Four Versus Six Cycles of Cyclophosphamide/Doxorubicin or Paclitaxel in Adjuvant Breast Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2010 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00041119
First received: July 8, 2002
Last updated: September 17, 2010
Last verified: August 2010
  Purpose

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, and paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known whether giving cyclophosphamide together with doxorubicin is more effective than giving paclitaxel alone in treating breast cancer.

PURPOSE: This randomized phase III trial is studying cyclophosphamide and doxorubicin to see how well they work compared to paclitaxel in treating women with invasive breast cancer.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: Cyclophosphamide And Doxorubicin (CA) (4 VS 6 Cycles) Versus Paclitaxel (4 VS 6 Cycles) As Adjuvant Therapy For Breast Cancer in Women With 0-3 Positive Axillary Lymph Nodes:A 2X2 Factorial Phase III Randomized Study

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Disease-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]
  • Myelosuppression in patients with MDR1 haplotypes [ Designated as safety issue: No ]
  • CYP3A5, CYP2C8, and CYP2B6 polymorphisms [ Designated as safety issue: No ]

Estimated Enrollment: 4646
Study Start Date: May 2002
Estimated Primary Completion Date: October 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I
Patients receive doxorubicin IV and cyclophosphamide IV on day 1. Treatment repeats every 14 days for 4 courses.
Drug: AC regimen
Given IV
Drug: cyclophosphamide
Given IV
Drug: doxorubicin hydrochloride
Given IV
Experimental: Arm II (closed to accrual as of 1/30/2008)
Patients receive doxorubicin and cyclophosphamide as in arm I. Treatment repeats every 14 days for 6 courses.
Drug: AC regimen
Given IV
Drug: cyclophosphamide
Given IV
Drug: doxorubicin hydrochloride
Given IV
Experimental: Arm III
Patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 14 days for 4 courses.
Drug: paclitaxel
Given IV
Experimental: Arm IV (closed to accrual as of 1/30/2008)
Patients receive paclitaxel as in arm III. Treatment repeats every 14 days for 6 courses.
Drug: paclitaxel
Given IV

Detailed Description:

OBJECTIVES:

Primary

  • Compare the disease-free survival of women with operable breast cancer and 0-3 positive axillary lymph nodes treated with two different schedules (4 vs 6 courses) of adjuvant cyclophosphamide and doxorubicin vs paclitaxel. (Arms II and IV closed to accrual as of 1/30/2008)
  • Compare the disease-free survival of patients treated with these regimens.

Secondary

  • Compare overall survival, local control, and time to distant metastasis in patients treated with these regimens.
  • Compare the toxic effects of these regimens in these patients.
  • Compare the effect of these regimens on the induction of menopause in premenopausal patients.
  • Determine the discrepancy of myelosuppression in patients with MDR1 haplotypes on the CA treatment arm.
  • Compare the disease-free survival of patients with MDR1 haplotypes treated with these regimens.
  • Correlate CYP3A5, CYP2C8, and CYP2B6 polymorphisms with disease-free survival and toxicity in patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are stratified according to menopausal status (premenopausal vs postmenopausal), estrogen receptor (ER)/progesterone receptor (PR) status (ER and/or PR positive or unknown vs ER and PR negative), and HER2/neu status (negative vs unknown vs positive [by immunohistochemistry 3+ staining or gene amplification by fluorescence in situ hybridization]). Patients are randomized to 1 of 4 treatment arms (arms II and IV closed to accrual as of 1/30/2008).

  • Arm I: Patients receive doxorubicin IV and cyclophosphamide IV on day 1. Treatment repeats every 14 days for 4 courses.
  • Arm II (closed to accrual as of 1/30/2008): Patients receive doxorubicin and cyclophosphamide as in arm I. Treatment repeats every 14 days for 6 courses.
  • Arm III: Patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 14 days for 4 courses.
  • Arm IV (closed to accrual as of 1/30/2008): Patients receive paclitaxel as in arm III. Treatment repeats every 14 days for 6 courses.

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

Lumpectomy patients must then undergo radiotherapy. Mastectomy patients undergo radiotherapy at the discretion of the treating physician.

Patients are followed every 6 months for 2 years and then annually for 15 years.

