Gynecological Cancers > AZD6738

Ceralasertib + Olaparib/Durvalumab for Gynecological Cancers (ATARI Trial)

Recruiting in Palo Alto (17 mi)

+8 other locations

Overseen By Susana Banerjee

Age: 18+

Sex: Female

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Institute of Cancer Research, United Kingdom

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

ATARI trial tests the ATR inhibitor drug ceralasertib (AZD6738) alone and in combination with either a PARP inhibitor drug called olaparib, or an anti-PD-L1 immunotherapy called durvalumab (MEDI4736) in patients with relapsed gynaecological cancers to assess the response in groups of patients selected based on their cancer cell subtype and the presence of an abnormality in the ARID1A gene.

Is the drug Olaparib a promising treatment for gynecological cancers?

Yes, Olaparib is a promising drug for gynecological cancers, especially ovarian cancer. It has shown to improve survival rates and is considered a standard treatment for patients with certain genetic mutations.

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What safety data is available for the treatment with Ceralasertib and Olaparib/Durvalumab in gynecological cancers?

The provided research does not directly address the safety data for the combination of Ceralasertib (AZD6738) and Olaparib/Durvalumab. However, it includes safety evaluations of Olaparib in various settings: (1) The SOLO1 trial analyzed the timing, duration, and grade of common adverse events in patients using Olaparib as maintenance therapy for advanced ovarian cancer with a BRCA mutation. (2) A systematic review assessed the safety of Olaparib in recurrent platinum-sensitive ovarian cancer. (3) A multistudy analysis explored the safety of Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation. These studies provide insights into the safety profile of Olaparib, which is part of the treatment combination in question.

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What data supports the idea that Ceralasertib + Olaparib/Durvalumab for Gynecological Cancers is an effective treatment?

The available research shows that olaparib, one of the drugs in the combination, has been effective in treating ovarian cancer, especially in patients with certain genetic mutations. Studies have shown that olaparib can help patients live longer without the cancer getting worse. While the specific combination of Ceralasertib + Olaparib/Durvalumab isn't directly covered in the research, the effectiveness of olaparib in similar conditions suggests potential benefits. However, more specific data on this combination for gynecological cancers would be needed to fully support its effectiveness.

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Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop all current medications, but there are restrictions. You cannot take certain medications that affect CYP3A4 and CYP1A2 enzymes, and there are washout periods for some treatments, like 21 days for cytotoxic treatments and 42 days for immunotherapy. It's best to discuss your current medications with the trial team to see if they are allowed.

Eligibility Criteria

This trial is for women with certain types of gynecological cancers (like ovarian, endometrial clear cell, and others) that have worsened after treatment. They must have a specific gene abnormality (ARID1A), measurable disease by scans, and be in good physical condition with a life expectancy over 16 weeks.

Inclusion Criteria

My cancer is mostly clear cell type without serous features.

My cancer is confirmed as carcinosarcoma through a biopsy.

My cancer has grown since my last cancer treatment.

My physical ability has been stable or better for the last 2 weeks.

I can provide a tissue sample from my diagnosis or relapse for testing.

My cancer can be measured by scans and does not rely solely on CA125 levels.

Participant Groups

The ATARI trial is testing the effectiveness of ceralasertib alone or combined with olaparib or durvalumab on patients whose cancer cells show ARID1A loss. It aims to see how well these drugs work based on the patient's cancer subtype.

Group I: 5: ceralasertib (AZD6738) + durvalumab Experimental Treatment 2 Interventions

Women with endometrial cancers (serous, clear cell, endometroid, carcinosarcoma) with NO loss of ARID1A.

Group II: 4: ceralasertib (AZD6738) + durvalumab Experimental Treatment 2 Interventions

Women with endometrial cancers (serous, clear cell, endometroid, carcinosarcoma) with ARID1A loss.

Group III: 3: ceralasertib (AZD6738) + olaparib Experimental Treatment 2 Interventions

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.

Group IV: 2: ceralasertib (AZD6738) + olaparib Experimental Treatment 2 Interventions

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.

Group V: 1B: ceralasertib (AZD6738) + olaparib Experimental Treatment 2 Interventions

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.

