Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma, Endometrioid

Carcinosarcoma

Mixed Tumor, Mullerian

Ovarian Cancer

Ovarian Epithelial Cancer

Malignant Mixed Mullerian Tumor

Antineoplastic Agents

All Drugs and Chemicals

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Women with relapsed ovarian (fallopian tube / primary peritoneal) and endometrial (uterus) clear cell carcinomas with loss of ARID1A expression treated with single agent AZD6738.

In second stage of trial, opening of this cohort depends on response rate in cohort 1A during first stage of trial.

Women with relapsed ovarian (fallopian tube / primary peritoneal) and endometrial (uterus) clear cell carcinomas with loss of ARID1A expression treated with AZD6738 in combination with olaparib.

Women with relapsed ovarian (fallopian tube / primary peritoneal) and endometrial (uterus) clear cell carcinomas with NO loss of ARID1A expression treated with AZD6738 in combination with olaparib.

Women with other rare relapsed gynaecological cancers (endometrioid ovarian carcinoma, endometrioid endometrial carcinoma, cervical adenocarcinoma, cervical squamous, ovarian carcinosarcoma and endometrial carcinosarcoma) irrespective of ARID1A status, treated with AZD6738 in combination with olaparib.

AZD6738

Christy Toms

Katie Wilkinson

Michelle Everard

Susana Banerjee

ATARI trial tests the ATR inhibitor drug AZD6738 and a PARP inhibitor drug olaparib in patients with relapsed gynecological cancers to assess the response in groups of patients selected based on their cancer cell subtype and the presence of an abnormality in ARID1A gene.

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."

The trial tests the ATR inhibitor drug AZD6738 and a PARP inhibitor drug olaparib to assess the response in groups of patients selected based on their cancer cell subtype and the presence of an abnormality in ARID1A.

The treatment groups are: 1A - Women with clear cell subtype with (ovarian/uterus) ARID1A loss treated with AZD6738. 1B - Women with clear cell subtype with (ovarian/uterus) ARID1A loss treated with AZD6738 + olaparib. 2 - Women with clear cell subtype (ovarian/uterus) with no ARID1A loss treated with AZD6738 and olaparib. 3 - Women with other rare gynaecological cancers (carcinosarcoma, cervical, endometrioid type) irrespective of ARID1A loss treated with AZD6738 and olaparib.

Open-label, multiple two-stage parallel cohorts

ATr Inhibitor in Combination With Olaparib in Gynaecological Cancers With ARId1A Loss or no Loss

ATARI: ATr Inhibitor in Combination With Olaparib in Gynaecological Cancers With ARId1A Loss

A patient will be said to have had an overall objective response if they have a complete/partial response as assessed radiologically according to RECIST 1.1 at any point during trial treatment. A second scan to confirm response will be taken ≥ 4 weeks after the first scan showing an objective response.

The proportion of patients experiencing complete or partial response, or stable disease lasting at least 16 weeks from start of treatment as assessed radiologically by RECIST version 1.1.

Length of maintained response, measured according to RECIST v1.1

Measured according to RECIST v1.1 or death. Time to last tumour assessment will be used if patient has not progressed or died, and PFS time for the patient will be considered censored. PFS will be used to calculate the proportion of patients alive and free of progression at 6 months.

Measured according to RECIST v 1.1 or clinical progression of disease. Time to last tumour assessment will be used if patient has not progressed, and the patient will be considered censored. If the patient has died without prior progression, the patient will be censored at the date of death. Death will not count as a TTP event.

Adverse events thought to be related to drug will be graded according to NCI-CTCAE version 5.0, and coded using MedDRA (current version). Any dose reductions and delays in administration of drug due to toxicity will also be collected.

Defined by the time from start of treatment until death

Spots Global Cancer Trial Database for clear cell ovarian carcinoma