Cediranib + Olaparib for Ovarian Cancer

Recruiting at 20 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: PARP inhibitors, VEGF pathway

Disqualifiers: Hypertension, Heart disease, Stroke, 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 32 months

70 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take certain medications that interact with the trial drugs, and herbal supplements are not allowed. It's best to discuss your current medications with the study team to ensure they are not prohibited.

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

Research shows that the combination of Cediranib and Olaparib is more effective in increasing 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. ^{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 was found to have manageable side effects, meaning the side effects were not too severe and could be controlled. ^{1 2 3 4 5}

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

The combination of Cediranib and Olaparib is unique because it combines a PARP inhibitor (Olaparib) with an anti-angiogenic agent (Cediranib) that targets VEGF receptors, potentially improving progression-free survival in women with recurrent ovarian cancer compared to using Olaparib alone. ^{1 2 3 4 5}

What is the purpose of this trial?

This study is evaluating whether a drug called olaparib and a drug called cediranib maleate work in treating patients with ovarian, primary peritoneal, or fallopian tube cancer that has come back (recurrent).

Research Team

Joyce Liu, MD

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Eligibility Criteria

This trial is for adults with recurrent ovarian, primary peritoneal, or fallopian tube cancer. Participants must have measurable disease and not have used PARP inhibitors before. They should be in good physical condition (ECOG <=2) and able to take oral medications. Those with controlled blood pressure, no recent chemotherapy or invasive cancers (with some exceptions), and no history of certain heart conditions can join.

Inclusion Criteria

My thyroid function is normal, with no symptoms of dysfunction.

I have high-grade ovarian, peritoneal, or fallopian tube cancer or a BRCA mutation.

You have low levels of protein in your urine on two separate tests, or a specific ratio of protein to creatinine in your urine.

Exclusion Criteria

I have not used PARP inhibitors or drugs affecting the VEGF pathway for my cancer.

I haven't had chemotherapy, radiation, or hormonal therapy for my cancer in the weeks before joining the study.

I am HIV-positive and not on combination antiretroviral therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olaparib orally twice daily and cediranib maleate once daily on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 32 months

Regular visits for biopsy, blood sample collection, MUGA or echocardiogram, and CT or MRI scans

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

30 days

Long-term follow-up

Participants are monitored for overall survival and other long-term outcomes

Up to 1 year

Treatment Details

Interventions

• Cediranib Maleate
• Olaparib

Trial Overview The study tests the effectiveness of combining Cediranib Maleate and Olaparib in treating patients whose ovarian cancer has returned after treatment. It examines if these drugs can block enzymes needed for tumor growth, using imaging techniques like CT scans and MRIs to measure results.

Participant Groups

Group I: Treatment (olaparib and cediranib maleate) Experimental Treatment 9 Interventions

Patients receive olaparib PO BID and cediranib maleate PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a biopsy of tumor, blood sample collection, MUGA or echocardiogram, and CT scan or MRI scan throughout the study.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

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 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]

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]

References

1. 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]

2. 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]

3. 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]

4. 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]

5. 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]