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Combination Chemotherapy in Treating Patients With Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00003088
First received: November 1, 1999
Last updated: July 1, 2016
Last verified: July 2016
  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 Alliance for Clinical Trials in Oncology:

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

Enrollment: 2005
Study Start Date: September 1997
Study Completion Date: June 2003
Primary Completion Date: April 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sequential chemotherapy 21 days
Patients received doxorubicin 60 mg/m^2 every 3 weeks for four cycles followed by paclitaxel 175 mg/m^2 every 3 weeks for four cycles followed by cyclophosphamide 600 mg/m^2 every 3 weeks for four cycles.
Drug: cyclophosphamide
given IV
Drug: doxorubicin hydrochloride
given IV
Drug: paclitaxel
given IV
Experimental: Concurrent chemotherapy 14 days
Patients received doxorubicin 60 mg/m^2 plus cyclophosphamide 600 mg/m^2 every 2 weeks for four cycles followed by paclitaxel 175 mg/m^2 every 2 weeks for four cycles with filgrastim days 3 to 10 of each cycle at 5 µg/kg rounded to either 300 or 480 µg total dose.
Drug: cyclophosphamide
given IV
Drug: doxorubicin hydrochloride
given IV
Drug: paclitaxel
given IV
Experimental: Sequential chemotherapy 14 days
Patients received doxorubicin 60 mg/m2 every 2 weeks for four cycles followed by paclitaxel 175 mg/m2 every 2 weeks for four cycles followed by cyclophosphamide 600 mg/m2 every 2 weeks for four cycles, with filgrastim days 3 to 10 of each cycle (a total of seven doses) at 5 µg/kg, which could be rounded to either 300 or 480 µg total dose.
Drug: cyclophosphamide
given IV
Drug: doxorubicin hydrochloride
given IV
Drug: paclitaxel
given IV
Experimental: Concurrent chemotherapy 21 days
Patients received doxorubicin 60 mg/m^2 plus cyclophosphamide 600 mg/m^2 every 3 weeks for four cycles followed by paclitaxel 175 mg/m^2 every 3 weeks for four cycles.
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   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria
  1. Required Tumor Parameters

    1.1 Patients with operable, histologically confirmed adenocarcinoma of the female breast and positive lymph nodes. Node positivity may be determined by either an axillary node dissection or a positive sentinel node finding by immunohistochemistry or histology. This includes any patient with one or more positive lymph nodes whose tumors are T0, T1, 2 or 3 and N1, N2, MO. Patients with metaplastic carcinoma are eligible. Bilateral disease does not exclude patients from entry.

    1.2 Tumors that are locally advanced at diagnosis are not eligible. This is left to investigator judgment. Patients with tumors fixed to the chest wall, peau d'orange skin changes, skin ulcerations, or clinical inflammatory changes (T4 disease) are excluded from this study. Dermal lymphatic involvement noted on pathology without clinical inflammatory changes will not exclude a patient from this study.

    1.3 Patients with any ERP/PgR status are eligible.

  2. Prior treatment:

    2.1 <84 days from mastectomy or within 84 days of axillary dissection if the patient's most extensive breast surgery was a breast sparing procedure.

    2.2 Surgical resection margins - All tumor should be removed by either a modified radical mastectomy or a segmental mastectomy. Node dissection: patients may have had either an axillary node dissection or sentinel lymph node biopsy before beginning treatment on protocol.

    • Mastectomy: There should be no evidence of gross or microscopic tumor at the surgical resection margins noted in the final surgery or pathology reports for patients who have had a modified radical mastectomy. Patients with close margins (tumor < 1 mm from margin) are eligible.
    • Segmental mastectomy (lumpectomy): Although clear margins are preferable, DCIS or LCIS at the surgical resection margin will not render a patient who has undergone a segmental mastectomy ineligible for this study. Invasive tumor at the final resection margin will render a patient ineligible.

    2.3 No prior chemotherapy.

    2.4 No prior radiation therapy for this malignancy. Patients who received radiation to the breast for DCIS are eligible. Patients who have had segmental mastectomy will be treated with radiotherapy according to standard procedures in the treating physician's institution after completion of all chemotherapy. Patients who have had modified radical mastectomy may also receive radiotherapy at the discretion of the treating physician according to institutional guidelines.

    2.5 Patients may receive up to four weeks of tamoxifen therapy for this malignancy and still be eligible for study entry. Patients who received tamoxifen for purposes of chemoprevention (e.g., Breast Cancer Prevention Trial) or for other indications (including previous breast cancer) are eligible. Tamoxifen therapy should be discontinued before the patient is enrolled on this study.

  3. Age > 18. There is no upper age limit for enrollment on this study.
  4. Required initial laboratory data:

    • Granulocyte count > 1000/mm3
    • Platelet count > 100,000/mm3
    • Bilirubin within upper limits of normal
  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
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
Study Chair: Marc L. Citron, MD ProHEALTH Care Associates, LLP
  More 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: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00003088     History of Changes
Other Study ID Numbers: CALGB-9741  U10CA031946  CDR0000065788 
Study First Received: November 1, 1999
Last Updated: July 1, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Alliance for Clinical Trials in Oncology:
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
Albumin-Bound Paclitaxel
Doxorubicin
Cyclophosphamide
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on December 02, 2016