Neoadjuvant Doxorubicin/Cyclophosphamide Followed by Docetaxel (AC-Doc) Versus Dose-Dense Doxorubicin and Docetaxel (ADoc) in Breast Cancer

November 18, 2008 updated by: German Breast Group

A Randomized, Multicenter, Open Phase III Study Comparing a Dose-Intensified 8 Week Schedule of Adriamycin and Docetaxel (ADOC) With a Sequential 24 Week Schedule of Adriamycin/Cyclophosphamide Followed by Docetaxel (AC-DOC) Regimen as Preoperative Therapy in Patients With Operable Carcinoma of the Breast (T2-3 N0-2 M0)

The primary objective of this trial is to compare the rate of pathologically complete remissions achieved using a preoperative dose-intensified 8 week therapy consisting of adriamycin and docetaxel with a preoperative sequential 24 week regimen consisting of adriamycin/cyclophosphamide followed by docetaxel, in patients with operable carcinoma of the breast. Secondary aims are to assess disease-free and overall survival, the rate of complete and partial responses by palpation and imaging methods, the rate of breast-conserving operations, and the toxicity of the two chemotherapy regimens.

Women meeting the following criteria will be eligible for the study: those with operable breast cancer (T2-3 N0-2 M0), with the diagnosis histologically confirmed by biopsy, and measurable disease on mammography or sonography or breast MRI (the most appropriate method should be chosen by the investigator). After the patients have given written informed consent, they will be randomly assigned to the study treatments. Patients in group I will receive four cycles of combination chemotherapy consisting of adriamycin 50 mg/m2 (15 min i.v. infusion) and docetaxel 75 mg/m2 (1 h i.v. infusion) repeated every 14 days, followed by surgery 9-10 weeks after the start of therapy. Patients in group II will receive four cycles of adriamycin 60 mg/m2 (15 min i.v.) and cyclophosphamide 600 mg/m2 (1 h i.v.) every three weeks, followed by four cycles of docetaxel 100 mg/m2 (1 h i.v.) every three weeks. Surgery will be performed during week 25 or 26. Patients in both groups will additionally receive oral doses of tamoxifen 20 mg once daily for 5 years, starting on the first day of chemotherapy. Surgery will consist of removal of the remaining tumor (breast-conserving resection or mastectomy) and axillary dissection (Sentinel node biopsy is allowed if the patient is involved in a randomized trial. Radiotherapy is applicated according to standard proceedings of participating center. A second randomization for additional versus no additional postoperative chemotherapy is recommended in ypN+ disease. Patients with disease progression during preoperative therapy, chemotherapy can be stopped and surgery can be performed immediately.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

913

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
    • Hessen
      • Neu-Isenburg, Hessen, Germany, 06102
        • German Breast Group

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Pre-study screening performed according to section 7.1
  • Unilateral primary carcinoma of the breast, confirmed histologically by core or tru-cut biopsy. Fine-needle aspiration is not sufficient. Incisional biopsy is only allowed if less than 20% of the tumor is excised.
  • Two-dimensionally measurable (mammography, ultrasound, or MRI) breast tumor
  • Primary tumor >= 2 cm in largest diameter by either palpation, sonography or mammography, or breast MRI. In patients with multifocal or multicentric breast cancer, the largest lesion should be measured.
  • No evidence of distant metastases
  • Life expectancy of at least 10 years, disregarding the diagnosis of cancer.
  • Karnofsky index >= 70%.
  • Age 18 years or older.
  • Adequate hematological, renal, and hepatic function (WBC > 4000, platelets > 100 000, bilirubin, serum creatinine and transaminases within 1.5 × upper normal range).
  • Evidence of normal cardiac function (with or without medication) from the patient history and from electrocardiography. Normal function is confirmed by echocardiography or multiple gated acquisition (MUGA) scan.
  • Negative pregnancy test and appropriate nonhormonal contraception in fertile women. Intrauterine pessaries with progestogens are allowed.
  • Written informed consent and assumed compliance for therapy and follow up of the patients.
  • Consent of patient, pathologist and investigator to supply tumor material of biopsy and surgery for central pathologic evaluation and examination of predictive factors.

Exclusion Criteria:

  • Locally advanced (stage T4), bilateral, metastatic, or inflammatory breast cancer. If one of these conditions is suspected, it has to be excluded before enrollment into study.
  • Previous treatment for breast cancer, including surgery, radiation, cytotoxic, or endocrine treatments.
  • Previous malignancy other than breast cancer or noninvasive breast cancer if the disease-free interval is less than 10 years.
  • Previous cytotoxic treatment for any condition.
  • Preexisting neurotoxicity greater than grade II.
  • Active infection or other significant illness that could influence the tolerability of treatment.
  • Current treatment with sex hormones (treatment has to be discontinued before the start of systemic therapy).
  • Psychiatric illness or drug addiction that would preclude obtaining informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ADOC x 4 + Tam 20
Adriamycin will be given at a dose of 50 mg/m2 and docetaxel at a dose of 75 mg/m2 every 14 days for four cycles. Adriamycin will be administered as a short i.v. infusion over 15 minutes, followed immediately by a 1-hour infusion of docetaxel diluted in 250 mL NaCl. Tamoxifen 20 mg is given once daily for five years to all patients, starting with the first day of chemotherapy.
Drug: Adriamycin (Doxorubicin), Docetaxel, Tamoxifen
Adriamycin will be given at a dose 50 mg/m2 and docetaxel at a dose of 75 mg/m2 every 14 days for four cycles.Tamoxifen 20 mg is given once daily for five years to all patients, starting with the first day of chemotherapy.
Experimental: AC x 4 - Doc x 4 + Tam 20
Adriamycin will be given at a dose of 60 mg/m2 and cyclophosphamide at a dose of 600 mg/m2 every 21 days for four cycles. Thereafter, docetaxel at a dose of 100 mg/m2 is given every 21 days for four cycles. Tamoxifen 20 mg is given once daily for five years to all patients, starting with the first day of chemotherapy
Drug: Adriamycin (Doxorubicin), Docetaxel, Tamoxifen, Cyclophosphamid
Adriamycin will be given at a dose of 60 mg/m2 and cyclophosphamide at a dose of 600 mg/m2 every 21 days for four cycles. Thereafter, docetaxel at a dose of 100 mg/m2 is given every 21 days for four cycles. Tamoxifen 20 mg is given once daily for five years to all patients, starting with the first day of chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Pathological locoregional complete tumor response (pCR) between both arms
Time Frame: 3 years
3 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Survival Local tumor response by palpation (cRR=cCR+cPR) Local tumor response by best imaging method (iRR=iCR+iPR) Response of axillary lymphnodes (NR) Breast conservation therapy (BCT) Toxicity
Time Frame: 3 years
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

German Breast Group

Collaborators

German Adjuvant Breast Cancer Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (Actual)

September 1, 2001

Study Registration Dates

First Submitted

November 17, 2008

First Submitted That Met QC Criteria

November 18, 2008

First Posted (Estimate)

November 19, 2008

Study Record Updates

Last Update Posted (Estimate)

November 19, 2008

Last Update Submitted That Met QC Criteria

November 18, 2008

Last Verified

November 1, 2008

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Gepar-Duo

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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