Combination Chemotherapy in Treating Patients With Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
North Central Cancer Treatment Group
Eastern Cooperative Oncology Group
Southwest Oncology Group
Information provided by (Responsible Party):
Cancer and Leukemia Group B
ClinicalTrials.gov Identifier:
NCT00003088
First received: November 1, 1999
Last updated: April 10, 2012
Last verified: March 2011
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving drugs at different times or combining more than one drug may kill more tumor cells. It is not yet known which chemotherapy regimen is more effective for breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy consisting of either doxorubicin, cyclophosphamide, or paclitaxel given at different times with that of combination chemotherapy consisting of doxorubicin plus cyclophosphamide followed by paclitaxel in treating women with stage II or stage IIIA breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: paclitaxel
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase III Trial of Sequential Chemotherapy Using Doxorubicin, Paclitaxel, and Cyclophosphamide or Concurrent Doxorubicin and Cyclophosphamide Followed by Paclitaxel at 14 or 21 Day Intervals in Women With Node Positive Stage II/IIIA Breast Cancer

Resource links provided by NLM:


Further study details as provided by Cancer and Leukemia Group B:

Primary Outcome Measures:
  • Disease free survival [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Enrollment: 2005
Study Start Date: September 1997
Estimated Study Completion Date: December 2014
Primary Completion Date: April 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sequential chemotherapy 21 days Drug: cyclophosphamide
given IV
Drug: doxorubicin hydrochloride
given IV
Drug: paclitaxel
given IV
Experimental: Concurrent chemotherapy 14 days Drug: cyclophosphamide
given IV
Drug: doxorubicin hydrochloride
given IV
Drug: paclitaxel
given IV
Experimental: Sequential chemotherapy 14 days Drug: cyclophosphamide
given IV
Drug: doxorubicin hydrochloride
given IV
Drug: paclitaxel
given IV
Experimental: Concurrent chemotherapy 21 days Drug: cyclophosphamide
given IV
Drug: doxorubicin hydrochloride
given IV
Drug: paclitaxel
given IV

Detailed Description:

OBJECTIVES: I. Compare the sequential chemotherapy with doxorubicin, paclitaxel and cyclophosphamide to combined doxorubicin and cyclophosphamide followed by paclitaxel for disease free and overall survival in women with node positive stage II or IIIA breast cancer. II. Determine whether increasing the dose density of adjuvant chemotherapy will improve disease free and overall survival. III. Compare the toxicity in patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are randomized into one of four arms (sequential chemotherapy every 2 weeks vs every 3 weeks vs concurrent chemotherapy followed by paclitaxel every 2 weeks vs every 3 weeks). All tumor should be removed by either a modified radical mastectomy or a segmental mastectomy plus axillary node dissection. Adjuvant chemotherapy is started within 84 days following the last surgical procedure. Arm I: Patients receive sequential chemotherapy every 3 weeks. Doxorubicin IV is administered once every 3 weeks for 4 doses. Paclitaxel IV is then administered over 3 hours once every 3 weeks for 4 doses. Cyclophosphamide IV is administered once every 3 weeks for 4 doses following paclitaxel. Arm II: Patients receive sequential chemotherapy every 2 weeks. Doxorubicin IV is administered once every 2 weeks for 4 doses. Paclitaxel IV is then administered over 3 hours once every 2 weeks for 4 doses. Cyclophosphamide IV is administered once every 2 weeks for 4 doses following paclitaxel. Filgrastim (G-CSF) is administered by subcutaneous injection on days 3-10 after each dose of doxorubicin, paclitaxel, and cyclophosphamide. Arm III: Patients receive combination chemotherapy every 3 weeks. Combination doxorubicin IV and cyclophosphamide IV is administered once every 3 weeks for 4 doses. Paclitaxel IV is administered over 3 hours once every 3 weeks for 4 doses following combination chemotherapy. Arm IV: Patients receive combination chemotherapy every 2 weeks. Combination doxorubicin IV and cyclophosphamide IV is administered once every 2 weeks for 4 doses. Paclitaxel IV is administered over 3 hours once every 2 weeks for 4 doses following combination chemotherapy. G-CSF is administered by subcutaneous injection on days 3-10 after each dose of doxorubicin/cyclophophamide and after each dose of paclitaxel. After completion of all chemotherapy, patients receive tamoxifen orally for 5 years. Patients undergo radiotherapy 4-6 weeks after the completion of chemotherapy. Patients are followed every 6 months for 5 years, then annually until death.

