Clinical trial NCT01815242: Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer - Triple Negative Breast Cancer
Official title: Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer - Triple Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: West German Study Group
Sponsor class: OTHER
Collaborators: name: Celgene
First posted: 2013-03-21
Enrollment: 336
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Comparison: pCR in nab-paclitaxel/carboplatin vs. nab-paclitaxel/gemcitabine
timeFrame: After 12 weeks of therapy
measure: Comparison: pCR in responders vs. non-responders
timeFrame: After 12 weeks of therapy
Secondary outcomes:
Other outcomes:
Locations:
city: Moenchengladbach
country: Germany
facility: Ev. Krankenhaus Bethesda Brustzentrum Niederrhein, Mönchengladbach, Germany
Study officials:
affiliation: Breast Center of the University of Munich (LMU), Universitätsfrauenklinik Großhadern, Munich, Germany
name: Nadia Harbeck, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Ev. Krankenhaus Bethesda Brustzentrum Niederrhein, Mönchengladbach, Germany
name: Ulrike Nitz, Prof. Dr.
role: STUDY_CHAIR
References:
citation: 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.
citation: Kolberg-Liedtke C, Feuerhake F, Garke M, Christgen M, Kates R, Grischke EM, Forstbauer H, Braun M, Warm M, Hackmann J, Uleer C, Aktas B, Schumacher C, Kuemmel S, Wuerstlein R, Graeser M, Nitz U, Kreipe H, Gluz O, Harbeck N. Impact of stromal tumor-infiltrating lymphocytes (sTILs) on response to neoadjuvant chemotherapy in triple-negative early breast cancer in the WSG-ADAPT TN trial. Breast Cancer Res. 2022 Sep 2;24(1):58. doi: 10.1186/s13058-022-01552-w.
citation: 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.