Condition category
Cancer
Date applied
20/12/2005
Date assigned
20/12/2005
Last edited
01/05/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr S.C. Linn

ORCID ID

Contact details

Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital
Departments of Molecular Biology and Medical Oncology
Plesmanlaan 121
Amsterdam
1066 CX
Netherlands
+31 (0)20 5122951
s.linn@nki.nl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Acronym

MATADOR, BOOG 2005-02, CKTO 2004-04

Study hypothesis

Current study hypothesis as of 29/04/2013:
To define gene expression profiles that can predict a disease-free survival (DFS) advantage for either dose dense therapy, or docetaxel-containing chemotherapy.

Previous study hypothesis until 29/04/2013:
With microarray analysis of primary breast cancers of patients who participate in this study one can identify gene expression profiles that can predict a disease-free survival advantage for either dose dense therapy, docetaxel, and/or 6 versus 4 courses of chemotherapy.

Please note that as of 29/04/2013, the following changes were made to the trial record:
1. The anticipated end date for this trial was updated from 30/09/2008 to 19/11/2012
2. The target number of participants was updated from 1200 to 600

Ethics approval

Netherlands Cancer Institute, 15th March 2004, ref: EV04-87

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Not Specified

Patient information sheet

Condition

Breast cancer

Intervention

Current interventions as of 29/04/2013:
Randomization to one of the treatment arms (6 cycles TAC or AC dd)

ACdd:
doxorubicin 60 mg/m2 i.v. bolus and cyclophosphamide 600 mg/m2 i.v. bolus on day 1 every 2 weeks.
TAC:
Doxorubicin 50 mg/m² as an i.v. bolus on day 1, followed by cyclophosphamide 500 mg/m2 as i.v. bolus and, after 1 hour, docetaxel 75 mg/m² as 1 hour i.v. infusion on day 1 every 3 weeks.
Both Arms:
- prophylactic pegfilgrastim 6 mg s.c. given 1 day after completion of administration of each chemotherapy cycle;
- Radiotherapy, if indicated;
- Endocrine treatment for at least 5 years, (according to the most recent Dutch national guidelines)starting 1 to 6 weeks after radiotherapy or 3 to 6 weeks after chemotherapy for patients with positive estrogen and/or progesterone receptors.

HER2 positive patients
For HER2 positive patients we recommend to treat these patients outside the context of this study. Only in case of an increased risk of cardiotoxicity, the HERA study schedule is an alternative, in which case patients could participate in the MATADOR study.
Both Arms:
For HER2 positive patients with increased risk of cardiotoxicity, who are going to receive trastuzumab according to the schedule of the HERA study, trastuzumab should be given for 52 weeks, and should start within 7 weeks from day 1 of the last chemotherapy cycle or within 6 weeks from the end of adjuvant radiotherapy, whichever is last.

Previous interventions until 29/04/2013:
2 randomizations:
1. To one of the treatment arms (TAC or AC dd)
2. To 4 or 6 courses of chemotherapy (second randomization only open for patients with 1-3 positive axillary lymph nodes)

AC dd: doxorubicin 60 mg/m2 iv bolus and cyclophosphamide 600 mg/m2 iv bolus on day 1 every 2 weeks.
TAC: Docetaxel 75 mg/m2 1 hour i.v. infusion on day 1 in combination with doxorubicin 50 mg/m2 i.v. bolus and cyclophosphamide 500 mg/m2 i.v. bolus on day 1 every 3 weeks.

Both Arms:
1. Prophylactic pegfilgrastim 6 mg sc given 1 day after completion of administration of each chemotherapy cycle
2. Radiotherapy, if indicated
3. Endocrine treatment for 5 years, starting 1 to 6 weeks after radiotherapy or 3 to 6 weeks after chemotherapy for patients with positive estrogen and/or progesterone receptors.

