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AzTrials

Breast CancerPhase 3NCT00093795

Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Positive Breast Cancer

A Phase 3 study testing Cyclophosphamide, Docetaxel and Gemcitabine in people with Breast Cancer, run by NSABP Foundation Inc at 12 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

RATIONALE: Drugs used in chemotherapy, such as docetaxel, doxorubicin , cyclophosphamide, paclitaxel, and gemcitabine work in different ways to stop tumor cells from dividing so they stop growing or die. Giving combination chemotherapy after surgery may kill any remaining tumor cells. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
Cyclophosphamide, Docetaxel and Gemcitabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4,894 participants
Where
12 sitesUnited States
Study dates
Oct 2004to Jun 2016
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The patient must consent to participate in the study and must have signed an approved consent form conforming with federal and institutional guidelines.
  • The patient must have a life expectancy of at least 10 years and a Zubrod performance status of 0 or 1. (Comorbid conditions but not the diagnosis of breast cancer should be taken into consideration when determining life expectancy.)
  • The interval between the last surgery for breast cancer staging or treatment and randomization must be no more than 84 days.
  • The tumor must be invasive carcinoma of the breast on histologic examination.
  • All of the following staging criteria must be met:
  • By clinical and pathologic evaluation, primary tumor must be T1-3;
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  • By clinical evaluation, ipsilateral nodes must be cN0, cN1, or cN2a;
  • By pathologic evaluation, ipsilateral nodes must be pN1 (pN1mi, pN1a, pN1b, pN1c), pN2a, pN3a, or pN3b (only if due to microscopic involvement of internal mammary node detected by sentinel lymph node dissection and with more than 3 positive axillary lymph nodes).
  • Patients must have an estrogen receptor (ER) analysis performed on the primary tumor prior to randomization. If ER analysis is negative, then progesterone receptor (PgR) analysis must be performed. If ER analysis is positive, PgR analysis is desired, but not mandatory. ("Marginal" or "borderline" results [i.e., those not definitely negative] will be considered positive regardless of the methodology used.)
  • Patients must have had either a lumpectomy or a total mastectomy. Patients must have completed one of the following procedures for evaluation of pathologic nodal status.
  • Sentinel lymphadenectomy followed by removal of additional non-sentinel lymph nodes (This approach is strongly recommended.)
  • Sentinel lymphadenectomy alone if one of the following criteria is met:
  • Pathologic nodal staging based on sentinel lymphadenectomy is pN1mi or pN1b
  • Surgeon elects not to remove additional non-sentinel nodes (This approach is strongly discouraged, but will not preclude participation in B-38.)
  • Axillary lymphadenectomy without sentinel node isolation procedure.
  • Patients must have no clinical or radiologic evidence of metastatic disease.
  • Patients with either skeletal pain or alkaline phosphatase that is greater than ULN but less than or equal to 2.5 x ULN are eligible for inclusion in the study if bone scans fail to demonstrate metastatic disease. Suspicious findings on bone scan must be confirmed as benign by x-ray, MRI, or biopsy.
  • Patients with aspartate transaminase (AST) or alkaline phosphatase greater than ULN are eligible for inclusion in the study if liver imaging fails to demonstrate metastatic disease and the following requirements are met at the time of randomization.
  • Postoperative absolute granulocyte count (AGC) must be greater than or equal to 1200/mm3.
  • Postoperative platelet count must be greater than or equal to 100,000/mm3.
  • The following criteria for postoperative evidence of adequate hepatic function must be met:
  • total bilirubin must be less than or equal to ULN for the lab unless the patient has a grade 1 bilirubin elevation (greater than ULN to 1.5 x ULN) due to Gilbert's disease or similar syndrome due to slow conjugation of bilirubin; and
  • alkaline phosphatase must be less than or equal to 2.5 x ULN for the lab; and
  • the AST must be less than or equal to 1.5 x ULN for the lab; and
  • alkaline phosphatase and AST cannot both be greater than ULN.
  • Postoperative serum creatinine must be less than or equal to ULN.
  • At the time of randomization, the patient must have had the following: history and physical exam, EKG, and imaging of the chest within the past 3 months and bilateral mammogram within the past 6 months.
  • Within 3 months prior to entry, the patient must have a baseline left ventricular ejection fraction (LVEF), measured by Multiple Gated Acquisition (MUGA) scan or echocardiogram, greater than or equal to lower limit of normal (LLN) for the facility performing the procedure and no evidence of regional wall abnormalities.
  • Patients with a history of non-breast malignancies are eligible if they have been disease-free for 5 or more years prior to randomization and are deemed by their physician to be at low risk for recurrence. Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinoma of the skin.
  • Special conditions for eligibility of lumpectomy patients: radiation therapy and surgery. Patients treated by lumpectomy must meet all the eligibility criteria in addition to the following:
