Cediranib + Olaparib for Ovarian and Breast Cancer

Recruiting at 13 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Untreated brain metastases, Uncontrolled hypertension, Recent myocardial infarction, others

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

Compensation: Varies

Number of Visits: 7

155 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing the combination of two drugs, cediranib maleate and olaparib, to treat patients with certain types of recurrent cancer. Cediranib maleate cuts off the blood supply to cancer cells, while olaparib stops them from repairing their DNA. The trial aims to find the best dose and see if the combination works better than using olaparib by itself. Combining cediranib, which cuts off the blood supply to cancer cells, with olaparib, which stops cancer cells from repairing their DNA, may help patients live longer without their cancer getting worse.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take certain medications that strongly affect liver enzymes (CYP3A4). You should discuss your current medications with the trial team to see if any adjustments are needed.

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

Research shows that the combination of Cediranib and Olaparib improved progression-free survival (the time during and after treatment that a patient lives with the disease without it getting worse) in women with recurrent platinum-sensitive ovarian cancer compared to 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 patients with ovarian and breast cancer, showing manageable side effects in early trials. These studies suggest that while the treatment has some toxicities, they are generally manageable, indicating a level of safety for human use. ^{1 2 3 4 6}

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

The combination of Cediranib and Olaparib is unique because it combines an anti-angiogenic drug (Cediranib) that blocks blood vessel growth with a PARP inhibitor (Olaparib) that prevents cancer cells from repairing their DNA, potentially improving progression-free survival in ovarian cancer compared to using Olaparib alone. ^{1 2 3 5 7}

Research Team

Joyce Liu, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults with recurrent ovarian, fallopian tube, peritoneal cancer or triple-negative breast cancer. Participants must have had platinum-based chemotherapy (for ovarian cancer), be able to monitor their blood pressure daily, and not have used certain other treatments before. They should be in good health otherwise, with a life expectancy over 6 months and no severe uncontrolled conditions.

Inclusion Criteria

Participants in the Phase II part of the trial must have a way to measure their disease according to specific guidelines.

Your total bilirubin level is within 1.5 times the normal limit at the hospital.

My breast cancer returned after treatments with Adriamycin and taxane.

Exclusion Criteria

Participants may not be receiving any other investigational agents nor have participated in an investigational trial within the past 4 weeks

You have had allergic reactions to similar drugs as cediranib maleate or olaparib.

My blood pressure is well-controlled.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment Phase I

Patients receive cediranib maleate and olaparib to determine the maximum tolerated dose. Cycles repeat every 28 days.

28 days per cycle

Multiple visits for monitoring and dose adjustments

Treatment Phase II

Randomized treatment with either cediranib maleate and olaparib or olaparib alone. Cycles repeat every 28 days.

28 days per cycle

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Every 6 months for up to 3 years

Follow-up visits every 6 months

Treatment Details

Interventions

• Cediranib Maleate
• Olaparib

Trial Overview The study is testing the effectiveness of combining Cediranib Maleate and Olaparib versus using Olaparib alone in treating specific recurrent cancers. It aims to find the best dose with manageable side effects and see if this combination can better prevent cancer growth by targeting both abnormal cell proliferation and the tumor's blood supply.

Participant Groups

Group I: Arm I (cediranib maleate and olaparib) Experimental Treatment 8 Interventions

Patients receive cediranib maleate PO QD and olaparib PO BID on days 1-28. Courses 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 on the trial. Patients may also optionally undergo a tissue biopsy on the trial.

Group II: Arm II (olaparib) Active Control 7 Interventions

Patients receive olaparib PO BID on days 1-28. Courses 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 on the trial. Patients may also optionally undergo a tissue biopsy on the trial.

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]

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]

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]

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

Overall survival and updated progression-free survival outcomes in a randomized phase II study of combination cediranib and olaparib versus olaparib in relapsed platinum-sensitive ovarian cancer. [2023]