| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Her2/neu negative primary breast cancer, node positive disease or node negative disease with at least one other risk factor (tumor size >2cm, grade > or = 2, ER and PR negative, high uPA/PAI 1 level, RS>11 for ER/PR positive patients with 0-3 positive LN)
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| E.1.1.1 | Medical condition in easily understood language |
breast cancer trial for early diagnosed patients HER2 negative
Comparison of two chemotherapy regimes:
6xTC vs. 4xEC->4xDoc |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 19.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10057654 |
| E.1.2 | Term | Breast cancer female |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| Compare event-free survival in patients treated with either 6 cycles of Docetaxel / Cyclophosphamide chemotherapy or 4 cycles of EC followed by 4 cycles of Docetaxel as adjuvant treatment. |
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| E.2.2 | Secondary objectives of the trial |
Compare overall survival between the two arms
Compare the toxicity between the two arms |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
General Inclusion Criteria (Screening)
1. Female patients, age at diagnosis 18 - 75 years
2. Histological confirmed unilateral primary invasive carcinoma of the breast
3. Adequate surgical treatment with complete resection of the tumor (R0) and resection of 10 axillary nodes or SLN in clinically N0 patients
4. T1 - T4 (if operable, inflammatory breast cancer is excluded)
5. Her-2 non-over expressing tumor confirmed by IHC/FISH
6. Estrogen and/or progesterone receptor analysis performed on the primary tumor prior to randomization. Results must be known at the time of randomization
7. Node positive disease or node negative disease with at least one other risk factor (tumor size 2 cm, grade 2, ER and PR negative, high uPA//PAI-1 levels)
8. No evidence for distant metastasis (M0) after conventional staging
9. Performance Status ECOG 1 or KI 80 %
10. The patient must be accessible for treatment and follow-up
11. Written informed consent for shipping of tumor block for central pathology review and evaluation of Recurrence Score (HR positive) and participation in the planB trial prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements
HR positive patients must also meet all of the following clinical inclusion criteria:
12. Patient willingness to participate in adjuvant chemotherapy planB trial if RS > 11
13. Indication for chemotherapy given provided either > 4 involved lymph nodes or RS > 11 in 1-3 lymph nodes or N0 disease
Additional Inclusion Criteria (Randomisation)
All patients with HR negative breast cancer and patients with HR positive (ER and/or PR) tumors and node-positive disease with > 4 involved lymph nodes or 0-3 involved lymph nodes with RS > 11 will be randomized for chemotherapy question if they are meeting all of the following additional inclusion criteria prior to randomisation:
14. Laboratory requirements (within 21 days prior to randomization)
15. Negative pregnancy test (urine or serum) within 7 days prior to randomization in premenopausal patients
16. LVEF within normal limits of each institution measured by echocardiography or MUGA scan and normal ECG (within 42 days prior to randomization)
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| E.4 | Principal exclusion criteria |
General Exclusion Criteria (Screening)
1. HER2 over expression confirmed by IHC/FISH/CISH
2. Known hypersensitivity reaction to the compounds or incorporated substances
3. Known polyneuropathy grade 2
4. Severe and relevant comorbidity that would interact with the application of cytotoxic agents or the participation in the study including acute cystitis and ischuria and chronic kidney disease.
5. Prior malignancy with a disease-free survival of < 10 years, except curatively treated basalioma of the skin, pTis of the cervix uteri or ipsilateral ductal carcinoma in-situ (DCISpTis of the breast)
6. Non-operable breast cancer including inflammatory breast cancer
7. Previous or concurrent treatment with cytotoxic agents for any reason after consultation with the sponsor
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 breast cancer
10. Concurrent pregnancy; patients of childbearing potential must implement highly effective (less then 1% failure rate) non-hormonal contraceptive measures during the study treatment
11. Breast feeding woman
12. Sequential breast cancer
13. Lack of patient compliance
Additional Exclusion Criteria (Randomisation)
14. Inadequate organ function including
15. Time since axillary dissection > 42 days
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| E.5 End points |
| E.5.1 | Primary end point(s) |
·Unacceptable Toxicity
·Withdrawn Consent
·Relapse
·Second primary malignancy (with the exception of curatively treated non-melanoma skin cancer or in situ carcinoma of the cervix)
·Death
·Administration of other systemic cancer treatment other than study drug or endocrine therapy as per protocol
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 5 years after last patient out |
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| E.5.2 | Secondary end point(s) |
-comparison overal survival between the two arms
-comparison of toxicity between the two arms (safety evaluation)
-evaluate survival in the observation arm
-perform translational research regarding prognostic and predictive sectors |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| when the data of the first 100 patients per each treatment arm are evaluable |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 100 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 8 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 8 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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