Olaparib vs. Cediranib + Olaparib for Recurrent Ovarian Cancer

Recruiting at 401 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

579 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination of Cediranib and Olaparib for recurrent ovarian cancer?

Research shows that the combination of Cediranib and Olaparib can improve progression-free survival (the time during which the cancer does not get worse) in women with recurrent platinum-sensitive ovarian cancer compared to using Olaparib alone. This suggests that the combination may be more effective in delaying cancer progression. ^{1 2 3 4 5}

Is the combination of Cediranib and Olaparib safe for humans?

The combination of Cediranib and Olaparib has been studied in women with recurrent ovarian cancer and showed manageable side effects in early trials. Both drugs have been used in cancer treatments and have shown antitumor activity, with safety data indicating that the combination is generally tolerable. ^{1 4 5 6 7}

How is the drug combination of Cediranib and Olaparib unique for treating recurrent ovarian cancer?

The combination of Cediranib and Olaparib is unique because it combines an anti-angiogenic agent (Cediranib) that targets blood vessel growth with a PARP inhibitor (Olaparib) that helps prevent cancer cells from repairing themselves, potentially improving progression-free survival in women with recurrent ovarian cancer compared to using Olaparib alone. ^{1 4 5 8 9}

What is the purpose of this trial?

This phase III trial studies olaparib or cediranib maleate and olaparib to see how well they work compared with standard platinum-based chemotherapy in treating patients with platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer that has come back. Olaparib and cediranib maleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Cediranib maleate may stop the growth of ovarian, fallopian tube, or primary peritoneal cancer by blocking the growth of new blood vessels necessary for tumor growth. Drugs used in chemotherapy, such as carboplatin, paclitaxel, gemcitabine hydrochloride, and pegylated liposomal doxorubicin hydrochloride work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether olaparib or cediranib maleate and olaparib is more effective than standard platinum-based chemotherapy in treating patients with platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer.

Research Team

Joyce F Liu

Principal Investigator

NRG Oncology

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

References

1. 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]

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

Randomised phase II trial of olaparib, chemotherapy or olaparib and cediranib in patients with platinum-resistant ovarian cancer (OCTOVA): a study protocol. [2021]

3. Egypt 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. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. [2023]

5. 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]

6. England 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. [2021]

7. 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]

8. Switzerland 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. [2020]

9. 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]