Group VI: 1A: ceralasertib (AZD6738) Experimental Treatment 1 Intervention

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

Find A Clinic Near You

Research locations nearby Select from list below to view details:

The Ottawa Hospital Cancer Centre Ottawa, Canada

Princess Margaret Cancer Centre Toronto, Canada

University of Montreal Hospital Centre Montreal, Canada

Who is running the clinical trial?

Institute of Cancer Research, United Kingdom Lead Sponsor

Cancer Research UK Collaborator

AstraZeneca Industry Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Phase I/Ib study of olaparib and carboplatin in BRCA1 or BRCA2 mutation-associated breast or ovarian cancer with biomarker analyses. [2022] Olaparib has single-agent activity against breast/ovarian cancer (BrCa/OvCa) in germline BRCA1 or BRCA2 mutation carriers (gBRCAm). We hypothesized addition of olaparib to carboplatin can be administered safely and yield preliminary clinical activity.

2. England pubmed.ncbi.nlm.nih.gov

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. [2022] The PARP inhibitor olaparib (Lynparza™) demonstrates antitumor activity in women with relapsed ovarian cancer and a germline BRCA1/2 mutation (gBRCAm). Data from olaparib monotherapy trials were used to explore the treatment effect of olaparib in patients with gBRCAm ovarian cancer who had received multiple lines of prior chemotherapy.

3. England pubmed.ncbi.nlm.nih.gov

Olaparib for the treatment of BRCA-mutated advanced ovarian cancer. [2019] The pharmacology, clinical efficacy, safety, dosage and administration, and role in therapy of olaparib, a first-in-class treatment for advanced treatment-refractory ovarian cancer, are reviewed.

4. United States pubmed.ncbi.nlm.nih.gov

Clinical factors associated with prolonged response and survival under olaparib as maintenance therapy in BRCA mutated ovarian cancers. [2022] To investigate clinical factors associated with prolonged progression-free survival (PFS) and overall survival (OS) in relapsing epithelial ovarian cancer (EOC) patients with BRCA mutations and receiving olaparib as maintenance therapy in daily practice.

5. United States pubmed.ncbi.nlm.nih.gov

Olaparib Makes OS Gains in Ovarian Cancer. [2021] Olaparib has solidified its place as a standard maintenance therapy for patients with platinum-sensitive relapsed ovarian cancer who have BRCA mutations. In the phase III SOLO 2 trial, the drug extended overall survival by more than a year in these patients compared with a placebo.

6. United States pubmed.ncbi.nlm.nih.gov

Tolerability of maintenance olaparib in newly diagnosed patients with advanced ovarian cancer and a BRCA mutation in the randomized phase III SOLO1 trial. [2022] In the phase III SOLO1 trial (NCT01844986), maintenance olaparib provided a substantial progression-free survival benefit in patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation who were in response after platinum-based chemotherapy. We analyzed the timing, duration and grade of the most common hematologic and non-hematologic adverse events in SOLO1.

7. United States pubmed.ncbi.nlm.nih.gov

Randomized phase II trial of weekly paclitaxel vs. cediranib-olaparib (continuous or intermittent schedule) in platinum-resistant high-grade epithelial ovarian cancer. [2022] Previous findings showed that cediranib-olaparib increased PFS in women with recurrent platinum-sensitive ovarian cancer compared to olaparib alone.

8. United States pubmed.ncbi.nlm.nih.gov

Randomized CLIO/BGOG-ov10 trial of olaparib monotherapy versus physician's choice chemotherapy in relapsed ovarian cancer. [2022] Comparison of olaparib (OLA) monotherapy versus chemotherapy in patients with platinum-sensitive (PSOC) or platinum-resistant ovarian cancer (PROC).

9. Switzerland pubmed.ncbi.nlm.nih.gov

Systematic Review of Olaparib in the Treatment of Recurrent Platinum Sensitive Ovarian Cancer. [2022] To systematically evaluate the efficacy and safety of olaparib in the treatment of recurrent platinum-sensitive ovarian cancer.

10. United States pubmed.ncbi.nlm.nih.gov

Cediranib in Combination with Olaparib in Patients without a Germline BRCA1/2 Mutation and with Recurrent Platinum-Resistant Ovarian Cancer: Phase IIb CONCERTO Trial. [2023] The efficacy, safety, and tolerability of cediranib plus olaparib (cedi/ola) were investigated in patients with nongermline-BRCA-mutated (non-gBRCAm) platinum-resistant recurrent ovarian cancer.