  • Generally, lumpectomy should be reserved for tumors less than 5 cm. However, at the investigator's discretion, patients treated with lumpectomy for tumors greater than or equal to 5 cm are eligible if eligibility criteria for lumpectomy are met.
  • The margins of the resected specimen must be histologically free of invasive tumor and DCIS as determined by the local pathologist. In patients for whom pathologic examination demonstrates tumor present at the line of resection, additional operative procedures may be performed to obtain clear margins. This is permissible even if axillary evaluation has been completed. Patients in whom tumor is still present at the resected margin after re-excision(s) must undergo total mastectomy to be eligible. (Patients with margins positive for lobular carcinoma in situ (LCIS) are eligible without additional resection.)
  • Irradiation of regional lymph nodes is optional, but plans for radiation therapy must be declared by the investigator prior to randomization for stratification purposes.
  • Special conditions for eligibility of mastectomy patients: radiation therapy o Postmastectomy chest wall and/or regional nodal irradiation is optional. Plans for radiation in mastectomy patients must be declared by the investigator prior to randomization for stratification purposes.
  • Ineligibility Criteria
  • Male patients are not eligible for this study. Women with one or more of the following conditions or prior therapies are also ineligible for this study:
  • Tumor that has been determined to be human epidermal growth factor receptor 2 (HER2)-positive by immunohistochemistry (3+) or by fluorescent in situ hybridization (positive for gene amplification).
  • Contralateral breast cancer (invasive or DCIS) or a mass or mammographic abnormality in the opposite breast suspicious for malignancy unless there is biopsy proof that the mass is not malignant.
  • Primary tumor staged as T4 for any reason.
  • Clinical nodal stages including cN2b and cN3 or pathologic nodal stages including pN0(i+), pN2b, pN3b with clinically apparent internal mammary nodes, or pN3c.
  • Suspicious nodes in the contralateral axilla or suspicious supraclavicular nodes. Patients with these conditions are considered ineligible unless there is biopsy evidence that these are not involved with tumor.
  • Prior history of breast cancer, including DCIS (patients with a history of LCIS are eligible).
  • Treatment, including radiation therapy, chemotherapy, and/or hormonal therapy administered for the currently diagnosed breast cancer prior to randomization. One exception is hormonal therapy, which may have been given for up to a total of 28 days anytime after diagnosis and before study entry. In such a case, hormonal therapy must stop at or before randomization and be re-started, if indicated, following chemotherapy. A second exception is radiation therapy for patients enrolled in NSABP B-39 and assigned to partial breast irradiation (Group 2). These patients may have received RT prior to B-38 study entry.
  • Prior therapy with anthracyclines or taxanes for any malignancy.
  • Any sex hormonal therapy, e.g., birth control pills, ovarian hormonal replacement therapy, etc. (These patients are eligible if this therapy is discontinued prior to randomization.)
  • Therapy with any hormonal agents such as raloxifene (Evista®), tamoxifen, or other selective estrogen-receptor modulators (SERMs), either for osteoporosis or breast cancer prevention. (Patients are eligible only if these medications are discontinued prior to randomization.
  • Cardiac disease that would preclude the use of anthracyclines. This includes:
  • history of myocardial infarction documented by elevated cardiac enzymes or regional wall abnormalities on assessment of left ventricular (LV) function;
  • angina pectoris that requires the use of anti-anginal medication;
  • any history of documented congestive heart failure;
  • serious cardiac arrhythmia requiring medication;
  • severe conduction abnormality;
  • valvular disease with documented cardiac function compromise; and
  • uncontrolled hypertension defined as blood pressure greater than 160/100 on antihypertensive therapy.
  • Conditions that would prohibit administration of corticosteroids.
  • Sensory/motor neuropathy greater than or equal to grade 2, as defined by the NCI's Common Terminology Criteria for Adverse Events Version 3.0.
  • Non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude a patient from receiving any of the treatment options or would prevent prolonged follow-up.
  • History of hepatitis B or C.
  • Pregnancy or lactation at the time of proposed randomization. Women of reproductive potential must agree to use an effective non-hormonal method of contraception.
  • Concurrent treatment with other investigational agents for the treatment of breast cancer.
  • Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements.
  • Special conditions for ineligibility of lumpectomy patients: radiation therapy and surgery
  • For patients treated by lumpectomy, whole breast irradiation is required.
  • The following patients will be ineligible:
  • Patients with diffuse tumors (as demonstrated on mammography) treated with lumpectomy. (These patients are eligible if they undergo mastectomy.)
  • Patients treated with lumpectomy in whom there is another clinically dominant mass or mammographically suspicious abnormality within the ipsilateral breast remnant. Such a mass must be biopsied and demonstrated to be histologically benign prior to randomization or, if malignant, must be surgically removed with clear margins.
  • Patients in whom the margins of the resected specimen are involved with invasive tumor or DCIS.

