Cediranib + Olaparib for Ovarian Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining two medications, olaparib (Lynparza) and cediranib (cediranib maleate), to treat ovarian, primary peritoneal, or fallopian tube cancer that has returned after initial improvement. These drugs block enzymes that aid cancer cell growth. The trial suits individuals with these specific cancers who have not yet tried similar drugs. Participants must have experienced cancer relapse after responding to treatments like chemotherapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research shows that combining cediranib maleate with olaparib offers a promising treatment for ovarian cancer. Previous studies found that this combination significantly delays cancer progression compared to olaparib alone. This treatment is not only effective but also generally well-tolerated by patients.

Other studies have shown that olaparib, when used as ongoing therapy, is usually safe and well-tolerated for certain types of ovarian cancer. Similarly, combining cediranib maleate with olaparib has been reported as safe and tolerable for treating similar conditions.

Overall, evidence suggests that using these two drugs together is relatively safe for treating recurrent ovarian cancer. However, like any treatment, side effects may occur, and individual experiences can vary. Discuss any concerns with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Cediranib Maleate and Olaparib for ovarian cancer because it offers a novel approach to treatment. Unlike standard chemotherapy options, which attack rapidly dividing cells broadly, Olaparib is a PARP inhibitor that specifically targets cancer cells with certain genetic defects, making it more precise. Cediranib enhances this effect by inhibiting blood vessel growth that tumors need to thrive. This dual-action strategy not only aims to attack the cancer more effectively but also potentially reduces the side effects typically associated with traditional chemotherapy.

What evidence suggests that this treatment might be an effective treatment for ovarian cancer?

Research shows that using cediranib and olaparib together can significantly benefit patients with recurrent ovarian cancer that responds to platinum-based treatments. In this trial, participants will receive both cediranib and olaparib. Studies indicate that this combination allows patients to live longer without their cancer worsening compared to using olaparib alone. Simply put, patients taking both drugs experience longer periods without cancer returning. Cediranib and olaparib block certain proteins that cancer cells need to grow, helping to stop tumor growth. These findings suggest that this drug combination could be a promising treatment for recurring ovarian cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

Joyce Liu, MD

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

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 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]

Citations

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

Cediranib and Olaparib Combination Compared ... - PubMed We assessed the efficacy of cediranib, olaparib, and cediranib/olaparib compared with standard-of-care chemotherapy (SOC) in platinum-resistant or platinum- ...

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. 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 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02446600

NCT02446600 | Testing the Use of A Single Drug (Olaparib ... 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 ...

5. 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 ...

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 ...

7. 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 ...