ER negative and HER2 negative Early Breast Cancer or BRCA 1 or 2 germline mutated Early Breast Cancer MedDRA version: 20.0 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: olaparib
Product Code: AZD 2281 (KU-0059436)
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Olaparib
CAS Number: 763113-22-0
Current Sponsor code: AZD2281
Other descriptive
Sponsors
Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For the PARTNER trial: • Written informed consent • Aged between 16 and 70 • Histologically confirmed invasive breast cancer • Clinical stage T1-4 N0-2 (tumour or metastatic node diameter > 10mm) • Confirmed ER-negative and HER2-negative or • Germline BRCA mutation positive, irrespective of hormone status but HER2 negative. • Performance Status 0-1 For the PARTNERING pathway: • Previous inclusion and treatment within PARTNER trial • Written informed consent (PARTNERING consent) • Performance Status 0-1 at registration into PARTNERING • Availability of an end of chemotherapy biopsy after cycle 6 and prior cycle 7 of PARTNER treatment • Histologically confirmed residual invasive breast cancer at biopsy performed after Cycle 6 of PARTNER therapy • Availability of TILs assessment in baseline biopsy prior Cycle 1 AND post Cycle 6 of PARTNER therapy is required • Body weight >30kg • Adequate bone marrow, hepatic, and renal function Are the trial subjects under 18? yes Number of subjects for this age range: 1 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 506 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: For the PARTNER trial: • T0 tumour in absence of axillary node > 10mm • TNBC with a non-basal phenotype and over-expressing Androgen Receptor • Not suitable for neoadjuvant chemotherapy • Distant metastases apparent prior to randomisation • Prior history of invasive breast cancer within the last 5 years • Previous PARP inhibitor use or any previous chemotherapy or targeted agent • Any previous chemotherapy or agent used for the treatment of cancer within the last 5 years For the PARTNERING pathway: • Rapidly progressive disease during PARTNER neoadjuvant treatment • Tumour cellularity less than 10% in biopsy performed after Cycle 6 of PARTNER therapy. • Not suitable for treatment with new agents • Persistent AEs from prior anti-cancer therapy =Grade 3
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of the PARTNER trial is to establish if the addition of Olaparib to neoadjuvant platinum-based chemotherapy for Triple negative breast cancer (TNBC) and/or germline mutated BRCA1/2 positive (gBRCA) breast cancer is safe and improves response to treatment as defined by pathological Complete Response (pCR) at surgery. The main objective of the PARTNERING pathway is to establish if the addition of further new agents: - Olaparib an PARP (Polyadenosine 5’diphosphoribose polymerisation) inhibitor, - AZD6738 an ATR (Ataxia telangiectasia mutated and rad3-related) inhibitor and - Durvalumab an PDL-1 (Programmed death-ligand 1) inhibitor improves response to treatment in those patients who have not achieved it after initial PARTNER trial therapy. ;Secondary Objective: The secondary research questions/objectives for the PARTNER trial are: Does the addition of olaparib: - Improve clinical outcomes (relapse free survival, overall survival ...) - Change the frequency/severity of toxicities experienced - Adversely affect Quality of life. Can we identify or validate pharmacogenetic and pharmacogenomic markers that can be correlated with outcomes (pCR and RFS) in patients randomised to receive olaparib with chemotherapy compared with those who receive just chemotherapy. Can we identify of markers for olaparib and chemotherapy response / resistance which are correlated with outcome. The secondary research questions for the PARTNERING pathway are: - Can the tumour content be correlated with the response to treatment. - Can the response to treatment be correlated with previous Olaparib treatment within the PARTNER trial. - Can the response to treatment be correlated with BRCA status. ;Primary end point(s): For the PARTNER trial: Stage 1: Primary outcome measure – safety of the addition of olaparib to three weekly carboplatin / weekly paclitaxel chemotherapy. Stage 2: Primary outcome measure – pCR in each of the two research arms. At the | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): For the PARTNER trial: • pCR and Residual Burden Disease at surgery assessed by central pathology review of the diagnosis and surgery slides. • Relapse Free Survival (RFS), calculated from date of randomisation to date of the first relapse or date of death from all causes, whichever occurs first. • Breast cancer specific survival (BCSS), calculated from date of randomisation to date of death from breast cancer. • Distant disease-free survival, calculated from date of randomisation to date of the first distant disease relapse or date of death from all causes, whichever occurs first. • Local recurrence-free survival, calculated from date of randomisation to date of the first local-recurrence or date of death from all causes, whichever occurs first. • Overall survival (OS), calculated from date of randomisation to date of death from all causes. • Time to second cancer (TTSC), calculated from the date of randomisation to the date of diagnosis of second cancer. • pCR in breast alone. • Residual Cancer Burden (RCB) I-III will be assessed by central pathology review. • Rate of breast conservation. • Radiological response after 4th and final cycles. • Treatment related toxicities. • Quality of life (sub-study, separate consent). No additional secondary end points for the PARTNERING pathway. ;Timepoint(s) of evaluation of this end point: Survival endpoints will be measured from the date of randomisation and will be reported for all deaths due to all causes. | — |
Countries
Australia, Israel, Netherlands, New Zealand, United Kingdom
Contacts
Public ContactCarrie Bayliss
Cambridge Clinical Trials Unit
Outcome results
None listed