Who cannot join

None listed.

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites

  • Providence Cancer Center

    Anchorage, Alaska, 99508

  • Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham

    Birmingham, Alabama, 35294

  • Blumenthal Cancer Center at Carolinas Medical Center

    Charlotte, North Carolina, 28232-2861

  • Altru Cancer Center at Altru Hospital

    Grand Forks, North Dakota, 58201

  • CCOP - Northern New Jersey

    Hackensack, New Jersey, 07601

  • Community Oncology Group at Cleveland Clinic Cancer Center

    Independence, Ohio, 44131

  • Lucille P. Markey Cancer Center at University of Kentucky

    Lexington, Kentucky, 40536-0093

  • Methodist Estabrook Cancer Center

    Omaha, Nebraska, 68114

  • Chestnut Hill Healthcare Cancer Center

    Philadelphia, Pennsylvania, 19118

  • South Shore Hospital

    South Weymouth, Massachusetts, 02190

  • Robert and Carol Weissman Cancer Center at Martin Memorial

    Stuart, Florida, 34994

  • Madigan Army Medical Center - Tacoma

    Tacoma, Washington, 98431

Other trials in United States

About this study

Official title: A Phase III, Adjuvant Trial Comparing Three Chemotherapy Regimens in Women With Node-Positive Breast Cancer: Docetaxel/Doxorubicin/Cyclophosphamide (TAC); Dose-Dense (DD) Doxorubicin/Cyclophosphamide Followed By DD Paclitaxel (DD AC→P); DD AC Followed By DD Paclitaxel Plus Gemcitabine (DD AC→PG)

RATIONALE: Drugs used in chemotherapy, such as docetaxel, doxorubicin , cyclophosphamide, paclitaxel, and gemcitabine work in different ways to stop tumor cells from dividing so they stop growing or die. Giving combination chemotherapy after surgery may kill any remaining tumor cells.

PURPOSE: This randomized phase III trial is studying three different combination chemotherapy regimens and comparing how well they work in treating women who have undergone surgery for node-positive breast cancer.

Read the detailed description

OBJECTIVES:

Primary

  • Compare disease-free survival in women with node-positive breast cancer treated with 3 different adjuvant chemotherapy regimens comprising dose-dense doxorubicin, cyclophosphamide, paclitaxel, and gemcitabine vs docetaxel, doxorubicin, and cyclophosphamide vs dose-dense doxorubicin, cyclophosphamide, and paclitaxel.

Secondary

  • Compare overall survival, recurrence-free interval, and distant recurrence-free interval, in patients treated with these regimens.
  • Compare the toxic effects of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to number of positive lymph nodes (1-3 vs 4-9 vs ≥ 10), hormone receptor status (estrogen receptor [ER]- and progesterone receptor [PgR]- negative vs ER- and/or PgR-positive), type of prior surgery and planned radiotherapy (lumpectomy and local radiotherapy [RT] without regional RT vs lumpectomy and local RT with regional RT vs mastectomy without RT vs mastectomy with local or regional RT). Patients are randomized to 1 of 3 treatment arms.

  • Group 1: Patients receive doxorubicin IV over 15 minutes, cyclophosphamide IV over 30 minutes, and docetaxel IV over 1 hour on day 1. Treatment repeats every 21 days for 6 courses.
  • Group 2: Patients receive AC chemotherapy comprising doxorubicin IV over 15 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 14 days for 4 courses. Beginning 14 days after the last dose of AC, patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 4 courses.
  • Group 3: Patients receive AC chemotherapy as in Group 2. Beginning 14 days after the last dose of AC, patients receive paclitaxel as in Group 2 and gemcitabine IV over 30-60 minutes on day 1. Treatment repeats every 14 days for 4 courses.

