Cediranib + Olaparib for Cancer

Not currently recruiting at 17 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Untreated brain metastases, Cardiac arrhythmia, 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 43 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two drugs, cediranib (which may help cut off oxygen to tumors) and olaparib (also known as Lynparza, used to treat certain cancers), to determine if they can stop cancer cells from growing or spreading. It focuses on advanced solid tumors that cannot be surgically removed, including breast, lung, and pancreatic cancer. The trial targets individuals who have tried standard treatments but still have measurable disease. Cediranib might enhance the tumor's sensitivity to olaparib by cutting off its oxygen supply. For those with a solid tumor that has spread and who have not succeeded with other treatments, this trial might be suitable. As a Phase 2 trial, the research measures 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 does not specify if you need to stop your current medications, but it does exclude participants using strong inhibitors or inducers of CYP3A4 enzymes and those using certain herbal products or alternative medicines. It's best to discuss your current medications with the study team to see if they might interfere with the trial.

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

Research has shown that using cediranib maleate and olaparib together might be safe and manageable for treating certain cancers. Studies have found that this combination can help patients live longer without their cancer worsening compared to using olaparib alone.

Researchers are also investigating whether using both drugs together is more effective at damaging cancer cells than using them separately. One study suggested that olaparib, which can stop cancer cells from growing, works well with cediranib maleate. Together, they might help treat solid tumors that have spread or cannot be removed by surgery.

While this combination looks promising, it is important to consider any side effects and consult a healthcare professional before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for cancer?

Researchers are excited about the combination of Cediranib and Olaparib for cancer treatment because it offers a unique approach by combining two targeted therapies. Cediranib is an anti-angiogenic drug that blocks blood vessel growth in tumors, cutting off their nutrient supply, while Olaparib is a PARP inhibitor that interferes with cancer cell DNA repair, leading to cell death. This dual mechanism not only tackles cancer from two angles but also has the potential to overcome resistance seen with traditional therapies like chemotherapy and radiation. By combining these two drugs, there's hope for improved effectiveness, especially in hard-to-treat cancers, compared to the current standard treatments.

What evidence suggests that this treatment might be an effective treatment for advanced/metastatic cancer?

Research has shown that using cediranib maleate with olaparib can help patients live longer without their cancer worsening, particularly in cases of relapsed ovarian cancer. Cediranib cuts off the tumor's blood supply, enhancing the effectiveness of olaparib, which inhibits cancer cell growth. Studies have found that this combination delays cancer progression more effectively than olaparib alone. This trial will evaluate the combination's effectiveness and safety for other advanced or hard-to-treat cancers, such as breast, lung, and pancreatic cancers. The combination is considered safe and may offer hope for those with difficult-to-treat tumors. ^{1 2 3 5 6}

Who Is on the Research Team?

Joseph W. Kim, MD

Principal Investigator

Yale University Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with advanced or inoperable solid tumors, including breast, non-small cell lung, small cell lung, and pancreatic cancers. Participants must have had at least one standard treatment previously and be able to take oral medication. They should not be pregnant or breastfeeding and must use effective contraception. People with recent significant bleeding, heart issues, other invasive cancers within the last 3 years, untreated brain metastases, or those on certain drugs affecting liver enzymes are excluded.

Inclusion Criteria

You need to have certain levels of blood cells and chemicals in your blood for this study.

The effects of cediranib and olaparib on the developing human fetus are unknown; adequate contraception is required

You have been diagnosed with certain types of cancer that has spread or cannot be removed with surgery.

Exclusion Criteria

Any condition that, in the opinion of the treating investigator would interfere with evaluation of the investigational product or interpretation of subject safety or study results

You are using natural herbal products, alternative medications, or folk remedies.

You have had a significant amount of coughing up blood or bleeding in the past month.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cediranib maleate orally once daily and olaparib twice daily, with cycles repeating every 28 days (35 days for cycle 1) in the absence of disease progression or unacceptable toxicity

Up to 43 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cediranib Maleate
• Olaparib

Trial Overview The study tests a combination of two drugs: Cediranib Maleate and Olaparib in patients with various advanced solid tumors. The goal is to see if these drugs can stop tumor growth by inhibiting specific enzymes needed for cell proliferation and cutting off oxygen supply to the tumor cells.

How Is the Trial Designed?

Group I: Treatment (cediranib maleate, olaparib) Experimental Treatment 5 Interventions

Patients receive cediranib maleate PO QD on day 1. Patients undergoing FMISO scan also receive olaparib PO BID beginning the day after the second FMISO scan and the rest of the patients receive olaparib PO BID beginning day 4 of cycle 1. Cycles repeat every 28 days (35 days for cycle 1) in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

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

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 (Lynparza) is approved for treating adult patients with high-risk early breast cancer that has a germline BRCA mutation, following chemotherapy treatment.

This approval highlights Olaparib's role as an adjuvant therapy, which means it is used after initial treatments to help prevent cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjuvant Treatment for High-Risk Early Breast Cancer. Aschenbrenner, DS.[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 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. 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 ...

2. 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 ...

3. 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 ...

4. clinicaltrial.be clinicaltrial.be/en/details/10978?per_page=100&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Testing the Combination of Cediranib and Olaparib in Comp... ARM II (CEDIRANIB MALEATE AND OLAPARIB): Patients receive cediranib maleate orally (PO) once daily (QD) and olaparib PO twice daily (BID). Cycles repeat every ...

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

Cediranib and Olaparib Combination Compared ... - PubMed Median PFS was 3.4, 5.2, and 4 months with SOC, cediranib/olaparib, and cediranib, respectively, with a median follow-up duration of 42.2 months ...

6. dana-farber.org dana-farber.org/clinical-trials/18-714

"A Phase 2 Study of Cediranib in Combination with ... This phase II trial studies cediranib maleate in combination with olaparib in treating patients with solid tumors that have spread to other parts of the ...