Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer - Triple Negative Breast Cancer

Study Overview
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Brief Summary
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The trial will evaluate the optimal treatment with nab-paclitaxel in combination with either carboplatin or gemcitabine for patients with triple negative breast cancer.

Official Title
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Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer - Triple Negative Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: nab-Paclitaxel
* Drug: Gemcitabine
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Female patients, age at diagnosis 18 years and above (consider patients at 70 years and above for ADAPT Elderly) Histologically confirmed unilateral primary invasive carcinoma of the breast Clinical T1 - T4 (except inflammatory breast cancer) 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 % Negative pregnancy test (urine or serum) within 7 days prior to start of induction treatment in premenopausal patients 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 Additional Inclusion Criteria for patients receiving chemotherapy: Laboratory requirements for patients receiving neoadjuvant chemotherapy (within 14 days prior to induction treatment): Leucocytes >= 3.5 10^9/L Platelets >= 100 10^9/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) LVEF within normal limits of each institution measured by echocardiography and normal ECG (within 42 days prior to induction treatment) Exclusion Criteria: 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 or 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 interventional clinical trial with or without any investigational not marketed drug within 30 days prior to study entry Male breast cancer Concurrent pregnancy; patients of childbearing potential must implement a highly effective (less than 1% failure rate) non-hormonal contraceptive measures during the study treatment Breast feeding woman Sequential breast cancer Reasons indicating risk of poor compliance Patients not able to consent Additional Exclusion Criteria for patients receiving chemotherapy: Known polyneuropathy ≥ grade 2 Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study including acute cystitis and ischuria and chronic kidney disease Uncompensated cardiac function Inadequate organ function including: Leucocytes < 3.5 x 10^9/l Platelets < 100 x 10^9/l Bilirubin above normal limits Alkaline phosphatase > 5 x UNL ASAT and/or ALAT associated with AP > 2.5 x UNL

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>nab-Paclitaxel + gemcitabine | Drug: nab-Paclitaxel<br> <br> Drug: Gemcitabine<br> <br> |
| Experimental: Arm B<br>nab-Paclitaxel + carboplatin | Drug: nab-Paclitaxel<br> <br> Drug: Carboplatin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison: pCR in nab-paclitaxel/carboplatin vs. nab-paclitaxel/gemcitabine | pCR will be measured after 12 weeks of randomized treatment. | After 12 weeks of therapy | 
| Comparison: pCR in responders vs. non-responders | pCR will be measured after 12 weeks of randomized treatment. | After 12 weeks of therapy |