Adavosertib + Olaparib for Recurrent Ovarian Cancer

Recruiting at 1 trial location

Overseen By Sara Hull

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: PARP inhibitors

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Uncontrolled brain metastases, Cardiac diseases, Active infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 6 months

96 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires a 'washout' period (time without taking certain medications) for some treatments. You must stop any hormonal therapy directed at the tumor at least one week before joining the study, and other cancer treatments at least three weeks before. Herbal supplements and certain drugs affecting liver enzymes should be stopped two weeks before starting the study.

What data supports the effectiveness of the drug combination Adavosertib + Olaparib for treating recurrent ovarian cancer?

Research shows that Olaparib, one of the drugs in the combination, is effective as a maintenance therapy for ovarian cancer, especially in patients with BRCA mutations, by prolonging progression-free survival. Additionally, combining Olaparib with another drug, Cediranib, has been shown to increase progression-free survival in recurrent ovarian cancer compared to Olaparib alone. ^{1 2 3 4 5}

What safety data exists for Olaparib in treating ovarian cancer?

Olaparib (Lynparza) has been evaluated for safety in treating ovarian cancer, particularly in patients with BRCA mutations. It is generally considered safe for use, but like all medications, it may have side effects, which should be discussed with a healthcare provider. ^{1 2 5 6 7}

How does the drug combination of Adavosertib, Ceralasertib, and Olaparib differ from other treatments for recurrent ovarian cancer?

This drug combination is unique because it combines Adavosertib and Ceralasertib with Olaparib, a PARP inhibitor, which is already used for maintenance therapy in ovarian cancer. The combination may offer a novel approach by potentially enhancing the effectiveness of Olaparib through the addition of other agents that target different pathways involved in cancer cell survival. ^{1 2 5 8 9}

What is the purpose of this trial?

This phase II trial studies how well adavosertib with or without olaparib work in treating patients with ovarian, primary peritoneal, or fallopian tube cancer that has come back (recurrent). Adavosertib and olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Research Team

Shannon Westin

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with recurrent ovarian, primary peritoneal, or fallopian tube cancer who've seen their disease progress on PARP inhibitors. They should have a measurable lesion and be in relatively good health (ECOG score 0-1). Women must not be pregnant, breastfeeding, and agree to use contraception. People can't join if they have heart issues like long QT syndrome, uncontrolled brain metastases, severe reactions to study drugs or certain drug interactions.

Inclusion Criteria

Has read and understands the informed consent form (ICF) and has given written informed consent prior to any study procedures.

My ovarian, peritoneal, or fallopian tube cancer has returned and cannot be cured with available treatments.

At least one measurable lesion according to RECIST v1.1.

Exclusion Criteria

I have not had a blood transfusion in the last 4 months.

I do not have a serious infection or condition that would stop me from receiving the study treatment.

I cannot swallow pills or have a stomach condition that affects medication absorption.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive study drugs according to their assigned arm: adavosertib alone, olaparib with adavosertib, or ceralasertib with olaparib. Treatment cycles repeat every 21 days.

Up to 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up for 30 days and periodically afterwards.

30 days

Treatment Details

Interventions

• Adavosertib
• Ceralasertib
• Olaparib

Trial Overview The trial tests adavosertib alone or combined with olaparib in patients whose cancer has returned. These drugs may block enzymes that tumor cells need to grow. Participants are chosen for different treatment groups based on specific criteria and will receive the treatments to see which works better.

Participant Groups

Group I: Arm III (ceralasertib, olaparib) Experimental Treatment 2 Interventions

Patient receive ceralasertib tablets by PO BID each day on Days 1-14. You will also take olaparib tablets by PO BID each day on Days 1-28.

Group II: Arm II (olaparib, adavosertib) Experimental Treatment 2 Interventions

Patients receive olaparib PO BID on days 1-21 and adavosertib PO QD on days 1-3 and 8-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group III: Arm I (adavosertib) Active Control 1 Intervention

Patients receive adavosertib PO QD on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Olaparib is an effective oral treatment for patients with BRCA mutation-positive ovarian cancer, approved for maintenance therapy after platinum-based chemotherapy, showing good tolerability with common side effects like nausea, fatigue, and anemia being mild to moderate.

Long-term monitoring is recommended due to a low risk of serious hematological complications, such as anemia and myelodysplastic syndrome, ensuring patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of olaparib for treating ovarian cancer. Lheureux, S., Bowering, V., Karakasis, K., et al.[2015]

The OPINION study is evaluating the safety and efficacy of olaparib as a maintenance therapy for women with high-grade serous or endometrioid platinum-sensitive relapsed ovarian cancer who do not have BRCA mutations, involving patients who have undergone at least two prior lines of platinum-based chemotherapy.

The primary goal of the study is to assess progression-free survival, which will help determine how effective olaparib is in delaying cancer progression in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design. Poveda, AM., Davidson, R., Blakeley, C., et al.[2020]

In a study of 115 relapsing epithelial ovarian cancer patients with BRCA mutations receiving olaparib, the median progression-free survival (PFS) was 12.7 months and overall survival (OS) was 35.4 months after a median follow-up of 21 months.

Key factors associated with longer PFS and OS included a platinum-free interval of 12 months or more, achieving a complete or partial response to treatment, and normalization of CA-125 levels after the last platinum-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical factors associated with prolonged response and survival under olaparib as maintenance therapy in BRCA mutated ovarian cancers. Labidi-Galy, SI., de La Motte Rouge, T., Derbel, O., et al.[2022]

In the BAROCCO trial involving 123 patients with recurrent platinum-sensitive ovarian cancer, the combination of cediranib and olaparib did not show superior progression-free survival (PFS) compared to paclitaxel chemotherapy, with median PFS of 5.6 months for the continuous cediranib-olaparib group and 3.1 months for the control group.

Despite not outperforming chemotherapy, the cediranib-olaparib combination was associated with a lower rate of treatment discontinuation due to adverse events (5% in the intermittent arm) and offers a potential non-chemotherapy treatment option for heavily pretreated patients.

NCBI (Pubmed)

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. Colombo, N., Tomao, F., Benedetti Panici, P., et al.[2022]

Olaparib (OLA) monotherapy showed a similar overall objective response rate (ORR) compared to chemotherapy (CT) in patients with relapsed ovarian cancer, with ORR of 24.3% for OLA and 28.3% for CT, indicating comparable efficacy.

In patients with platinum-resistant ovarian cancer (PROC) who had received more than four prior lines of treatment, OLA demonstrated a higher ORR of 22.9% compared to 0% for CT, suggesting that OLA may be more effective in heavily pretreated cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized CLIO/BGOG-ov10 trial of olaparib monotherapy versus physician's choice chemotherapy in relapsed ovarian cancer. Vanderstichele, A., Loverix, L., Busschaert, P., et al.[2022]

Olaparib, a PARP inhibitor, showed a 36% objective response rate in women with relapsed ovarian cancer and a germline BRCA1/2 mutation, even after they had undergone multiple lines of chemotherapy, indicating its efficacy in this challenging patient population.

The median duration of response to olaparib was 7.4 months, and the safety profile was consistent across patients who had received three or more lines of prior chemotherapy, with similar rates of serious adverse events.

NCBI (Pubmed)

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. Matulonis, UA., Penson, RT., Domchek, SM., et al.[2022]

Olaparib significantly improves overall survival in patients with recurrent platinum-sensitive ovarian cancer, with a hazard ratio of 1.24 based on a meta-analysis of 7 randomized controlled trials involving 2406 patients.

However, the treatment is associated with a higher incidence of adverse events, particularly for grades 3 or higher, indicating that while olaparib is effective, it also carries a risk of significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review of Olaparib in the Treatment of Recurrent Platinum Sensitive Ovarian Cancer. Chen, Q., Li, X., Zhang, Z., et al.[2022]

Olaparib is an effective treatment for patients with platinum-sensitive, relapsed BRCA-mutated high-grade serous ovarian cancer, showing significant improvement in progression-free survival compared to placebo in a study of 265 patients.

The treatment is generally well tolerated, with most side effects being mild to moderate, although fatigue, anemia, and neutropenia were noted as more severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: a review of its use as maintenance therapy in patients with ovarian cancer. Frampton, JE.[2016]

Olaparib is an effective first-line maintenance treatment for adults with advanced ovarian cancer who have responded to platinum-based chemotherapy, significantly improving progression-free survival compared to placebo in phase III trials.

When combined with bevacizumab, olaparib further enhances treatment efficacy in patients with homologous recombination deficiency (HRD), but does not show benefits in HRD-negative tumors, indicating its targeted effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: A Review as First-Line Maintenance Therapy in Advanced Ovarian Cancer. Paik, J.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of olaparib for treating ovarian cancer. [2015]

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

Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design. [2020]

3. 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]

4. 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]

5. 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]

6. 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]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Systematic Review of Olaparib in the Treatment of Recurrent Platinum Sensitive Ovarian Cancer. [2022]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Olaparib: a review of its use as maintenance therapy in patients with ovarian cancer. [2016]

9. France pubmed.ncbi.nlm.nih.gov

Olaparib: A Review as First-Line Maintenance Therapy in Advanced Ovarian Cancer. [2022]