Unresectable locally advanced or metastatic triple-negative breast cancer MedDRA version: 20.1 Level: LLT Classification code 10006212 Term: Breast carcinoma recurrent System Organ Class: 100000004864 MedDRA version: 20.1 Level: LLT Classification code 10006215 Term: Breast carcinoma stage III System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10006216 Term: Breast carcinoma stage IV System Organ Class: 100000004864
Conditions
Interventions
Product Name: Ceralasertib
Product Code: [AZD6738]
Pharmaceutical Form: Tablet
INN or Proposed INN: Ceralasertib
CAS Number: 1352226-88-0
Current Sponsor code: Non applicabile
Concentration unit: mg m
Sponsors
IFOM - Istituto FIRC di Oncologia Molecolare - Milano
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Metastatic TNBC patients, chemotherapy naïve therapy for metastatic treatment and whose tumor have relapsed from treatment with curative intent for early disease, which must include ICI and chemotherapy as part of radical locoregional therapy; 2. Documented disease progression (e.g., with biopsy sample, pathology or imaging report) since the last treatment in early setting with curative intent (neo/adjuvant regimen); 3. ATRiBRAVE trial written informed consent; 4. Age =18 years old; 5. Ability to comply with the study protocol in the investigator’s judgment, including ability to swallow and retain oral medication; 6. Availability of a formalin-fixed, paraffin-embedded block (FFPE) containing primary tumor tissue or at least 10-20 unstained tumor slides; 7. Negative ER/PgR and HER2 status, confirmed in the most recent tumor sample (primary and/or metastatic); 8. Evaluable disease as defined by RECIST 1.1; 9. ECOG performance status 0-1; 10. Acceptable organ functions measured within 28 days prior to trial; 11. Negative pregnancy test and willingness to use effective contraceptive methods from screening to 90 days from the last dose of durvalumab. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 7
Exclusion criteria
Exclusion criteria: 1. Diagnosis of ataxia telangiectasia. 2. Any previous treatment with ATR inhibitors, or DNA-damage repair inhibitors. 3. An adequate washout period prior to the start of study for any anticancer therapy. 4. Second primary cancer, except: non-melanoma skin cancer, or solid tumours curatively treated with no evidence of disease for =3 years; 5. Active or prior documented autoimmune or inflammatory disorders; 6. Patients with confirmed COVID-19 infection by PCR test who have not made a full recovery; 7. Leptomeningeal disease or symptomatic untreated CNS metastatic disease or cord compression. Asymptomatic metastases are conditionally eligible; 8. Any unresolved toxicity NCI CTCAE Grade =2 from previous anticancer therapy with the exception of alopecia and vitiligo; 9. Any evidence of severe or uncontrolled organ or systemic disease; 10. Any other clinical condition that may render the patient at high risk from treatment complications
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This study will evaluate the efficacy of ceralasertib followed by durvalumab plus Nab-paclitaxel in patients with TNBC, whose tumor relapsed following treatment with curative intent for early disease, which must have included ICIs and chemotherapy as part of the radical locoregional therapy (either adjuvant, neoadjuvant or both).;Secondary Objective: This study will further evaluate the efficacy and safety of the study treatments.;Primary end point(s): The primary efficacy endpoint is the progression free survival (PFS). PFS is defined as the number of days between the first study treatment administration to the date of first documented disease progression, relapse or death from any cause.;Timepoint(s) of evaluation of this end point: At the first documented disease progression, relapse or death from any cause. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Disease Control Rate (DCR) defined as the percentage of subjects whose disease shrinks or remains stable at 12 weeks. DCR is the sum of the complete response (CR), partial response (PR) and stable disease (SD) rates; Clinical Benefit Rate (CBR) defined as the proportion of patients with no disease progression at 24 weeks; Duration of Response (DoR) defined as the time from the date of first documented confirmed response until date of documented progression per RECIST v1.1 or death due to any cause;; Overall Survival (OS) defined as the number of days between the first study treatment administration and death; Occurrence of Adverse Events (AEs), including treatment-related AEs and AEs of special interest; Overall Response Rate (ORR) according to RECIST v 1.1 criteria;Timepoint(s) of evaluation of this end point: 12 weeks from the start of the treatment; 24 weeks from the start of the treatment; At the first documented disease progression, relapse or death from any cause.; Death; During the whole study duration; During the whole study duration | — |
Countries
Italy
Contacts
Public ContactPrecision Oncology Lab
IFOM – Istituto Fondazione di Oncologia Molecolare ETS
Outcome results
None listed