ADAPT - Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer (ADAPT)

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

Trial for the optimization of risk assessment and therapy success prediction in patients with early breast cancer by the use of biomarkers in advance to therapy decision-making to personalize therapies.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Docetaxel; Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Paclitaxel

• Study Type: Interventional
• Enrollment (Estimated): 4936
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Germany
  • Bavaria
    • Munich, Bavaria, Germany, 81377
      • Breast Center of the University of Munich (LMU) Universitätsfrauenklinik Großhadern
  • NRW
    • Mönchengladbach, NRW, Germany, 41061
      • Ev. Krankenhaus Bethesda Brustzentrum Niederrhein

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 x 10^9/L
  • Platelets >= 100 x 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Anthracycline - Taxane; Study sites can choose between either Epirubicin (90mg/m²) Cyclophosphamide (600mg/m²) q3w OR Epirubicin (90mg/m²) Cyclophosphamide (600mg/m²) q2w for anthracycline treatment and between either 4 x Docetaxel (100mg/m²) q3w OR 12 x Paclitaxel (80mg/m²) q1w for taxane treatment.	Drug: Docetaxel; Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Paclitaxel
Experimental: Taxane - Anthracycline; Study sites can choose between either Epirubicin (90mg/m²) Cyclophosphamide (600mg/m²) q3w OR Epirubicin (90mg/m²) Cyclophosphamide (600mg/m²) q2w for anthracycline treatment and between either 4 x Docetaxel (100mg/m²) q3w OR 12 x Paclitaxel (80mg/m²) q1w for taxane treatment.	Drug: Docetaxel; Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Identification of a responder sub-population with intermediate and high risk, which due to therapy has outcome comparable to HR+/RS≤11	3 Years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	3 Years

Collaborators and Investigators

• Sponsor: West German Study Group
• 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

Publications and helpful links

General Publications

• Hofmann D, Nitz U, Gluz O, Kates RE, Schinkoethe T, Staib P, Harbeck N. WSG ADAPT - adjuvant dynamic marker-adjusted personalized therapy trial optimizing risk assessment and therapy response prediction in early breast cancer: study protocol for a prospective, multi-center, controlled, non-blinded, randomized, investigator initiated phase II/III trial. Trials. 2013 Aug 19;14:261. doi: 10.1186/1745-6215-14-261.
• Nitz UA, Gluz O, Kummel S, Christgen M, Braun M, Aktas B, Ludtke-Heckenkamp K, Forstbauer H, Grischke EM, Schumacher C, Darsow M, Krauss K, Nuding B, Thill M, Potenberg J, Uleer C, Warm M, Fischer HH, Malter W, Hauptmann M, Kates RE, Graser M, Wurstlein R, Shak S, Baehner F, Kreipe HH, Harbeck N. Endocrine Therapy Response and 21-Gene Expression Assay for Therapy Guidance in HR+/HER2- Early Breast Cancer. J Clin Oncol. 2022 Aug 10;40(23):2557-2567. doi: 10.1200/JCO.21.02759. Epub 2022 Apr 11.
• Graeser M, Schrading S, Gluz O, Strobel K, Herzog C, Umutlu L, Frydrychowicz A, Rjosk-Dendorfer D, Wurstlein R, Culemann R, Eulenburg C, Adams J, Nitzsche H, Prange A, Kummel S, Grischke EM, Forstbauer H, Braun M, Potenberg J, von Schumann R, Aktas B, Kolberg-Liedtke C, Harbeck N, Kuhl CK, Nitz U. Magnetic resonance imaging and ultrasound for prediction of residual tumor size in early breast cancer within the ADAPT subtrials. Breast Cancer Res. 2021 Mar 18;23(1):36. doi: 10.1186/s13058-021-01413-y.
• Nitz U, Gluz O, Kreipe HH, Christgen M, Kuemmel S, Baehner FL, Shak S, Aktas B, Braun M, Ludtke-Heckenkamp K, Forstbauer H, Grischke EM, Nuding B, Darsow M, Schumacher C, Krauss K, Malter W, Thill M, Warm M, Wuerstlein R, Kates RE, Harbeck N. The run-in phase of the prospective WSG-ADAPT HR+/HER2- trial demonstrates the feasibility of a study design combining static and dynamic biomarker assessments for individualized therapy in early breast cancer. Ther Adv Med Oncol. 2020 Nov 23;12:1758835920973130. doi: 10.1177/1758835920973130. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2012
• Primary Completion (Actual): September 1, 2019
• Study Completion (Actual): January 15, 2025

Study Registration Dates

• First Submitted: January 25, 2013
• First Submitted That Met QC Criteria: January 25, 2013
• First Posted (Estimated): January 30, 2013

Study Record Updates

• Last Update Posted (Actual): April 8, 2025
• Last Update Submitted That Met QC Criteria: April 7, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antibiotics, Antineoplastic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase Inhibitors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Docetaxel; Cyclophosphamide; Paclitaxel; Epirubicin
• Other Study ID Numbers: WSG-AM06 / ADAPT HR+/HER2-