Combination Chemotherapy in Treating Patients With Breast Cancer

NCT ID: NCT00003088

Last Updated: 2020-04-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

2005 participants

Study Classification

INTERVENTIONAL

Study Start Date

1997-09-30

Study Completion Date

2003-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

cyclophosphamide

Intervention Type DRUG

given IV

doxorubicin hydrochloride

Intervention Type DRUG

given IV

paclitaxel

Intervention Type DRUG

given IV

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.

Group Type EXPERIMENTAL

cyclophosphamide

Intervention Type DRUG

given IV

doxorubicin hydrochloride

Intervention Type DRUG

given IV

paclitaxel

Intervention Type DRUG

given IV

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.

Group Type EXPERIMENTAL

cyclophosphamide

Intervention Type DRUG

given IV

doxorubicin hydrochloride

Intervention Type DRUG

given IV

paclitaxel

Intervention Type DRUG

given IV

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.

Group Type EXPERIMENTAL

cyclophosphamide

Intervention Type DRUG

given IV

doxorubicin hydrochloride

Intervention Type DRUG

given IV

paclitaxel

Intervention Type DRUG

given IV

Interventions

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cyclophosphamide

given IV

Intervention Type DRUG

doxorubicin hydrochloride

given IV

Intervention Type DRUG

paclitaxel

given IV

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Marc L. Citron, MD

Role: STUDY_CHAIR

ProHEALTH Care Associates, LLP

Locations

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CCOP - Scottsdale Oncology Program

Scottsdale, Arizona, United States

Site Status

CCOP - Illinois Oncology Research Association

Peoria, Illinois, United States

Site Status

CCOP - Carle Cancer Center

Urbana, Illinois, United States

Site Status

CCOP - Cedar Rapids Oncology Project

Cedar Rapids, Iowa, United States

Site Status

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, United States

Site Status

Siouxland Hematology-Oncology

Sioux City, Iowa, United States

Site Status

CCOP - Ochsner

New Orleans, Louisiana, United States

Site Status

CCOP - Ann Arbor Regional

Ann Arbor, Michigan, United States

Site Status

CCOP - Duluth

Duluth, Minnesota, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

CentraCare Clinic

Saint Cloud, Minnesota, United States

Site Status

CCOP - Missouri Valley Cancer Consortium

Omaha, Nebraska, United States

Site Status

Quain & Ramstad Clinic, P.C.

Bismarck, North Dakota, United States

Site Status

CCOP - Merit Care Hospital

Fargo, North Dakota, United States

Site Status

Altru Health Systems

Grand Forks, North Dakota, United States

Site Status

CCOP - Toledo Community Hospital Oncology Program

Toledo, Ohio, United States

Site Status

Rapid City Regional Hospital

Rapid City, South Dakota, United States

Site Status

CCOP - Sioux Community Cancer Consortium

Sioux Falls, South Dakota, United States

Site Status

Saskatchewan Cancer Agency

Regina, Saskatchewan, Canada

Site Status

Countries

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United States Canada

References

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Muss HB, Berry DA, Cirrincione C, Budman DR, Henderson IC, Citron ML, Norton L, Winer EP, Hudis CA; Cancer and Leukemia Group B Experience. Toxicity of older and younger patients treated with adjuvant chemotherapy for node-positive breast cancer: the Cancer and Leukemia Group B Experience. J Clin Oncol. 2007 Aug 20;25(24):3699-704. doi: 10.1200/JCO.2007.10.9710.

Reference Type BACKGROUND
PMID: 17704418 (View on PubMed)

Berry DA, Cirrincione C, Henderson IC, Citron ML, Budman DR, Goldstein LJ, Martino S, Perez EA, Muss HB, Norton L, Hudis C, Winer EP. Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA. 2006 Apr 12;295(14):1658-67. doi: 10.1001/jama.295.14.1658.

Reference Type BACKGROUND
PMID: 16609087 (View on PubMed)

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.

Reference Type BACKGROUND

Campone M, Fumoleau P, Bourbouloux E, Kerbrat P, Roche H. Taxanes in adjuvant breast cancer setting: which standard in Europe? Crit Rev Oncol Hematol. 2005 Sep;55(3):167-75. doi: 10.1016/j.critrevonc.2005.04.003.

Reference Type BACKGROUND
PMID: 16039867 (View on PubMed)

Orzano JA, Swain SM. Concepts and clinical trials of dose-dense chemotherapy for breast cancer. Clin Breast Cancer. 2005 Dec;6(5):402-11. doi: 10.3816/CBC.2005.n.044.

Reference Type BACKGROUND
PMID: 16381623 (View on PubMed)

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.

Reference Type BACKGROUND

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.

Reference Type RESULT

Fornier M, Norton L. Dose-dense adjuvant chemotherapy for primary breast cancer. Breast Cancer Res. 2005;7(2):64-9. doi: 10.1186/bcr1007. Epub 2005 Feb 10.

Reference Type RESULT
PMID: 15743513 (View on PubMed)

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.

Reference Type RESULT

Schwartz J, Domchek SM, Hwang WT, Fox K. Evaluation of anemia, neutropenia and skin toxicities in standard or dose-dense doxorubicin/cyclophosphamide (AC)-paclitaxel or docetaxel adjuvant chemotherapy in breast cancer. Ann Oncol. 2005 Feb;16(2):247-52. doi: 10.1093/annonc/mdi058.

Reference Type RESULT
PMID: 15668278 (View on PubMed)

Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, Davidson NE, Martino S, Livingston R, Ingle JN, Perez EA, Carpenter J, Hurd D, Holland JF, Smith BL, Sartor CI, Leung EH, Abrams J, Schilsky RL, Muss HB, Norton L. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003 Apr 15;21(8):1431-9. doi: 10.1200/JCO.2003.09.081. Epub 2003 Feb 13.

Reference Type RESULT
PMID: 12668651 (View on PubMed)

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.

Reference Type RESULT

Metzger Filho O, Ballman K, Campbell J, Liu M, Ligibel J, Watson M, Chen E, Du L, Stover D, Carey L, Partridge A, Kirshner J, Muss H, Hudis C, Winer EP, Norton L, Symmans WF. Adjuvant Dose-Dense Chemotherapy in Hormone Receptor-Positive Breast Cancer. J Clin Oncol. 2025 Apr;43(10):1229-1239. doi: 10.1200/JCO-24-01875. Epub 2025 Jan 2.

Reference Type DERIVED
PMID: 39746162 (View on PubMed)

Related Links

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https://nctn-data-archive.nci.nih.gov/

Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive

Other Identifiers

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U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CALGB-9741

Identifier Type: -

Identifier Source: secondary_id

CDR0000065788

Identifier Type: REGISTRY

Identifier Source: secondary_id

CALGB-9741

Identifier Type: -

Identifier Source: org_study_id

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