Cediranib + Olaparib for Ovarian and Breast Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and assess the effectiveness of two drugs, cediranib and olaparib, in treating certain recurrent cancers, including ovarian and triple-negative breast cancer. Cediranib (cediranib maleate) may slow cancer growth by affecting blood supply, while olaparib (also known as Lynparza) targets abnormal cancer cell growth. Researchers seek to determine if these drugs are more effective together than olaparib alone. Individuals with recurrent ovarian, fallopian tube, or triple-negative breast cancer who have previously undergone chemotherapy might be suitable candidates for this trial. As a Phase 1 and Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

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.

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

Research is examining the safety and effectiveness of combining cediranib maleate and olaparib for treating certain recurring cancers, such as ovarian cancer. Studies suggest that this combination can be safe and manageable for patients. However, while these drugs together might help control cancer growth, researchers continue to monitor for possible side effects.

Olaparib alone has already received approval for some cancers and is generally well-tolerated. Research shows it can slow cancer progression, with most patients experiencing manageable side effects.

Overall, while both treatments show promise, clinical trials continue to better understand their safety when used together. Participants in these trials receive close monitoring to manage any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a new approach to fighting ovarian and breast cancer. Cediranib and olaparib are oral medications that work together to target cancer cells more effectively. Cediranib is a VEGF receptor inhibitor, which helps block the blood supply to tumors, potentially starving them. Olaparib, on the other hand, is a PARP inhibitor that interferes with the cancer cells' ability to repair their DNA, making them more vulnerable to damage. This combination could provide a more powerful option compared to traditional treatments like chemotherapy, which often have significant side effects and can harm healthy cells too.

What evidence suggests that this trial's treatments could be effective for recurrent ovarian, fallopian tube, peritoneal, or triple-negative breast cancer?

This trial will compare the combination of cediranib and olaparib with olaparib alone for patients with ovarian and breast cancer. Research has shown that using cediranib and olaparib together can help patients with relapsed platinum-sensitive ovarian cancer live longer without their cancer worsening, compared to using olaparib alone. Cediranib cuts off the blood supply tumors need to grow, while olaparib stops cancer cells from multiplying excessively. Early studies found that patients with ovarian and breast cancer can manage the side effects of this combination. These results suggest that using both drugs together might be more effective than using just olaparib. ^{1 2 3 5 6}

Who Is on the Research Team?

Joyce Liu, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

Citations

1. 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 ...

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

Overall survival and updated progression-free ... Combination cediranib/olaparib significantly extends PFS compared with olaparib alone in relapsed platinum-sensitive ovarian cancer. Subset analyses suggest ...

3. withpower.com withpower.com/trial/phase-2-adenocarcinoma-2-2010-16c2a

Cediranib + Olaparib for Ovarian and Breast Cancer The combination of Cediranib and Olaparib has been studied in patients with ovarian and breast cancer, showing manageable side effects in early trials. These ...

4. dana-farber.org dana-farber.org/clinical-trials/16-715

refractory ovarian, fallopian tube, or primary peritoneal ... This randomized phase II/III trial studies how well cediranib maleate and olaparib work when given together or separately, and compares them to standard ...

5. 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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6489675/

Efficacy and safety of olaparib maintenance therapy in ... Conclusion: This meta-analysis suggests that olaparib maintenance therapy is effective and well-tolerated for the patients with platinum-sensitive BRCA-mutated ...