Intervention type

Other

Phase

Phase III

Drug names

Primary outcome measures

Current primary outcomes as of 29/04/2013:
To define gene expression profiles that can predict a disease-free survival (DFS) advantage for either dose dense therapy, or docetaxel—containing chemotherapy.

Previous primary outcomes until 29/04/2013:
To define gene expression profiles that can predict a disease-free survival advantage for either dose dense therapy, docetaxel, and/or 6 versus 4 courses of chemotherapy.

Secondary outcome measures

Current secondary outcome measures as of 29/04/2013:
Is docetaxel-doxorubicin-cyclophosphamide (TAC) better than doxorubicin-cyclophosphamide dose-dense (AC dd) concerning DFS, RFS, breast cancer specific survival and all cause survival?
Objectives of optional side studies:
1. To determine whether the proteomic profile of patients, with primary breast cancer, relates to patient demographic characteristics, tumor stage, tumor biologic characteristics or tumor genetic (micro-array) profile
2. To identify a proteomic pattern that positively or negatively predicts relapse according to the genetic profile of the primary tumor (micro-array analysis) in each treatment arm
3. To identify a proteomic pattern in follow-up serum samples that can predict for relapse

Previous secondary outcome measures until 29/04/2013:
1. Is TAC better than AC dd regarding disease free survival and overall survival?
2. Are 6 courses better than 4 regarding disease free survival and overall survival?

Objectives of optional side studies
1.To determine whether the proteomic profile of patients, with primary breast cancer, relates to patient demographic characteristics, tumor stage, tumor biologic characteristics or tumor genetic (micro-array) profile
2.To identify a proteomic pattern that positively or negatively predicts relapse according to the genetic profile of the primary tumor (micro-array analysis) in each treatment arm
3.To identify a proteomic pattern in follow-up serum samples that can predict for relapse

Overall trial start date

01/10/2004

Overall trial end date

19/11/2012

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 29/04/2013:
1. Women with pT1-T3, pN0-3b, M0 adenocarcinoma of the breast (TNM classification 2002). Women with a macrometastasis in the sentinel node, who did not receive an axillary dissection (pN1(sn)), are only eligible if radiotherapy of the axilla is included in the treatment plan (for instance experimental arm AMAROS study);
2. Known HER2 and estrogen receptor status.
3. Frozen tumor tissue available (or tumor tissue sent in RNAlater to NKI-AVL).
4. primary surgery (defined as date of last surgical intervention) < 6 weeks before randomisation, or radiotherapy < 5 weeks before randomisation.
5. Good performance status (WHO < 1)
6. normal hematology, normal renal and liver function tests (see below).
7. no history of heart failure.
8. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures during study treatment (chemotherapy and hormonal therapy).
9. no conditions that may compromise follow-up.
10. informed consent.
11. At least 18 years old and able to undergo intensive chemotherapy (in the study of Martin et al. employing the TAC regimen (1d) age < 65 years was required).
12. Laboratory requirements: (within 14 days prior to registration)
12.1. Hematology:
12.1.1. Neutrophils ≥ 1.5 109/L;
12.1.2. Platelets ≥ 100 109/L;
12.1.3. Hemoglobin ≥6.0 mmol/L;
12.2. Hepatic function:
12.2.1. Total bilirubin ≤ 16 umol/L;
12.2.2. ASAT (SGOT) and ALAT (SGPT) ≤ 1.5 UNL;
12.2.3. Alkaline phosphatase ≤ 2.5 UNL;
12.3. Renal function:
12.3.1. Creatinine ≤ 120 µmol/L;
12.3.2. If limit values, the calculated creatinine clearance should be ≥ 60 mL/min.

