NCT01547741|UnknownPhase 3DMC

Docetaxel and Cyclophosphamide Compared to Anthracycline-Based Chemotherapy in Treating Women With HER2-Negative Breast Cancer

A Phase III Clinical Trial Comparing the Combination of Docetaxel Plus Cyclophosphamide to Anthracycline-Based Chemotherapy Regimens for Women With Node-Positive or High-Risk Node-Negative, HER2-Negative Breast Cancer

NSABP Foundation Inc ClinicalTrials.gov

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2 other identifiers

NSABP-B-49NCI-2012-00701

Study Type

interventional

Target

1,871

Locations

2 countries

Sites

915

Timeline

RegisteredMar 2012

StartedApr 2012

CompletionNov 2023

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of breast cancer cells, either by killing the cells or by stopping them from dividing. Giving the drugs in different combinations may kill more breast cancer cells. Giving combination chemotherapy after surgery may kill any tumor cells that remain after surgery. PURPOSE: This randomized phase III trial is studying different combination chemotherapy regimens and their side effects and comparing how well they work in treating women with non-metastatic breast cancer.

Trial Health

At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date

Enrollment

1,871

participants targeted

Target at P75+ for phase_3 breast-cancer

Timeline

Completed

Started Apr 2012

Longer than P75 for phase_3 breast-cancer

Geographic Reach

2 countries

915 active sites

Status

unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

11.6 years study duration

First Submitted

Initial submission to the registry

March 6, 2012

Completed

2 days until next milestone

First Posted

Study publicly available on registry

March 8, 2012

Completed

24 days until next milestone

Study Start

First participant enrolled

April 1, 2012

Completed

10.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2022

Completed

1.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2023

Completed

Last Updated

April 14, 2022

Status Verified

April 1, 2022

Enrollment Period

10.1 years

First QC Date

March 6, 2012

Last Update Submit

April 13, 2022

Conditions

Breast Cancer

Keywords

estrogen receptor-negative breast cancerestrogen receptor-positive breast cancerHER2-negative breast cancerprogesterone receptor-negative breast cancerprogesterone receptor-positive breast cancerstage IA breast cancerstage IB breast cancerstage II breast cancerstage IIIA breast cancerstage IIIC breast cancer

Outcome Measures

Primary Outcomes (1)

Invasive disease-free survival (IDFS)
The time to local recurrence following mastectomy, invasive local recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, invasive contralateral breast cancer, second primary cancer (other than squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix, colorectal carcinoma in situ, or lobular carcinoma in situ of the breast), or death from any cause prior to recurrence or second primary cancer.
Assessed before each cycle of chemotherapy, 3-4 weeks after completion of chemotherapy, every 6 months through 5 years and yearly years 6-10.

Secondary Outcomes (5)

Disease-free survival (DFS-DCIS)
Assessed before each cycle of chemotherapy, 3-4 weeks after completion of chemotherapy, every 6 months through 5 years and yearly years 6-10.
Overall survival (OS)
Assessed before each cycle of chemotherapy, 3-4 weeks after completion of chemotherapy, every 6 months through 5 years and yearly years 6-10.
Recurrence-free interval (RFI)
Assessed before each cycle of chemotherapy, 3-4 weeks after completion of chemotherapy, every 6 months through 5 years and yearly years 6-10.
Toxicity of each regimen
Assessed before each cycle of chemotherapy, 3-4 weeks after completion of chemotherapy, every 6 months through 5 years and yearly years 6-10.
Molecular predictors of efficacy
Tissue sample collected at time of surgery

Study Arms (2)

