A Prospective, Multicenter, Open-label 12 Week Neoadjuvant Phase II Trial Optimizing Taxane Therapy in Elderly Patients With Low Response

Study Overview
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Brief Summary
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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.

Official Title
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A Prospective, Multicenter, Open-label 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.

Conditions
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Early Primary Breast Cancer

Intervention / Treatment
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* Drug: Myocet
* Drug: Cyclophosphamide
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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General Inclusion Criteria for ADAPT: Female patients, age at diagnosis 18 years and above (consider patients at 70 years and above for ADAPT Elderly) Candidate for chemotherapy on the basis of conventional criteria Histologically confirmed unilateral primary invasive carcinoma of the breast Clinical T1 - T4a-c All clinical N (cN) No clinical evidence for distant metastasis (M0) Known HR status and HER2 status (local pathology) Tumor block available for central pathology review Performance Status ECOG <= 1 or KI >= 80% 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 The patient must be accessible for treatment and follow-up Patients must qualify for neoadjuvant treatment LVEF > 50%; LVEF within normal limits of each institution measured by echocardiography and normal ECG (within 42 days prior to chemotherapy) Laboratory requirements : Leucocytes ≥ 3.5 x 109/L Platelets ≥ 100 x 109/L Hemoglobin ≥ 10 g/dL Total bilirubin ≤ 1 x ULN ASAT (SGOT) and ALAT (SGPT) ≤ 2.5 x UNL Creatinine ≤ 175 µmol/L (2 mg/dl) Additional inclusion criteria ADAPT Elderly: ≥ 70 years old Charlson scale ≤ 2 HR+/HER2- disease: if RS and sequential testing are available N0-1/RS 12-25/poor response or N0-1/RS ≥26 All G3 with Ki-67 ≥40% in tumors >1cm All N2 All TN All subtypes General Exclusion Criteria for ADAPT: Known hypersensitivity reaction to the compounds or incorporated substances Prior malignancy with a disease-free survival of < 10 years, except curatively treated basalioma of the skin, pTis of the cervix uteri Non-operable breast cancer including inflammatory breast cancer Previous or concurrent treatment with cytotoxic agents for any reason after consultation with the sponsor 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) Male breast cancer Sequential breast cancer Reasons indicating risk of poor compliance Patient not able to consent Additional Exclusion Criteria ADAPT Elderly: Known polyneuropathy ≥ grade 2 Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study Inadequate organ function (e.g. hepatic impairment, pulmonary disease, etc.) 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) Severe dyspnea Pneumonitis Abnormal blood values: Thrombocytopenia > CTCAE grade 1 Increases in ALT/AST > CTCAE grade 1 Hypokalaemia > CTCAE grade 1 Neutropenia > CTCAE grade 1 Anaemia > CTCAE grade 1

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Mycet/Cyclophosphamid<br>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<br> <br> * Other names: Doxorubicin;Drug: Cyclophosphamide<br> <br> |
| Active Comparator: Myocet/Cyclophosphamide/Paclitaxel<br>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<br> <br> * Other names: Doxorubicin;Drug: Cyclophosphamide<br> <br> Drug: Paclitaxel<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, elderly