Olaparib vs. Cediranib + Olaparib for Recurrent Ovarian Cancer

Not currently recruiting at 414 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, VEGF inhibitors

Disqualifiers: Untreated brain metastases, HIV, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 25

Duration: Approximately 10 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of two treatments: olaparib alone and a combination of cediranib (a drug that inhibits blood vessel growth) and olaparib, compared to standard chemotherapy for recurrent ovarian, fallopian tube, or primary peritoneal cancer that responds to platinum-based treatments. The trial aims to determine if these treatments can halt tumor growth by blocking enzymes or blood vessel growth needed by tumors. Suitable participants have experienced cancer recurrence after platinum-based chemotherapy and have a specific type of ovarian cancer with a BRCA mutation. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer treatments.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain medications that affect kidney function or are strong inhibitors or inducers of specific enzymes. It's best to discuss your current medications with the trial team to ensure they don't interfere with the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that olaparib can serve as a treatment option for certain cancers. In one study, 89 out of 196 patients taking olaparib lived for more than 1.5 years without cancer progression, indicating its effectiveness and general tolerability for a period of time.

When combined with cediranib maleate, studies indicate that olaparib can extend the time patients live without their cancer worsening. Specifically, patients experienced a median time of 17.7 months without cancer progression. This combination has been found safe and tolerable for many patients.

These findings suggest that both olaparib alone and in combination with cediranib maleate are generally safe. However, like all treatments, they may have some side effects. Discussing these with the trial team is important for those considering joining a study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Olaparib and Cediranib Maleate for recurrent ovarian cancer because this duo offers a novel approach compared to existing treatments. Unlike the standard platinum-based chemotherapy, which primarily targets rapidly dividing cells, Olaparib is a PARP inhibitor. It works by preventing cancer cells from repairing their DNA, leading to cell death. Cediranib Maleate, on the other hand, is an anti-angiogenic agent that inhibits the growth of new blood vessels that tumors need to thrive. By combining these two mechanisms, the treatment targets cancer more comprehensively, potentially improving outcomes for patients with recurrent ovarian cancer.

What evidence suggests that this trial's treatments could be effective for recurrent ovarian cancer?

This trial will compare the effects of olaparib alone versus the combination of olaparib and cediranib maleate for recurrent ovarian cancer. Studies have shown that olaparib can significantly slow the growth or return of ovarian cancer. For example, in one study, 89 out of 196 patients taking olaparib lived for over 19 months without their cancer worsening. Participants in this trial may receive either olaparib alone or in combination with cediranib. When combined with cediranib, olaparib has been found to extend the time patients live without their cancer worsening, doubling the duration of stability compared to olaparib alone. However, some research suggests that this combination might not always outperform traditional chemotherapy. The combination works by blocking the enzymes and blood supply that tumors need to grow. ^{1 6 7 8 9}

Who Is on the Research Team?

Joyce F Liu

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

Women aged 18+ with platinum-sensitive high-grade ovarian, fallopian tube, or primary peritoneal cancer that responded well to initial platinum-based therapy. Must not have used PARP inhibitors before, can manage daily blood pressure checks, and agree to use two forms of contraception. No recent chemotherapy/radiotherapy or investigational drugs within the past month.

Inclusion Criteria

I have not taken PARP inhibitors for my ovarian, peritoneal, or fallopian tube cancer.

I have a specific type of ovarian cancer and a positive test for BRCA mutation.

My cancer can be measured by scans or has a high CA125 level.

Exclusion Criteria

You have untreated brain metastases, certain allergies, or specific heart conditions.

I haven't had chemotherapy or radiotherapy in the last 4-6 weeks and have recovered from any side effects.

I have never taken PARP inhibitor medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either olaparib, the combination of cediranib and olaparib, or standard platinum-based chemotherapy

Approximately 10 months

Every 21-28 days, depending on regimen

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Every 3 months for 2 years, then every 6 months for 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Cediranib Maleate
• Olaparib

Trial Overview The trial compares the effectiveness of Olaparib alone or combined with Cediranib against standard platinum-based chemotherapy in treating recurrent cancers. It examines if these drugs can better inhibit tumor growth by blocking enzymes and blood vessel formation necessary for tumors.

How Is the Trial Designed?

Group I: Arm III (olaparib, cediranib maleate) Experimental Treatment 10 Interventions

Patients receive olaparib PO BID and cediranib maleate PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo CT or MRI as well as blood sample collection throughout the trial.

Group II: Arm II (olaparib) Experimental Treatment 9 Interventions

Patients receive olaparib PO BID. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA during screening. Patients also undergo CT or MRI as well as blood sample collection throughout the trial.

