A Prospective, Multicenter, Open-label 12 Week Neoadjuvant Phase II Trial Optimizing Taxane Therapy in Elderly Patients With Low Response
Study Details
Study Description
Brief Summary
Comparison of pre-surgical Myocet/ Cyclophosphamide (MC) q3w followed by either MC or Paclitaxel - depending on early response assessment by ultrasound or by toxicity for elderly non frail primary breast cancer patients with increased risk of relapse.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Mycet/Cyclophosphamid 4 x Myocet 60 mg/m² q3w in combination with 4 x cyclophosphamide 600 mg/m² q3w depending on early response assessment by ultrasound or on toxicity profile. |
Drug: Myocet
Other Names:
Drug: Cyclophosphamide
|
| Active Comparator: Myocet/Cyclophosphamide/Paclitaxel 2 x Myocet 60 mg/m² q3w in combination with 2 x cyclophosphamide 600 mg/m² q3w followed by 6 x paclitaxel 80 mg/m² q1w depending on early response assessment by ultrasound or on toxicity profile. |
Drug: Myocet
Other Names:
Drug: Cyclophosphamide
Drug: Paclitaxel
|
Outcome Measures
Primary Outcome Measures
- Comparison of pCR rates in patients with early response and no severe toxicity (Group 1) and in other patients (Group 2). [After 5 years of follow-up.]
Secondary Outcome Measures
- Incidence of febrile neutropenia (FN) after 1 x MC in patients with primary prophylaxis (PP) vs. others. [After 5 years of follow-up.]
- Toxicity in the 4 x MC versus 2 x MC followed 6 x Pac arm as measured by adverse events. [After 5 years of follow-up.]
- Number of pCR in non-responders to MC. [After 5 years of follow-up.]
- G-CSF use in terms of primary or secondary prophylaxis per patient including occurence febrile neutropenia per patient per cycle [After 5 years of follow-up.]
Eligibility Criteria
Criteria
General Inclusion Criteria for ADAPT:
-
Female patients, age at diagnosis 18 years and above (consider patients at 70 years and above for ADAPT Elderly)
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Candidate for chemotherapy on the basis of conventional criteria
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Histologically confirmed unilateral primary invasive carcinoma of the breast
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Clinical T1 - T4a-c
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All clinical N (cN)
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No clinical evidence for distant metastasis (M0)
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Known HR status and HER2 status (local pathology)
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Tumor block available for central pathology review
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Performance Status ECOG <= 1 or KI >= 80%
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Written informed consent 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
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The patient must be accessible for treatment and follow-up
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Patients must qualify for neoadjuvant treatment
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LVEF > 50%; LVEF within normal limits of each institution measured by echocardiography and normal ECG (within 42 days prior to chemotherapy)
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Laboratory requirements :
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Leucocytes ≥ 3.5 x 109/L
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Platelets ≥ 100 x 109/L
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Hemoglobin ≥ 10 g/dL
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Total bilirubin ≤ 1 x ULN
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ASAT (SGOT) and ALAT (SGPT) ≤ 2.5 x UNL
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Creatinine ≤ 175 µmol/L (2 mg/dl)
Additional inclusion criteria ADAPT Elderly:
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≥ 70 years old
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Charlson scale ≤ 2
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HR+/HER2- disease: if RS and sequential testing are available N0-1/RS 12-25/poor response or N0-1/RS ≥26
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All G3 with Ki-67 ≥40% in tumors >1cm
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All N2
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All TN
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All subtypes
General Exclusion Criteria for ADAPT:
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Known hypersensitivity reaction to the compounds or incorporated substances
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Prior malignancy with a disease-free survival of < 10 years, except curatively treated basalioma of the skin, pTis of the cervix uteri
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Non-operable breast cancer including inflammatory breast cancer
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Previous or concurrent treatment with cytotoxic agents for any reason after consultation with the sponsor
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Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry (concurrent participation in non-interventional post authorization safety studies not influencing the primary study endpoints is allowed, e.g. WSG PROTROCA for evaluation of primary/secondary G-CSF prophylaxis)
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Male breast cancer
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Sequential breast cancer
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Reasons indicating risk of poor compliance
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Patient not able to consent
Additional Exclusion Criteria ADAPT Elderly:
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Known polyneuropathy ≥ grade 2
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Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study
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Inadequate organ function (e.g. hepatic impairment, pulmonary disease, etc.)
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Uncompensated cardiac function (current unstable ventricular arrhythmia requiring treatment, history of symptomatic CHF NYHA classes II-IV), history of myocardial infarction or unstable angina pectoris within 12 months of enrollment, history of severe hypertension, CAD - coronary artery disease)
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Severe dyspnea
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Pneumonitis
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Abnormal blood values:
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Thrombocytopenia > CTCAE grade 1
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Increases in ALT/AST > CTCAE grade 1
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Hypokalaemia > CTCAE grade 1
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Neutropenia > CTCAE grade 1
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Anaemia > CTCAE grade 1
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ev. Krankenhaus Bethesda Brustzentrum Niederrhein | Moenchengladbach | Germany | 41061 | |
| 2 | Breast Center of the University of Munich (LMU) Universitätsfrauenklinik Großhadern | Munich | Germany | 81337 |
Sponsors and Collaborators
- West German Study Group
- Teva Pharmaceuticals USA
Investigators
- Principal Investigator: Nadia Harbeck, Prof. Dr., Breast Center of the University of Munich (LMU) Universitätsfrauenklinik Großhadern, Munich, Germany
- Study Chair: Ulrike Nitz, Prof. Dr., Ev. Krankenhaus Bethesda Brustzentrum Niederrhein, Mönchengladbach, Germany
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- WSG-AM06 / ADAPT Elderly