Previous inclusion criteria until 29/04/2013:
1. Women with pT0-T3, pN 1-3b, M0 adenocarcinoma of the breast (TNM classification 2002). Women with a macrometastasis in the sentinel node, who did not receive an axillary dissection (pN1(sn)), are only eligible if radiotherapy of the axilla is included in the treatment plan (for instance experimental arm AMAROS study).
2. Frozen tumor tissue available (or tumor tissue sent in RNAlater to NKI-AVL)
3. Primary surgery <6 weeks before randomisation, or radiotherapy <5 weeks before randomisation
4. Good performance status; WHO <1
5. Normal hematology, normal renal and liver function tests (see below)
6. No history of heart failure
7. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures during study treatment (chemotherapy and hormonal therapy)
8. No conditions that may compromise follow-up
9. Written Informed consent
10. Able to undergo intensive chemotherapy (in the study of Nabholtz (1) age <65 years was required)
11. Laboratory requirements: (within 14 days prior to registration)
Hematology:
i. Neutrophils >1.5 x 10^9/l
ii. Platelets >100 x 10^9/l
iii. Hemoglobin >6.0 mmol/l
Hepatic function:
i. Total bilirubin <16 µmol/L
ii. ASAT (SGOT) and ALAT (SGPT) <1.5 UNL
iii. Alkaline phosphatase <2.5 UNL
Renal function:
i. Creatinine <120 µmol/l
ii. If limit values, the calculated creatinine clearance should be >60 ml/min

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

600

Participant exclusion criteria

Current exclusion criteria as of 29/04/2013:
1. Prior systemic anticancer therapy for any cancer (immunotherapy, hormonal therapy, chemotherapy)
2. Prior radiation therapy for breast cancer
3. HER2 positive breast cancer (except for patients who are going to be treated according to HERA study (1c)
4. Pregnant, or lactating patients
5. Pre-existing motor or sensory neurotoxicity of a severity > grade 2 by NCI criteria
6. Other serious illness or medical condition:
6.1. Congestive heart failure or unstable angina pectoris, previous history of myocardial infarction within 1 year from study entry, uncontrolled hypertension or high-risk uncontrolled arrhythmias
6.2. History of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent
6.3. Active uncontrolled infection
7. Past history of invasive breast cancer or past or current history of neoplasm other than breast carcinoma, except for:
7.1. Curatively treated non-melanoma skin cancer
7.2. In situ carcinoma of the cervix
7.3. Ipsilateral ductal carcinoma in-situ (DCIS) of the breast
7.4. Lobular carcinoma in-situ (LCIS) of the breast
8. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry
9. Male patients

Previous exclusion criteria until 29/04/2013:
1. Prior systemic anticancer therapy for any cancer (immunotherapy, hormonal therapy, chemotherapy)
2. Prior radiation therapy for breast cancer
3. Pregnant, or lactating patients
4. Pre-existing motor or sensory neurotoxicity of a severity > grade 2 by NCI criteria
5. Other serious illness or medical condition:
5.1 Congestive heart failure or unstable angina pectoris, previous history of myocardial infarction within 1 year from study entry, uncontrolled hypertension or high-risk uncontrolled arrhythmias
5.2 A history of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent
5.3 Active uncontrolled infection
6. Past or current history of neoplasm other than breast carcinoma, except for:
6.1 Curatively treated non-melanoma skin cancer
6.2 In situ carcinoma of the cervix, cipsilateral ductal carcinoma in-situ (DCIS) of the breast,
6.3 Llobular carcinoma in-situ (LCIS) of the breast
7. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry.
8. Male patients

Recruitment start date

01/10/2004

Recruitment end date

19/11/2012

Locations

Countries of recruitment

Netherlands

Trial participating centre

Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital
Amsterdam
1066 CX
Netherlands

Sponsor information

Organisation

Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (NKI AVL)

Sponsor details

Plesmanlaan 121
Amsterdam
1066 CX
Netherlands
+31 (0)20 5129111
y.rhemrev@nki.nl

Sponsor type

Not defined

Website

Funders

Funder type

Not defined

Funder name

Sanofi-Aventis, Amgen, Koningin Wilhelmina Fonds (KWF)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes