ATR Inhibitor + PARP Inhibitor for Ovarian Cancer
(CAPRI Trial)
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial tests a new treatment combination for women with recurring ovarian cancer. Researchers aim to determine if combining AZD6738 (an ATR inhibitor) with Olaparib (a PARP inhibitor) is safe and effective in slowing or stopping cancer growth. The trial includes women whose ovarian cancer has returned and either responds to or resists platinum-based treatments. Participants should have previously responded to treatments like Olaparib or possess specific genetic characteristics, such as BRCA mutations, that influence cancer response. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group.
Will I have to stop taking my current medications?
The trial requires a washout period (time without taking certain medications) for some drugs. If you are taking strong or moderate CYP3A inhibitors, you need to stop them two weeks before starting the trial. If you are on strong or moderate CYP3A inducers, the washout period is three to five weeks, depending on the specific drug.
Is there any evidence suggesting that this trial's treatments are likely to be safe?
Research has shown that combining Olaparib and AZD6738 may help treat ovarian cancer. The FDA has already approved Olaparib for some cancers, and it is usually well-tolerated. In studies with patients who have high-grade serous ovarian cancer, this combination has demonstrated positive effects, such as stabilizing the disease or partially reducing it in several cases.
Early results suggest that the combination can be safe, although some patients might experience side effects. Common side effects for similar treatments include nausea, tiredness, and changes in blood cell counts. However, the trial is still studying the safety of this treatment.
As this study is in an early phase, researchers are still collecting safety information. Participants might help discover more about the treatment's safety and tolerability.12345Why are researchers excited about this trial's treatments?
Researchers are excited about the combination of olaparib and AZD6738 for ovarian cancer because it targets cancer cells in a unique way. Unlike standard treatments that primarily focus on platinum-based chemotherapy, this combination uses a PARP inhibitor (olaparib) and an ATR inhibitor (AZD6738) to attack cancer cells that have specific genetic mutations, like BRCA or HRD mutations. This approach is especially promising for patients who have become resistant to other PARP inhibitors, offering a potential new option for those who have limited treatment choices. Additionally, the study explores different dosing schedules, which could personalize treatment for better effectiveness and fewer side effects.
What evidence suggests that this trial's treatments could be effective for ovarian cancer?
Research has shown that combining the drugs Olaparib and AZD6738 may help treat ovarian cancer. In this trial, all participants will receive this combination, but dosing and patient criteria will vary across different cohorts. Studies have found that this combination can reduce cancer cell survival and lead to more tumor shrinkage in patients who did not respond to previous treatments. Patients with BRCA mutations or DNA repair issues seem to benefit the most from this treatment. This suggests that using both drugs together might be effective for those with recurring ovarian cancer, regardless of their response to platinum-based treatments. Although this combination is still under study, early results are promising for those with certain genetic mutations.13567
Who Is on the Research Team?
Fiona Simpkins, MD
Principal Investigator
University of Pennsylvania
Are You a Good Fit for This Trial?
Women over 18 with recurrent ovarian cancer, either platinum-sensitive or resistant, can join. They must have good kidney and liver function, a certain level of fitness (ECOG 0 or 1), and a life expectancy over six months. Participants need measurable disease by RECIST v1.1 standards and may require specific BRCA mutation statuses depending on the cohort they're in.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive the combination of AZD6738 and olaparib. Dosing schedules vary by cohort, with olaparib administered orally twice daily and AZD6738 once daily.
Follow-up
Participants are monitored for safety and effectiveness after treatment, including assessment of treatment-emergent adverse events and progression-free survival.
What Are the Treatments Tested in This Trial?
Interventions
- Olaparib and AZD6738
Trial Overview
The trial tests AZD6738 combined with Olaparib pills in women with recurrent ovarian cancer to check safety, tolerability, response rate to treatment, and time without disease progression. It includes different cohorts based on sensitivity to platinum-based chemotherapy.
How Is the Trial Designed?
5
Treatment groups
Experimental Treatment
Cohort D Part II: Patients with ovarian cancer who are PARP inhibitor (PARPi) resistant (patients who have progressed on a PARPi). Patients must be platinum-sensitive and have a germline or somatic BRCA mutation or an HRD mutation. Approximately 12 patients will be treated. All patients will receive the combination of AZD6738 and olaparib. Cohort D will take a lower dose of olaparib (100-200 mg daily for a 28-day cycle) and a higher dose of AZD6738 (160-320 mg daily for about 14 days). Three to five dosing schedules will be evaluated.
Cohort D Part I: Patients will be platinum sensitive/platinum resistant ovarian cancer. Patient may or may not have received prior PARPi and will be enrolled irrespective of their BRCA status. The number of subjects treated will depend on the number of dose levels explored with a minimum of 12 subjects up to 30 subjects. All patients will receive the combination of AZD6738 and olaparib. Cohort D will take a lower dose of olaparib (100-200 mg daily for a 28-day cycle) and a higher dose of AZD6738 (160-320 mg daily for about 14 days). Three to five dosing schedules will be evaluated.
Cohort C: PARP inhibitor (PARPi) resistant (subjects who have progressed on a PARPi), patients must be platinum-sensitive, and have a germline or somatic BRCA mutation or an HRD mutation. Approximately 12 subjects could be treated. All patients will receive the combination of AZD6738 and olaparib. Patients will be administered olaparib orally twice daily at 300 mg BD. Patients will be administered AZD6738 orally once daily at 160 mg on days 1 to 7. For ease of administration, the AZD6738 should be administered at the same time as one of the olaparib doses and thus with one glass of water.
Cohort B: Recurrent platinum-resistant ovarian cancer (progression less than or equal to 6 months of the last receipt), approximately 37 patients could be treated with an interim analysis after 12 subjects. All patients will receive the combination of AZD6738 and olaparib. Patients will be administered olaparib orally twice daily at 300 mg BD. Patients will be administered AZD6738 orally once daily at 160 mg on days 1 to 7. For ease of administration, the AZD6738 should be administered at the same time as one of the olaparib doses and thus with one glass of water.
Cohort A: Recurrent platinum-sensitive ovarian cancer (progression greater than 6 months from last receipt of platinum-based chemotherapy), approximately 37 patients could be treated with an interim analysis after 17 subjects. All patients will receive the combination of AZD6738 and olaparib. Patients will be administered olaparib orally twice daily at 300 mg BD. Patients will be administered AZD6738 orally once daily at 160 mg on days 1 to 7. For ease of administration, the AZD6738 should be administered at the same time as one of the olaparib doses and thus with one glass of water.
Find a Clinic Near You
Who Is Running the Clinical Trial?
University of Pennsylvania
Lead Sponsor
Myriad Genetics, Inc.
Industry Sponsor
AstraZeneca
Industry Sponsor
Sir Pascal Soriot
AstraZeneca
Chief Executive Officer since 2012
Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris
Dr. Cristian Massacesi
AstraZeneca
Chief Medical Officer since 2021
MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology
Pascal Soriot
AstraZeneca
Chief Executive Officer since 2012
Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris
Cristian Massacesi
AstraZeneca
Chief Medical Officer since 2021
MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology
Published Research Related to This Trial
Citations
Combination ATR and PARP Inhibitor (CAPRI) Trial With ...
This study will determine if using Olaparib in combination with AZD6738 is safe and tolerable and also determine the objective response rate and progression ...
Combination ATR and PARP Inhibitor (CAPRI) trial with ...
Investigational agent, AZD6738 will be given in combination with Olaparib to women with recurrent ovarian cancer (platinum-sensitive or platinum-resistant).
Combination ATR and PARP Inhibitor (CAPRI): A phase 2 ...
Further, we have shown that combination PARP and ATR inhibition decreased survival and increased cancer regressions in PARPi and platinum-resistant BRCA½ mutant ...
A phase 2 study of the olaparib and AZD6738, an ATM ...
This study aims to evaluate the efficacy of Olaparib and AZD6738 in treating advanced IDH1/2 mutated solid.
5.
clinicaltrial.be
clinicaltrial.be/en/details/69197?per_page=20&only_recruiting=0&only_eligible=0&only_active=0Combination ATR and PARP Inhibitor (CAPRI) Trial With ...
This study will determine if using Olaparib in combination with AZD6738 is safe and tolerable and also determine the objective response rate and ...
Ceralasertib/Olaparib is Active in Recurrent, Platinum- ...
Ceralasertib plus olaparib demonstrated clinical activity in platinum-sensitive, recurrent, high-grade serous ovarian cancer, regardless of HRD status.
7.
aacrjournals.org
aacrjournals.org/mct/article/18/12_Supplement/A080/240253/Abstract-A080-Olaparib-and-the-ATR-inhibitorAbstract A080: Olaparib and the ATR inhibitor AZD6738 in ...
Of 7 patients with HGSOC resistant to platinum and PARP inhibitors (1-3 prior agents), 1 achieved a PR ( -90%), 3 had a best response of SD with ...
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