Early primary breast cancer, hormone receptor positve or negative, HER2 positive or negative, any nodal status. MedDRA version: 21.1 Level: LLT Classification code 10006188 Term: Breast cancer female NOS System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Epirubicin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: EPIRUBICIN
CAS Number: 56420-45-2
Concentration unit: mg/m2 milligram(s)/square meter
Concentra
Sponsors
Westdeutsche Studiengruppe GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: General Inclusion Criteria: • Female patients, age at diagnosis 18 years and above (consider ADAPT Elderly for patients at 70 years and above) • Histologically confirmed unilateral primary invasive carcinoma of the breast • T1 - T4 (except inflammatory breast cancer) • All N • Patients should be candidates for adjuvant chemotherapy according to conventional prognostic factors • 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 = 80% • Negative pregnancy test (urine or serum) within 7 days prior to registration 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 chemotherapy (within 14 days prior to randomization): o Leucocytes >= 3.5 10^9/L o Platelets >= 100 10^9/L o Hemoglobin >= 10 g/dL o Total bilirubin 14%, cT2-4c, If G1 only if clinical tumor size >3 cm o If Clinical decision is based on AdjuvantOnline patients should derive more than 5% 10-year relapse-free survival benefit by use of chemotherapy (3rd generation anthracycline/taxane-based) additional to standard endocrine therapy (using clinical T and N status) Additional Inclusion Criteria ADAPT HR+/HER2- Part II To be eligible for the participation in the ADAPT HR+/HER2- trial part II (neo)adjuvant chemotherapy question) the patients have to meet one of the following inclusion criteria: More than 3 involved lymph nodes (c/pN2-3)* N0-1 and RS = 26* N0-1 and RS 12-25 with Ki-67post > 10% G3 with Ki-67 =40% in tumors >1cm* To be a candidate for chemotherapy treatment due to high clinical risk irrespective of induction treatment (e.g. by heterogeneous tumor, multifocal tumor etc.) *with or without prior endocrine “test” treatment Patients with tumors =cT2 and/or cN+ are strongly recommended to be treated by neoadjuvant chemotherapy Laboratory requirements for patients receiving chemotherapy (within 14 days prior to randomization): o Leucocytes >= 3.5 x 109/L o Neutrophils >1.5 x 109/L o Platelets >= 100 x 109/L o Hemoglobin >= 10 g/dL o Total bilirubin <= 1 x
Exclusion criteria
Exclusion criteria: General Exclusion Criteria: • Known hypersensitivity reaction to the compounds or incorporated substances • Prior malignancy with a disease-free survival of = 5 x UNL o ASAT and/or ALAT associated with AP > 2.5 UNL Additional Exclusion Criteria ADAPT HR+/HER2- • Patients with clinical low risk tumors, who are not treated by adjuvant chemotherapy in the daily practice (e.g. cT1, G1, cN0) Additional Exclusion Criteria ADAPT HR+/HER2- Part II • Known polyneuropathy = grade 2 • Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study • Uncompensated cardiac function • Inadequate organ function including: o Leucocytes = 5 x UNL o ASAT and/or ALAT > 2.5 x UNL
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The ADAPT trial aims at personalizing therapy in early breast cancer by integration of dynamic response data into clinical management and at sparing unnecessary therapies without compromising patient outcome. Primary objective ADAPT umbrella • Identification of a responder sub-population with intermediate and high risk, which due to therapy has outcome comparable to HR+/RS = 11;Secondary Objective: Secondary objectives • Relapse-free and overall survival in corresponding groups • Overall survival • Toxicity • Cost-effectiveness • distant disease-free survival (DDFS) • local and regional relapse-free survival (LRFS and RRFS) Further specific objectives are defined within the sub-protocols. Toxicity and cost efficacy are common endpoints of all sub-protocols. Toxicity and general health economic issues within the whole protocol will be analyzed, when results from the sub-protocols are available. Additional translational research questions occurring during the trial will be defined in sub-protocols.;Primary end point(s): As stated in the sub-protocols, primary endpoints for the individual sub-studies are specific to the patient groups considered: • HR+/HER2-: Five-year EFS • HR+/HER2+: pCR • TN: pCR • HR+/HER2+: pCR • Elderly: pCR In addition, for ADAPT umbrella, 5-year EFS will be a primary endpoint for comparisons involving all five substudies: Five-year EFS will be prospectively compared between two groups defined as follows: • ADAPT Umbrella Test Group comprising - Patients with intermediate risk (RS 12-25) with early good response (and no chemotherapy); - Patients with pCR in HR+/HER2+ disease; - Patients with pCR in HR+/HER2- disease; - Patients with pCR in TN disease - Patients with pCR within ELDERLY substudy • ADAPT Umbrella Control Group comprising - Low-risk HR+/HER2- (RS< 12, N0-1) patients ADAPT HR+/HER2- part I: Primary Endpoint: Prospective comparison of EFS in “intermediate-RS” N0-1 dynamic responders vs. “low-RS” N0-1 pa | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): In all sub-studies and for groups within the studies, the following secondary endpoints (defined below) will be prospectively evaluated: Overall survival Relapse free survival Distant disease-free survival Local and regional relapse-free survival (LRFS and RRFS) Quality of life Toxicity In the ADAPT Umbrella project, these endpoints will be utilized in analyses including • Translational research/prognostic factor analysis • Cost-effectiveness analysis • Comparisons with historical, evidence based outcome estimates (e.g., using Adjuvant Online) ADAPT HR+/HER2- part II secondary endpoints: • Interim safety • pCR rates in the neoadjuvant treatment of dose dense paclitaxel-EC vs. nab-paclitaxel-EC arms ADAPT HER2+/HR+ secondary endpoints: • will be analyzed in an exploratory manner ADAPT TN secondary endpoints: • The following secondary endpoints (defined below) will be prospectively evaluated: Overall survival Relapse free survival Distant disease-free survival Local/regional relapse-free survival Evaluation of proliferation/apoptosis changes as surrogate marker for 5 year EFS. Relation of survival to study arm. ADAPT Elderly secondary endpoints: Comparison of toxicity in the two arms (MC vs MC->pac) allows evaluating whether the presumed higher risk of toxicity in the taxane-containing arm may be outweighed by the higher response rate in poor responders.;Timepoint(s) of evaluation of this end point: HR+/HER2- run-in: An interim safety analysis is planned after recruitment of 120 patients in both study arms. In this protocol, time to event (EFS (currently iDFS), DCIS-DFS, RFS, DDFS, L(R)FS and OS) will be defined as follows: • For all analyses related to endocrine-only patients (HR+/HER2-), time-to-event endpoints will start at the date of registration of patients • For all analysis related to chemotherapy application, time-to-event endpoints will start at the date of registration for the trial • For all HER2+, HER2+/HR+ and TNB | — |
Countries
Germany
Contacts
Public ContactStudienzentrale
Westdeutsche Studiengruppe GmbH
Outcome results
None listed