Group III: Arm I (platinum-based chemotherapy) Active Control 11 Interventions

See detailed description.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

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

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]

In a phase II study involving 13 women with recurrent platinum-sensitive ovarian cancer, the combination of olaparib and cediranib showed greater biological activity than olaparib alone, indicated by significant decreases in IL-8 levels and increases in circulating endothelial cells (CEC).

Changes in CEC and IL-8 levels on treatment day 3 were associated with longer progression-free survival, suggesting these biomarkers could help predict patient response to the combination therapy, although further validation is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CECs and IL-8 Have Prognostic and Predictive Utility in Patients with Recurrent Platinum-Sensitive Ovarian Cancer: Biomarker Correlates from the Randomized Phase-2 Trial of Olaparib and Cediranib Compared with Olaparib in Recurrent Platinum-Sensitive Ovarian Cancer. Lee, JM., Trepel, JB., Choyke, P., et al.[2020]

In a phase IIb trial involving 60 women with platinum-resistant recurrent ovarian cancer, the combination of cediranib and olaparib showed a modest objective response rate (ORR) of 15.3%, indicating some clinical activity in this heavily pretreated population.

The treatment was associated with significant safety concerns, as 73.3% of patients experienced grade ≥3 adverse events, highlighting the need for careful monitoring and further research into biomarkers that could predict treatment response.

NCBI (Pubmed)

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. Lee, JM., Moore, RG., Ghamande, S., et al.[2023]

In a study of 69 Croatian patients with BRCA1-2 mutated, platinum-sensitive recurrent ovarian cancer, olaparib maintenance therapy demonstrated a median progression-free survival of 21 months, confirming its efficacy in a real-world setting.

The treatment was generally safe, with only 3% of patients discontinuing due to toxicity, although 88% experienced some level of side effects, indicating that while effective, monitoring for adverse effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib Outcomes in Patients with BRCA 1-2 Mutated, Platinum-Sensitive, Recurrent Ovarian Cancer in Croatia: A Retrospective Noninterventional Study. Majić, A., Miše, BP., Matković, V., et al.[2020]

The combination of cediranib and olaparib was found to have significant hematologic toxicities, with 75% of patients experiencing grade 3 or higher side effects, including severe neutropenia and thrombocytopenia at the highest dose.

In terms of efficacy, the treatment showed a promising overall response rate of 44% in patients with recurrent ovarian cancer, while no clinical responses were observed in breast cancer patients, indicating that this combination may be more effective for ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1 trial of the poly(ADP-ribose) polymerase inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer. Liu, JF., Tolaney, SM., Birrer, M., et al.[2021]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6503628/

Overall survival and updated progression-free ... In this updated analysis, combination cediranib/olaparib significantly improved progression-free survival over olaparib (16.5 versus 8.2 months) in relapsed ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02502266

NCT02502266 | Testing the Combination of Cediranib and ... Cediranib maleate and olaparib may stop the growth of tumor cells by blocking enzymes needed for cell growth. Chemotherapy drugs work in different ways to stop ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01116648

NCT01116648 | Cediranib Maleate and Olaparib in ... Cediranib maleate may help keep cancer cells from growing by affecting their blood supply. Olaparib may stop cancer cells from growing abnormally. The ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39361946/

Cediranib and Olaparib Combination Compared ... - PubMed Median PFS was 3.4, 5.2, and 4 months with SOC, cediranib/olaparib, and cediranib, respectively, with a median follow-up duration of 42.2 months ...

5. gpm.amegroups.org gpm.amegroups.org/article/view/10249/html

Prognostic analysis of single-agent olaparib or combination ... platinum-based chemotherapy (17). Combination of olaparib/cediranib did not improve PFS compared with chemotherapy and resulted in reduced PROs.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01116648

NCT01116648 | Cediranib Maleate and Olaparib in ... Olaparib may stop cancer cells from growing abnormally. The combination of cediranib maleate and olaparib may be safe, tolerable and/or effective in treating ...

7. targetedonc.com targetedonc.com/view/olaparibcediranib-combination-leads-to-continued-pfs-improvement-in-ovarian-cancer

Olaparib/Cediranib Combination Leads to Continued PFS ... The primary analysis, which was performed on March 31, 2014 after 47 events occurred, demonstrated a median PFS of 17.7 months for the women ...

8. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2015-00651

Testing the Combination of Cediranib and Olaparib in ... It is not yet known whether giving cediranib maleate and olaparib together may cause more damage to cancer cells when compared to either drug alone or standard ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT02502266

NCT02502266 | Testing the Combination of Cediranib and ... This randomized phase II/III trial studies how well cediranib maleate and olaparib work when given together or separately, and compares them to standard ...