PROJECTED ACCRUAL: A total of 2,000 patients will be accrued for this study within 22 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS: Histologically diagnosed operable, stage II or IIIA adenocarcinoma of the breast One or more positive lymph nodes (T0-3, N1-2, and M0) Metaplastic carcinoma allowed Bilateral breast cancer allowed No metastatic disease Not locally advanced and no tumors fixed to the chest wall, peau d'orange skin changes, skin ulcerations, or clinical inflammatory changes Hormone receptor status: Not specified

PATIENT CHARACTERISTICS: Age: 18 and over Sex: Female Menopausal status: Not specified Performance status: Not specified Life expectancy: Not specified Hematopoietic: Granulocyte count at least 1000/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin within upper limits of normal Renal: Not specified Cardiovascular: No uncontrolled or severe cardiovascular disease No myocardial infarction within 6 months No congestive heart failure Other: No other serious medical illness No psychoses No active uncontrolled bacterial, viral, or fungal infection HIV negative Not pregnant

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: No greater than 4 weeks of prior tamoxifen therapy for malignancy No concurrent tamoxifen therapy Radiotherapy: No prior radiation therapy for this malignancy Surgery: No greater than 84 days since prior mastectomy or axillary dissection

  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: NCT00003088

Locations
United States, Arizona
CCOP - Scottsdale Oncology Program
Scottsdale, Arizona, United States, 85259-5404
United States, Illinois
CCOP - Illinois Oncology Research Association
Peoria, Illinois, United States, 61602
CCOP - Carle Cancer Center
Urbana, Illinois, United States, 61801
United States, Iowa
CCOP - Cedar Rapids Oncology Project
Cedar Rapids, Iowa, United States, 52403-1206
CCOP - Iowa Oncology Research Association
Des Moines, Iowa, United States, 10309-1016
Siouxland Hematology-Oncology
Sioux City, Iowa, United States, 51101-1733
United States, Louisiana
CCOP - Ochsner
New Orleans, Louisiana, United States, 70121
United States, Michigan
CCOP - Ann Arbor Regional
Ann Arbor, Michigan, United States, 48106
United States, Minnesota
CCOP - Duluth
Duluth, Minnesota, United States, 55805
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
CentraCare Clinic
Saint Cloud, Minnesota, United States, 56303
United States, Nebraska
CCOP - Missouri Valley Cancer Consortium
Omaha, Nebraska, United States, 68131
United States, North Dakota
Quain & Ramstad Clinic, P.C.
Bismarck, North Dakota, United States, 58501
CCOP - Merit Care Hospital
Fargo, North Dakota, United States, 58122
Altru Health Systems
Grand Forks, North Dakota, United States, 58201
United States, Ohio
CCOP - Toledo Community Hospital Oncology Program
Toledo, Ohio, United States, 43623-3456
United States, South Dakota
Rapid City Regional Hospital
Rapid City, South Dakota, United States, 57709
CCOP - Sioux Community Cancer Consortium
Sioux Falls, South Dakota, United States, 57105-1080
Canada, Saskatchewan
Saskatchewan Cancer Agency
Regina, Saskatchewan, Canada, S4S 6X3
Sponsors and Collaborators
Cancer and Leukemia Group B
North Central Cancer Treatment Group
Eastern Cooperative Oncology Group
Southwest Oncology Group
Investigators
Study Chair: Marc L. Citron, MD ProHEALTH Care Associates, LLP - Lake Success
Study Chair: James N. Ingle, MD Mayo Clinic
Study Chair: Nancy E. Davidson, MD Sidney Kimmel Comprehensive Cancer Center
Study Chair: Silvana Martino, DO Van Nuys Breast Center
  More Information

Additional Information:
Publications:
Citron ML, Berry DA, Cirrincione C, et al.: Dose-dense (DD) AC followed by paclitaxel is associated with moderate, frequent anemia compared to sequential (S) and/or less DD treatment: update by CALGB on Breast Cancer Intergroup Trial C9741 with ECOG, SWOG, & NCCTG. [Abstract] J Clin Oncol 23 (Suppl 16): A-620, 33s, 2005.
Hudis C, Citron M, Berry D, et al.: Five year follow-up of INT C9741: dose-dense (DD) chemotherapy (CRx) is safe and effective. [Abstract] Breast Cancer Research and Treatment 94 (Suppl 1): A-41, 2005.
Citron M, Berry D, Cirrincione C, et al.: Superiority of dose-dense (DD) over conventional scheduling (CS) and equivalence of sequential (SC) vs. combination adjuvant chemotherapy (CC) for node-positive breast cancer (CALGB 9741, INT C9741). [Abstract] Breast Cancer Res Treat 76 (Suppl 1): A-15, 2002.
Muss H, Berry D, Cirrincione C, et al.: Toxicity of older and younger patients (pts) treated (Rx) with intensive adjuvant chemotherapy (Cx) for node-positive (N+) breast cancer (BC): the CALGB experience. [Abstract] J Clin Oncol 24 (Suppl 18): A-559, 2006.
Berry DA, Cirrincione C, Henderson IC, et al.: Effects of improvements in chemotherapy on disease-free and overall survival of estrogen-receptor negative, node-positive breast cancer: 20-year experience of the CALGB U.S. Breast Intergroup. [Abstract] Breast Cancer Res Treat 88 (Suppl 1): A-29, 2004.

Responsible Party: Cancer and Leukemia Group B
ClinicalTrials.gov Identifier: NCT00003088     History of Changes
Other Study ID Numbers: CDR0000065788, U10CA031946, CLB-9741, E-C9741, NCCTG-C9741, SWOG-C9741
Study First Received: November 1, 1999
Last Updated: April 10, 2012
Health Authority: United States: Federal Government

Keywords provided by Cancer and Leukemia Group B:
stage II breast cancer
stage IIIA breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Liposomal doxorubicin
Cyclophosphamide
Doxorubicin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 19, 2014