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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00041119
First received: July 8, 2002
Last updated: July 23, 2015
Last verified: July 2015
  Purpose

This randomized phase III trial studies cyclophosphamide and doxorubicin hydrochloride compared with paclitaxel as adjuvant therapy in treating breast cancer in women with 0-3 positive axillary lymph nodes. Giving additional cancer treatment after surgery may help to lower the risk that the cancer will come back (adjuvant therapy). Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether the standard adjuvant therapy of cyclophosphamide and doxorubicin hydrochloride is more effective than paclitaxel in treating women with 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
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
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 Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Duration of DFS [ Time Frame: up to 6.4 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: up to 15 years ] [ Designated as safety issue: No ]
  • Incidence of adverse events, graded according to the revised National Cancer Institute Common Terminology Criteria for Adverse Events 4.0 [ Time Frame: Up to 6 weeks post-treatment ] [ Designated as safety issue: Yes ]
  • Time to distant metastases [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]
  • Local control [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]

Enrollment: 4646
Study Start Date: May 2002
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (CA for 4 courses)
Patients receive cyclophosphamide IV and doxorubicin hydrochloride IV on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Drug: AC regimen
Given IV
Drug: doxorubicin hydrochloride
Given IV
Experimental: Arm II (CA for 6 courses [closed to accrual 12/15/2007])
Patients receive cyclophosphamide IV and doxorubicin hydrochloride IV on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: AC regimen
Given IV
Drug: cyclophosphamide
Given IV
Drug: doxorubicin hydrochloride
Given IV
Experimental: Arm III (paclitaxel for 4 courses)
Patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Drug: AC regimen
Given IV
Drug: paclitaxel
Given IV
Experimental: Arm IV (paclitaxel for 6 courses [closed 12/15/2007])
Patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: AC regimen
Given IV
Drug: paclitaxel
Given IV

  Show Detailed Description

  Eligibility

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

Eligibility Criteria:

  • Patients must have histologically confirmed invasive carcinoma of the female breast, with 0-3 positive axillary lymph nodes
  • Patients must have 0-3 positive axillary lymph nodes to be eligible for this study; patients with node-negative breast cancer should have sufficiently "high risk" disease to warrant chemotherapy; as general guidelines, node-negative patients with tumors of >= 1 cm or estrogen or progesterone receptor negative tumors of any size may be eligible; ultimately though, the definition of "high risk" may be determined by the treating physician, and if the treating physician feels the patient warrants chemotherapy, the patient is eligible; for patients with 1-3 positive axillary nodes, the patient is eligible regardless of primary breast tumor characteristics, if in the opinion of the treating physician, chemotherapy is deemed potentially beneficial to the patient
  • If the patient has had a negative sentinel node biopsy, then no further axillary dissection is required, and the patient is determined to be node-negative; if an axillary dissection, without a sentinel node biopsy, is performed to determine nodal status, at least six axillary lymph nodes must be removed and analyzed and negative for the patient to be considered node-negative; axillary nodes with single cells or tumor clusters =< 0.2 mm by either hematoxylin and eosin stain (H&E) or immunohistochemistry (IHC), will be considered node-negative; lymph nodes positive for polymerase chain reaction (PCR) with tumor cells/clusters =< 0.2 mm will be considered node-negative; any axillary lymph node with tumor clusters > 0.2 mm will be considered positive
  • If the patient has a sentinel node biopsy and one of the sentinel nodes is positive, as defined by tumor clusters > 0.2 mm, an axillary dissection must be performed; a total of at least 6 axillary lymph nodes, including sentinel nodes plus the subsequent dissection, must be removed for the patient to be eligible; of all the lymph nodes removed from both the sentinel node procedure and the axillary dissection, 1-3 must be positive for the patient to be eligible as a node-positive patient; if an axillary dissection is done without a sentinel node procedure, at least 6 lymph nodes must be removed and a 1-3 nodes must be positive for the patient to be considered node-positive and eligible for this study
  • Determination of involvement of axillary nodes with metastatic cancer will follow the revised tumor-node-metastasis (TNM) staging system: axillary nodes with single cells with tumor clusters =< 0.2 mm, by either H&E or immunohistochemistry (IHC), will be considered negative axillary node; lymph nodes positive for PCR with tumor cells/clusters < 0.2 mm will be considered negative axillary node; any axillary lymph node with clusters > 0.2 mm will be considered to be positive
  • Patients with estrogen-receptor and/or progesterone receptor negative, positive, or unknown tumors are eligible; estrogen-receptor (ER) and progesterone receptor (PgR) assays should be performed by immunohistochemical methods according to the local institution's standard protocol
  • Patients with human epidermal growth factor receptor 2 (HER2) positive, negative or unknown disease are eligible for this trial; patients whose tumors are HER2 positive by either immunohistochemistry 3+ staining or demonstrate gene amplification by fluorescence in situ hybridization (FISH) may receive trastuzumab
  • There must be negative tumor margins for invasive cancer and ductal carcinoma in situ (DCIS) in the case of mastectomy or lumpectomy; lobular carcinoma in situ (LCIS) is acceptable at the margin
  • Patients with multi-centric breast cancer are eligible as long as all known disease is resected with negative margins, and have 0-3 positive axillary lymph nodes
  • Patients must be registered within 84 days of the last breast surgery; patients must have undergone either modified radical mastectomy or lumpectomy; for patients undergoing sentinel node sampling or axillary dissection a simple mastectomy is acceptable; lumpectomy patients must receive radiation therapy; for patients treated with radiation therapy prior to chemotherapy, the patients should be registered on this study after the conclusion of radiation, with chemotherapy administration beginning within 7 days of registration

