and hormone receptor-positive premenopausal patients by tamoxifen 20 mg daily for 5 years.
Experimental: 2 Drug: Doxorubicin
High-dose doxorubicin + cyclophosphamide (AC) x 6 cycles with G-CSF on Days 3 - 12 and followed in postmenopausal patients and hormone receptor-positive premenopausal patients by tamoxifen 20 mg daily for 5 years.
Drug: Cyclophosphamide
High-dose doxorubicin + cyclophosphamide (AC) x 6 cycles with G-CSF on Days 3 - 12 and followed in postmenopausal patients and hormone receptor-positive premenopausal patients by tamoxifen 20 mg daily for 5 years.
Drug: G-CSF
High-dose doxorubicin + cyclophosphamide (AC) x 6 cycles with G-CSF on Days 3 - 12 and followed in postmenopausal patients and hormone receptor-positive premenopausal patients by tamoxifen 20 mg daily for 5 years.
Other Name: Filgrastim
Drug: ciprofloxacin
High-dose sequential doxorubicin x 4 given with G-CSF on Days 3 - 12+ and followed by high-dose cyclophosphamide x 3 (A+C) given with G-CSF and ciprofloxacin on Days 3-12, followed in postmenopausal patients and hormone receptor-positive premenopausal patients by tamxifen 20 mg daily for 5 years.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria
  • Patients must have been diagnosed with primary invasive adenocarcinoma of the breast. Those patients with the special types including pure tubular, mucinous and papillary carcinoma are not eligible. Patients must not have sarcoma, lymphoma, or apocrine, adenocystic or squamous cell cancer of the breast. Patients must not have recurrent invasive breast cancer. Metaplastic carcinomas are eligible as a variant form of adenocarcinoma.
  • Patients must have undergone an axillary dissection, and at least 6 nodes must have een removed and examined. Nodal involvement by tumor must be negative or must not xceed three positive nodes.
  • disease must be considered sufficiently high-risk by the investigator to justify the use of chemotherapy. To be eligible, disease must satisfy one of the following requirements:

    1. Tumor is both ER negative and PgR negative and greater than 1.0 cm in greatest diameter. Negative is defined as c 10 fmollmg cytosol protein if measured in these units; othennrise negative is defined according to institutional standards.
    2. Tumor that is greater than 2.0 cm in greatest diameter irrespective of hormone receptor status (including unknown).
    3. Tumor involves one to three axillary lymph nodes.
  • Breast cancer was not locally advanced at diagnosis. This is left to investigator judgement, but generally should exclude patients with fixed tumors, fixed nodes, peau d'orange skin changes, skin ulcerations or inflammatory changes (T4 disease).
  • Patient Is currently free of breast cancer (no evidence of disease). This is also left to investigator judgement, but generally should include no evidence of distant disease on chest x-ray or mgmmogram of the opposite breast prior to registration, within 3 months prior to surgery; and no gross or microscopically positive surgical margins noted in the final surgery or pathology reports. Patients with synchronous bilateral breast cancer may be considered, provided both breasts are treated with curative intent and that eligibility is based on the side with the most adverse prognostic features.
  • Registration must be within 84 days of mastectomy, or within 84 days of axillary dissection if the patient's most extensive breast surgery was a breast sparing procedure. Patients not having mastectomy or breast sparing surgery are ineligible. Patients must not have had prior chemotherapy for this breast cancer. Patients must not have had systemic therapy of any type for a previous breast cancer.
  • Patients must not have had external beam radiotherapy for this breast cancer prior to registration. Brachytherapy (interstitial radiation therapy) at the time of breast sparing procedure is acceptable and would not render the patient Ineligible. (If external beam radiotherapy is planned to be given with brachytherapy, it must be delayed until after chemotherapy is complete.) Patients whose most extensive breast surgery was a breast sparing procedure must be planning to receive radiotherapy after chemotherapy is complete.
  • Patients must have adequate hematologic, hepatic, renal and cardiac function for high dose chemotherapy and adequate health for long-term follow-up. This must Include normal WBC (2 4,0001pl). neutrophll count (2 1,50O/pl), platelet count (2 Institutional lower limit of normal), and LVEF (left ventricular ejection fraction by institutional criteria); bilirubin within 1.5 times institutional upper limit of normal; creatinine within 1.5 times institutional upper limit of normal; and no serious disease other than breast cancer.
  • Pregnant or nursing women may not participate. Men are ineligible. Women of childbearing potential must be planning to use effective contraception.
  • All patients must be informed of the Investigational nature of this study and give written informed consent in accordance with institution and federal guidelines.
  • At the time of registration, the date of institutional review board approval for this study must be provided to the Statistical Center.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00590785

Locations
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Cancer and Leukemia Group B
Investigators
Principal Investigator: Clifford Hudis, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00590785     History of Changes
Other Study ID Numbers: 96-041, INT 0137, CALGB 9394
Study First Received: December 26, 2007
Last Updated: November 21, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
High Risk
Breast Cancer
Positive Nodes
Cyclophosphamide
Doxorubicin
96-041

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Ciprofloxacin
Cyclophosphamide
Doxorubicin
Tamoxifen
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Infective Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Antineoplastic Agents, Hormonal
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on April 21, 2014