German Preoperative Adriamycin Docetaxel Study

NCT ID: NCT00543829

Last Updated: 2007-10-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-04-30
• Study Completion Date: 1999-06-30

Brief Summary

The primary objective of this trial is to determine the rate of pathologically complete remissions following a preoperative dose-intensified therapy with doxorubicin and docetaxel with or without tamoxifen in patients with operable carcinoma of the breast. Secondary aims are to assess the rate of clinical complete and partial responses, of breast-conserving operations, and the toxicity of chemotherapy with and without tamoxifen.

Women meeting the following criteria will be eligible for the study: operable breast cancer (T³3cm N0-2 M0), histologically confirmed diagnosis by core-cut needle or incisional biopsy, and measurable disease by mammography or sonography or breast MRI (best appropriate method has to chosen by investigator). After the patients have given written informed consent, they will be randomised to the study treatments. All patients are scheduled to receive 4 cycles of combination chemotherapy consisting of doxorubicin 50 mg/m² (15-min i.v. infusion) and docetaxel 75 mg/m² (1-h i.v. infusion). The patients allocated to group I additionally receive oral doses of tamoxifen 30 mg once daily, starting on the first day of chemotherapy, while chemotherapy alone is administered to patients of group II. Cycles should be repeated every 14 days, followed by surgery 8 weeks after initiation of the trial. Surgery consists of removal of the remaining tumour (breastconserving resection or mastectomy) and axillary dissection. Patients with no response or even progression of the primary tumour can be treated to the discretion of the investigator but should be followed up according to protocol. If a partial or complete tumour response has been achieved, radiotherapy is given to the remaining breast in patients undergoing breast conserving therapy, and tamoxifen treatment is continued for a further 5 years.

Response will be assessed between the 4th cycle and surgery, using the best appropriate method. Clinical evaluation should be performed after each cycle. It is planned to recruite 200 patients during a period of 1 year.

Conditions

Breast Neoplasms

Keywords

breast cancer; doxorubicin; docetaxel; tamoxifen

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

4 cycles of doxorubicin and docetaxel with tamoxifen

Group Type: EXPERIMENTAL

doxorubicin, docetaxel, tamoxifen

Intervention Type: DRUG

Every 14 days to a total of 4 cycles of doxorubicin (50 mg/m², 15 minutes i.v. infusion) and docetaxel (75 mg/m², 1 hour i.v. infusion) with tamoxifen (30 mg tablet p.o. for 5 years post surgery)

2

4 cycles of doxorubicin and docetaxel without tamoxifen

Group Type: ACTIVE_COMPARATOR

doxorubicin, docetaxel

Intervention Type: DRUG

Every 14 days to a total of 4 cycles of doxorubicin (50 mg/m², 15 minutes i.v. infusion) and docetaxel (75 mg/m², 1 hour i.v. infusion)

Interventions

doxorubicin, docetaxel, tamoxifen

Every 14 days to a total of 4 cycles of doxorubicin (50 mg/m², 15 minutes i.v. infusion) and docetaxel (75 mg/m², 1 hour i.v. infusion) with tamoxifen (30 mg tablet p.o. for 5 years post surgery)

Intervention Type: DRUG

doxorubicin, docetaxel

Every 14 days to a total of 4 cycles of doxorubicin (50 mg/m², 15 minutes i.v. infusion) and docetaxel (75 mg/m², 1 hour i.v. infusion)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Unilateral primary carcinoma of the breast, confirmed histologically by core-cut needle or incisional biopsy. Fine needle aspiration is not sufficient.
• Bidimensionally measurable tumour, either by mammography or breast ultrasound or breast MRI
• Primary tumour >= 3 cm in largest diameter. In patients with multifocal or multicentric breast cancer the largest lesion should be measured.
• No evidence of distant metastases (as confirmed by chest x-ray, liver ultrasound and bone scintigraphy)
• Age >= 18 years and <= 70 years.
• Life expectancy at least 10 years, ignoring the diagnosis of cancer.
• Karnofsky index >=70%.
• Adequate haematologic, renal and hepatic function (WBC >4000, platelets >100000, bilirubin, serum creatinine and transaminases within the normal range).
• Anamnestic and electrocardiographic evidence of normal cardiac function, without or with medication. Normal cardiac function measured by echocardiography or MUGA-scan.
• Negative pregnancy test and appropriate non-hormonal contraception in fertile women.
• Written informed consent and presumed compliance of the patients.

Exclusion Criteria

• Locally advanced (stage T4), bilateral, metastatic, or inflammatory breast cancer (tethering or dimpling of the skin as well as nipple inversion may not easily be interpreted as skin infiltration). If one of these conditions is suspected it has to be excluded before enrollment onto study.
• Previous treatment for breast cancer, including surgery, radiation, cytotoxic or endocrine treatments. Surgical diagnostic procedures are allowed.
• Previous malignancy other than breast cancer or non-invasive breast lesions if the disease-free interval is less than 10 years.
• Previous cytotoxic treatment for any condition.
• Preexisting neurotoxicity greater than grade II (WHO).
• Active infection or other significant illness that could influence 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

GBG Forschungs GmbH

OTHER

Sponsor Role: lead

Principal Investigators

Manfred Kaufmann, MD

Role: PRINCIPAL_INVESTIGATOR

J. W. Goethe University, School of Medicine, Dep. of Gynecology and Obstetrics

References

von Minckwitz G, Sinn HP, Raab G, Loibl S, Blohmer JU, Eidtmann H, Hilfrich J, Merkle E, Jackisch C, Costa SD, Caputo A, Kaufmann M; German Breast Group. Clinical response after two cycles compared to HER2, Ki-67, p53, and bcl-2 in independently predicting a pathological complete response after preoperative chemotherapy in patients with operable carcinoma of the breast. Breast Cancer Res. 2008;10(2):R30. doi: 10.1186/bcr1989. Epub 2008 Apr 1.

Reference Type: DERIVED

PMID: 18380893 (View on PubMed)

Other Identifiers

Gepardo

Identifier Type: -

Identifier Source: org_study_id