In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Beginning 3-12 weeks after the last dose of chemotherapy, patients with ER-positive and/or PgR-positive tumors receive hormonal therapy.

Beginning no sooner than 3 weeks after the last dose of chemotherapy, patients treated with lumpectomy undergo whole-breast radiotherapy. Patients treated with mastectomy may undergo chest wall and/or regional nodal radiotherapy.

Patients are followed every 6 months for 5 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 4,800 patients will be accrued for this study within 4 years.

Conditions
Breast Cancer
Keywords
stage II breast cancer, stage IIIA breast cancer, stage IIIC breast cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Also called C

    Group 1: cyclophosphamide 500 mg/m2 IV every 21 days for 6 cycles

    Group 2 and Group 3: cyclophosphamide 600 mg/m2 IV every 14 days for 4 cycles

  • DocetaxelDrug

    Also called Taxotere, T

    75 mg/m2 IV every 21 days for 6 cycles

  • GemcitabineDrug

    Also called Gemzar, G

    2000 mg/m2 IV every 14 days for 4 cycles

  • PaclitaxelDrug

    Also called Taxol, P

    175 mg/m2 IV every 14 days for 4 cycles

  • DoxorubicinDrug

    Also called A, Adriamycin

    Group 1: 50 mg/m2 IV every 21 days for 6 cycles

    Group 2 and Group 3: 60 mg/m2 IV every 14 days for 4 cycles

Study groups in NCT00093795
Study groupRoleWhat they receive
Group 1: TAC X 6Active comparatorDoxorubicin, cyclophosphamide, and docetaxel.
Receives: Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Doxorubicin
Group 2: AC X 4 then P X 4Active comparatorDoxorubicin, cyclophosphamide, and paclitaxel
Receives: Drug: Cyclophosphamide; Drug: Paclitaxel; Drug: Doxorubicin
Group 3: AC X 4 then PG X 4ExperimentalDoxorubicin, cyclophosphamide, paclitaxel and gemcitabine
Receives: Drug: Cyclophosphamide; Drug: Gemcitabine; Drug: Paclitaxel; Drug: Doxorubicin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease-free Survival: Any Recurrence, Contralateral Breast Cancer, Second Primary Cancer, Death From Any Cause Prior to Recurrence or Second Primary Cancer

    The percentage of patients alive and cancer-free.

    Measured: 5 years

Secondary outcomes (4)

  1. Overall Survival

    Percentage of participants alive at 5 years

    Measured: 5 years

  2. Recurrence-free Interval: Time to First Local, Regional, or Distant Recurrence

    Percentage of patients recurrence-free (no first local, regional, or distant recurrence)

    Measured: 5 years

  3. Distant Recurrence-free Interval: the Time to Distant Disease Recurrence Only

    Percentage of patients distant recurrence-free (no distant disease recurrence only)

    Measured: 5 years

  4. Toxicity

    Percentage of patients who ever experienced grade 2 or higher toxicities.

    Measured: 30 days after the last dose of study therapy (about 7 months after study entry)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Oct 2004 (estimated)
  2. Study startOct 2004
  3. Primary completionMar 2012
  4. Study completionJun 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
4,894 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00093795
Sponsor's protocol ID
NSABP B-38
Other IDs
U10CA012027
Status last verified
Dec 2017
First submitted
6 Oct 2004
Last updated
11 Jan 2018
Data monitoring committee
Yes

Publications

  • Swain SM, Tang G, Geyer CE Jr, Rastogi P, Atkins JN, Donnellan PP, Fehrenbacher L, Azar CA, Robidoux A, Polikoff JA, Brufsky AM, Biggs DD, Levine EA, Zapas JL, Provencher L, Northfelt DW, Paik S, Costantino JP, Mamounas EP, Wolmark N. Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B-38 trial. J Clin Oncol. 2013 Sep 10;31(26):3197-204. doi: 10.1200/JCO.2012.48.1275. Epub 2013 Aug 12.

    PubMed 23940225

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cyclophosphamide, Docetaxel and Gemcitabine in people with Breast Cancer, run by NSABP Foundation Inc at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 67 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease-free Survival: Any Recurrence, Contralateral Breast Cancer, Second Primary Cancer, Death From Any Cause Prior to Recurrence or Second Primary Cancer (time frame: 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00093795, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2018.

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