    * All primary breast and axillary node surgery must be completed prior to enrollment on study

  • No previous trastuzumab, chemotherapy or hormonal therapy for this malignancy, except for tamoxifen therapy
  • No previous anthracycline chemotherapy for any disease
  • Patients with locally advanced breast cancer, inflammatory breast cancer or metastatic breast cancer are not eligible; patients with involvement of dermal lymphatics on pathology are not eligible, even if there are no clinical signs of inflammatory cancer
  • Patients with bilateral, synchronous invasive breast cancer are eligible as long as both primary tumors; if a patient has an invasive cancer on one side that meets the eligibility criteria, and DCIS or LCIS on the contralateral side, the patient is eligible; DCIS or LCIS should be managed according to institutional guidelines
  • Patients must be disease free from prior malignancies for > 5 years, except for curatively treated basal cell or squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix; patients with a history of invasive breast cancer, or DCIS are eligible if they have been disease free for > 5 years; patients with a history of LCIS are eligible regardless of the interval from diagnosis
  • Common Toxicity Criteria (CTC) performance status 0-1
  • Women must not be pregnant or nursing
  • Concomitant exogenous hormone therapy, including oral contraceptives, post-menopausal hormone replacement therapy, and raloxifene must be stopped before patients can be enrolled
  • Patients may have received up to 4 weeks of tamoxifen therapy for this malignancy and still be eligible for this study; patients who received tamoxifen or another selective estrogen receptor modulator (SERM) for prevention or for other indicators (e.g. osteoporosis) are eligible; tamoxifen therapy or other SERMs must be discontinued before the patient is enrolled on this study

    * The use of bisphosphonates for the treatment of osteoporosis is permitted; the use of raloxifene is not permitted are enrollment on this study

  • Patients must have adequate organ function including no active congestive heart failure, and no myocardial infarction < 6 months from time of registration
  • Absolute neutrophil count (ANC) >= 1,000/mm^3
  • Platelet count >= 100,00/mm^3
  • Creatinine =< 2.0 mg/dl
  • Bilirubin =< 1.5 x upper limits of institutional normal
  • Patients may be enrolled on adjuvant bisphosphonate studies; patients may be enrolled concurrently or sequentially on 40101 and bisphosphonate trials
  • Patients may be enrolled on adjuvant hormonal studies approved by CALGB or Cancer Trials Support Unit (CTSU), such as the Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT) trials
  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
Alliance for Clinical Trials in Oncology
Investigators
Study Chair: Lawrence N. Shulman, MD Dana-Farber Cancer Institute
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00041119     History of Changes
Obsolete Identifiers: NCT00698217
Other Study ID Numbers: CALGB-40101, CDR0000069444, NCI-2009-00474, U10CA180821
Study First Received: July 8, 2002
Last Updated: July 23, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Alliance for Clinical Trials in Oncology:
stage IB breast cancer
stage II breast cancer

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

ClinicalTrials.gov processed this record on August 03, 2015