Arm 1: Anthracycline-based chemotherapy

ACTIVE COMPARATOR

4 anthracycline-based chemotherapy regimens (Regimens A, B, C, or D). Regimen A (TAC): 75 mg/m2 docetaxel (T) + 50 mg/m2 doxorubicin (A) + 500 mg/m2 cyclophosphamide (C) IV every 3 weeks for 6 cycles. Regimen B (AC then WP): 60 mg/m2 doxorubicin (A) + 600 mg/m2 cyclophosphamide (C) every 3 weeks for 4 cycles followed by weekly paclitaxel (WP) 80 mg/m2 IV every week for 12 doses. Regimen C (DD AC then WP): 60 mg/m2 doxorubicin + 600 mg/m2 cyclophosphamide every 2 weeks for 4 cycles followed by weekly paclitaxel 80 mg/m2 IV every week for 12 doses. Regimen D (DD AC then DD P): 60 mg/m2 doxorubicin + 600 mg/m2 cyclophosphamide every 2 weeks for 4 cycles followed by paclitaxel (P) 175 mg/m2 IV every 2 weeks for 4 cycles.

Drug: DoxorubicinDrug: CyclophosphamideDrug: DocetaxelDrug: Paclitaxel

Arm 2: docetaxel + cyclophosphamide

ACTIVE COMPARATOR

TC: 75 mg/m2 docetaxel and 600 mg/m2 cyclophosphamide IV every 3 weeks for 6 cycles

Drug: CyclophosphamideDrug: Docetaxel

Interventions

DoxorubicinDRUG

Also known as: adriamycin

Arm 1: Anthracycline-based chemotherapy

CyclophosphamideDRUG

Arm 1: Anthracycline-based chemotherapyArm 2: docetaxel + cyclophosphamide

DocetaxelDRUG

Arm 1: Anthracycline-based chemotherapyArm 2: docetaxel + cyclophosphamide

PaclitaxelDRUG

Arm 1: Anthracycline-based chemotherapy

Eligibility Criteria

Age18 Years+

Sexfemale

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination.
The breast cancer must be Human Epidermal Growth Factor Receptor 2 (HER2)-negative based on current American Society of Clinical Oncology (ASCO)/CAP Guideline Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer. If the result of the in situ hybridization testing (FISH, chromagen in situ hybridization \[CISH\], or other) is equivocal, the patient is eligible if there is no plan to administer HER2-targeted therapy.
All of the following staging criteria must be met according to American Joint Committee on Cancer (AJCC) criteria:
By pathologic evaluation, primary tumor must be pT1-3;
By pathologic evaluation, ipsilateral nodes must be pN0, pN1 (pN1mi, pN1a, pN1b, pN1c), pN2a, pN3a, or pN3b.
If pN0, at least one of the following criteria must be met:
ER negative and PgR negative; or
Pathologic tumor size greater than 2.0 cm; or
T1c (pathologic tumor size greater than 1.0 cm but less than or equal to 2.0 cm) and ER positive (PgR status may be positive or negative) and either grade 3 histology or Oncotype DX® Recurrence Score of greater than or equal to 25.
Patients must have undergone either a total mastectomy or breast-conserving surgery (lumpectomy).
For patients who undergo lumpectomy, the margins of the resected specimen must be histologically free of invasive tumor and ductal carcinoma in situ (DCIS) as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional operative procedures must be performed to obtain clear margins. If tumor is still present at the resected margin after re-excision(s), the patient must undergo total mastectomy to be eligible. (Patients with margins positive for lobular carcinoma in situ \[LCIS\] are eligible without additional resection.)
For patients who undergo mastectomy, margins must be histologically free of invasive tumor and DCIS.
Patients must have completed one of the following procedures for evaluation of pathologic nodal status:
Sentinel lymphadenectomy alone if pathologic nodal staging based on sentinel lymphadenectomy is pN0, pN1mi, or pN1b;
+17 more criteria

You may not qualify if:

Patients with one or more of the following conditions are ineligible for this study.
T4 tumors including inflammatory breast cancer.
Definitive clinical or radiologic evidence of metastatic disease. (Chest imaging \[mandatory for all patients\] and other imaging \[if required\] must have been performed within 90 days prior to randomization.)
Synchronous or previous contralateral invasive breast cancer. (Patients with synchronous and/or previous contralateral DCIS are eligible.)
Any history of ipsilateral invasive breast cancer or ipsilateral DCIS.
History of non-breast malignancies within 5 years prior to randomization, except for the following: carcinoma in situ of the cervix, colorectal carcinoma in situ, melanoma in situ, and basal cell and squamous cell carcinomas of the skin.
Previous therapy with anthracyclines or taxanes for any malignancy.
Chemotherapy administered for the currently diagnosed breast cancer prior to randomization.
Continued endocrine therapy such as raloxifene or tamoxifen (or other SERM) or an aromatase inhibitor. Patients are eligible if these medications are discontinued prior to randomization.
Any sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement therapy. Patients are eligible if these medications are discontinued prior to randomization.
Known active hepatitis B or hepatitis C with abnormal liver function tests.
Cardiac disease (history of and/or active disease) that would preclude the use of the drugs included in the treatment regimens. This includes but is not confined to:
Active cardiac disease
angina pectoris that requires the use of anti-anginal medication;
ventricular arrhythmias except for benign premature ventricular contractions;
+21 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

NSABP Foundation Inclead
National Cancer Institute (NCI)collaborator

Study Sites (915)

Providence Alaska Medical Center

Anchorage, Alaska, 99508, United States

Location

Arizona Oncology Associates-Biltmore Cancer Center

Phoenix, Arizona, 85016, United States

Location

Premiere Oncology of Arizona

Scottsdale, Arizona, 85258, United States

Location

Sedona Medical Center

Sedona, Arizona, 86336, United States

Location

Arizona Oncology Associates

Tucson, Arizona, 85704, United States

Location

NEA Baptist Clinic-Matthews

Jonesboro, Arkansas, 72401, United States

Location

Kaiser Anaheim Medical Center

Anaheim, California, 92807, United States

Location

Kaiser Permanente-Deer Valley Medical Center

Antioch, California, 94531, United States

Location

Kaiser Permanente Medical Group - Baldwin Park

Baldwin Park, California, 91706, United States

Location

Kaiser Foundation Hospital

Bellflower, California, 90706, United States

Location

Providence Saint Joseph Medical Center

Burbank, California, 91505, United States

Location

East Bay Radiation Oncology Center

Castro Valley, California, 94546, United States

Location

Valley Medical Oncology Consultants-Castro Valley

Castro Valley, California, 94546, United States

Location

Epic Care-Dublin

Dublin, California, 94568, United States

Location

Northbay Cancer Center

Fairfield, California, 94533, United States

Location

Kaiser Permanente Hospital

Fontana, California, 92335, United States

Location

Kaiser Permanente, Fremont

Fremont, California, 94538, United States

Location

Valley Medical Oncology Consultants-Fremont

Fremont, California, 94538, United States

Location

Washington Hospital

Fremont, California, 94538, United States

Location

California Cancer Center - North Fresno

Fresno, California, 93720, United States

Location

Kaiser Permanente

Fresno, California, 93720, United States

Location

Kaiser Permanente - Harbor City

Harbor City, California, 90710, United States

Location

Kaiser Permanente, Hayward

Hayward, California, 94545, United States

Location

Southern California Permanente Medical Group

Irvine, California, 92618, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Long Beach Memorial Medical Center-Todd Cancer Institute

Long Beach, California, 90806, United States

Location

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, 90027, United States

Location

Kaiser Permanente

Los Angeles, California, 90027, United States

Location

Kaiser Permanente-West Los Angeles

Los Angeles, California, 90034, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Contra Costa Regional Medical Center

Martinez, California, 94553-3156, United States

Location

Memorial Medical Center

Modesto, California, 95355, United States

Location

Kaiser Permanente-Modesto

Modesto, California, 95356, United States

Location

Community Hospital of Monterey Peninsula

Monterey, California, 93940, United States

Location

El Camino Hospital

Mountain View, California, 94040, United States

Location

Highland General Hospital

Oakland, California, 94602, United States

Location

Alta Bates Summit Medical Center - Summit Campus