ATARI: ATr inhibitor in combination with olaparib in gynaecological cancers with ARId1A loss or no loss
Disease site: Relapsed gynaecological cancers
Treatment modality: Systemic targeted therapy, ATR inhibitor, PARP inhibitor
Status: Open to recruitment
ATARI is a multi-centre, open-label, multiple two-stage parallel cohorts phase II clinical trial for patients with relapsed gynaecological cancers, with ARID1A-deficient ('loss') and "no loss."
ATARI will evaluate activity of ATR inhibitor drug AZD6738 as a single agent and in combination with PARP inhibitor drug olaparib in cohorts stratified by ARID1A protein expression and gynaecological cancer cell subtype.
In the first stage of the ATARI trial, a total of thirty patients with relapsed gynaecological cancers will be recruited into three cohorts. Ten patients with ovarian clear cell or endometrial clear cell cancer and ARID1A loss will be allocated into cohort 1A and treated with single agent AZD6738. Ten patients with ovarian clear cell or endometrial clear cell cancer with no loss of ARID1A will be allocated into cohort 2 and treated with AZD6738 in combination with olaparib.
Ten patients with either ovarian endometrioid, endometrial endometrioid, cervical adenocarcinoma, cervical squamous, ovarian carcinosarcoma or endometrial carcinosarcoma, irrespective of ARID1A expression, will be allocated into cohort 3 and treated with AZD6738 in combination with olaparib.
Patients will be assessed by a CT scan every eight weeks to evaluate response to treatment as measured by RECIST 1.1 objective response rate. Treatment will continue in all cohorts until confirmation of disease progression, unacceptable toxicity, patient withdrawal of consent or investigator decision.
If ≤1 response is seen in patients receiving AZD6738 as a single agent in the first stage, cohort 1A will close and cohort 1B will open and patients with ovarian clear cell or endometrial clear cell cancer and ARID1A loss will be allocated into cohort 1B, where they will receive AZD6738 in combination with olaparib.
If > 1 response is seen in a cohort, the cohort will continue recruitment in the second stage of the trial, enrolling a further 29 patients.
Further information for potential participants
Patient Information Sheet Cohort 1a
Patient Information Sheet Cohort 1b
Patient Information Sheet Cohort 2
Patient Information Sheet Cohort 3
Patient Information Sheet Tissue Screening
Further information for healthcare professionals
Chief Investigator: Dr Susana Banerjee, The Royal Marsden NHS Foundation Trust
ICR-CTSU Scientific Lead: Professor Judith Bliss
Trial management contact: ATARIemail@example.com
Sponsor: The Institute of Cancer Research
Funding: AstraZeneca, The Lady Garden Foundation
Further information including recruitment progress is available on ClinicalTrials.gov
A lay summary in plain English is available from Cancer Research UK: To be confirmed
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