PROJECTED ACCRUAL: A total of 4,646 patients will be accrued for this study within 29 months.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed invasive carcinoma of the breast with 0-3 positive axillary lymph nodes

    • Meets 1 of the following criteria for node-negative disease:

      • Negative sentinel lymph node biopsy
      • At least 6 negative axillary lymph nodes removed and determined to be negative by axillary dissection
    • Meets 1 of the following criteria for node-positive disease (1-3 positive axillary lymph nodes):

      • At least 1 positive lymph node by sentinel lymph node biopsy AND at least 6 axillary lymph nodes removed by axillary dissection; of all the nodes removed from both the sentinel lymph node biopsy and the axillary dissection, 1-3 must be positive
      • At least 6 lymph nodes removed by axillary dissection; 1-3 nodes from the axillary dissection must be positive
  • "High-risk" disease that warrants chemotherapy (ultimately determined by the treating physician)
  • Modified radical mastectomy or lumpectomy within the past 84 days required

    • Negative tumor margins for invasive cancer and ductal carcinoma in situ (DCIS)
    • Lobular carcinoma in situ (LCIS) at the margin allowed
  • Multicentric disease allowed provided margins and axillary nodes are negative after resection
  • Bilateral synchronous disease allowed
  • Invasive cancer on one side and DCIS or LCIS on the contralateral side is allowed provided all other eligibility criteria are met
  • No locally advanced, inflammatory, or metastatic breast cancer
  • No dermal lymphatics involvement, even if there are no clinical signs of inflammatory cancer
  • HER2/neu positive, negative, or unknown
  • Hormone receptor status:

    • Any estrogen and/or progesterone receptor status

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Sex:

  • Female

Menopausal status:

  • Premenopausal or postmenopausal

Performance status:

  • CTC 0-1

Life expectancy:

  • Not specified

Hematopoietic:

  • Absolute neutrophil count at least 1,000/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic:

  • Bilirubin no greater than 1.5 times upper limit of normal

Renal:

  • Creatinine no greater than 2.0 mg/dL

Cardiovascular:

  • No active congestive heart failure
  • No myocardial infarction within the past 6 months

Other:

  • Not pregnant or nursing
  • Fertile patients must use effective nonhormonal contraception during and for at least 2 months after study participation
  • No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No prior trastuzumab (Herceptin^®) for this malignancy

Chemotherapy:

  • See Disease Characteristics
  • No prior chemotherapy for this malignancy
  • No other concurrent chemotherapy

Endocrine therapy:

  • No prior hormonal therapy for this malignancy except tamoxifen given for up to 4 weeks
  • Prior tamoxifen or other selective estrogen receptor modulators (SERMs) for prevention or other indications (e.g., osteoporosis) allowed
  • No concurrent exogenous hormonal therapy (including oral contraceptives, postmenopausal hormone replacement therapy, or raloxifene) except:

    • Steroids for adrenal failure
    • Hormonal agents for nondisease-related conditions (e.g., insulin for diabetes or synthroid for hypothyroidism)
    • Intermittent dexamethasone as an antiemetic and premedication for paclitaxel
  • No concurrent tamoxifen or other SERMs

Surgery:

  • See Disease Characteristics

Other:

  • No concurrent dexrazoxane
  • No concurrent raloxifene
  • Concurrent bisphosphonates for osteoporosis allowed
  • Concurrent trastuzumab (Herceptin^®) allowed for patients with HER2-positive disease
  • Concurrent enrollment on adjuvant bisphosphonate studies allowed
  • Concurrent enrollment on adjuvant hormonal studies allowed provided hormonal therapy does not commence until completion of study chemotherapy
  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: NCT00041119

  Show 527 Study Locations
Sponsors and Collaborators
Cancer and Leukemia Group B
Investigators
Study Chair: Lawrence N. Shulman, MD Dana-Farber Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Monica M. Bertagnolli, Cancer and Leukemia Group B
ClinicalTrials.gov Identifier: NCT00041119     History of Changes
Obsolete Identifiers: NCT00698217
Other Study ID Numbers: CDR0000069444, CALGB-40101
Study First Received: July 8, 2002
Last Updated: September 17, 2010
Health Authority: United States: Federal Government

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

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Doxorubicin
Paclitaxel
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
Antibiotics, Antineoplastic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on July 28, 2014