Cediranib + Olaparib for Advanced Prostate Cancer

Not currently recruiting at 17 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: LHRH agonists

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Varies (up to 5 years)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of two drugs, olaparib and cediranib, in treating advanced prostate cancer that resists traditional hormone therapy and has metastasized. Olaparib (Lynparza) prevents cancer cells from repairing themselves, while cediranib (AZD2171) inhibits enzymes that promote cancer cell growth. The trial includes two groups: one receives both olaparib and cediranib, and the other receives only olaparib. Men with metastatic, hormone-resistant prostate cancer who have undergone at least one prior treatment may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) for specific drugs. If you are taking strong or moderate CYP3A inhibitors or inducers, you will need to stop them for a certain period before starting the trial. Additionally, natural herbal products must be stopped, but multivitamins and certain supplements are allowed.

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

Research has shown that combining the drugs cediranib and olaparib can benefit men with advanced prostate cancer that no longer responds to hormone therapy. However, this combination is more likely to cause side effects. Common side effects include nausea, anemia, loss of appetite, and fatigue.

Olaparib alone is usually well-tolerated and maintains a similar safety profile across different cancers. It can cause side effects like tiredness and nausea, but these are often manageable.

Considering these factors is important for those thinking about joining a trial with these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for advanced prostate cancer because they target the disease in novel ways. Cediranib is an oral medication that inhibits blood vessel growth in tumors, potentially starving the cancer. Olaparib, on the other hand, is a PARP inhibitor, which prevents cancer cells from repairing their DNA, leading to cell death. Unlike traditional hormone therapies or chemotherapy, this combination could offer a more targeted approach, possibly resulting in fewer side effects and improved outcomes for patients.

What evidence suggests that this trial's treatments could be effective for advanced prostate cancer?

This trial will compare the combination of cediranib and olaparib with olaparib alone for men with advanced prostate cancer that no longer responds to hormone therapy. Research has shown that combining cediranib and olaparib can lead to better outcomes, helping patients go longer without their cancer worsening compared to using olaparib alone. Olaparib, a PARP inhibitor, prevents cancer cells from repairing themselves and growing. Cediranib blocks certain enzymes that cancer cells need to grow. Together, these drugs appear more effective than olaparib alone in slowing cancer progression. ^{2 3 4 6 7}

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?

Men with advanced prostate cancer that has spread and is resistant to castration treatment. Participants must have had at least one prior therapy for metastatic castration-resistant prostate cancer (mCRPC), be able to swallow pills, and not have untreated brain metastases or a history of allergic reactions to similar drugs. They should also meet specific health criteria like controlled blood pressure, adequate organ function, and agree to use contraception.

Inclusion Criteria

Tumor lesion safely accessible for biopsy

Toxicities of prior therapy resolved to =< grade 1 as per NCI-CTCAE v5.0

Platelets >= 100,000/mcL

Exclusion Criteria

History of stroke or transient ischemic attack within 6 months of the randomization

You have experienced a blocked bowel within the month before starting the study.

You have taken any experimental drugs within the last 28 days before the start of the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive olaparib with or without cediranib in 28-day cycles until disease progression or unacceptable toxicity

Varies (up to 5 years)

Monthly visits for treatment cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 6 months

Biannual follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Cediranib
• Olaparib

Trial Overview The trial is testing if combining two oral medications, Cediranib and Olaparib, is more effective than using just Olaparib in men with advanced prostate cancer. The study will randomly assign participants into groups receiving either the combination or the single drug to compare their effects on tumor growth.

How Is the Trial Designed?

Group I: Arm A (olaparib, cediranib) Experimental Treatment 2 Interventions

Patients receive olaparib PO BID and cediranib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm B (olaparib) Active Control 1 Intervention

Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Olaparib is already approved in European Union, United States for the following indications:

Approved in European Union as Lynparza for:

• Breast cancer
• Ovarian cancer
• Fallopian tube cancer
• Peritoneal cancer
• Pancreatic cancer
• Prostate cancer
• Endometrial cancer

Approved in United States as Lynparza for:

• Ovarian, fallopian tube, and primary peritoneal cancer
• Breast cancer
• Prostate cancer
• Pancreatic cancer

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 2 trial involving 50 patients with metastatic, castration-resistant prostate cancer, treatment with the PARP inhibitor olaparib resulted in a 33% response rate, particularly among patients with DNA-repair gene defects, such as BRCA1/2 and ATM.

Among the 16 patients with identified DNA-repair defects, 88% responded to olaparib, highlighting the efficacy of this treatment in a specific subgroup of prostate cancer patients, while the most common side effects were anemia and fatigue, consistent with previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. Mateo, J., Carreira, S., Sandhu, S., et al.[2022]

Cediranib showed some anti-tumor activity in patients with metastatic castration-resistant prostate cancer (CRPC) who had previously undergone docetaxel treatment, with 43.9% of patients remaining progression-free at 6 months and a median progression-free survival of 3.7 months.

The treatment was generally well tolerated, with common side effects including hypertension and fatigue; however, adding prednisone helped reduce some of these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II clinical trial of cediranib in patients with metastatic castration-resistant prostate cancer. Dahut, WL., Madan, RA., Karakunnel, JJ., et al.[2023]

The combination of cediranib and olaparib did not show clinically meaningful activity in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who do not have a known BRCA mutation, as no objective responses were observed in the study of 19 patients.

Despite some patients experiencing stable disease for a median of 3.1 months, the overall survival was only 3.4 months, indicating limited efficacy of this treatment combination in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Activity and Safety of Cediranib and Olaparib Combination in Patients with Metastatic Pancreatic Ductal Adenocarcinoma without BRCA Mutation. Kim, JW., Cardin, DB., Vaishampayan, UN., et al.[2022]

In a phase 2 trial involving 142 patients with metastatic castration-resistant prostate cancer, the combination of olaparib and abiraterone significantly improved radiographic progression-free survival (rPFS) to a median of 13.8 months compared to 8.2 months with placebo and abiraterone, indicating enhanced efficacy of the treatment.

While the combination treatment showed clinical benefits, it also resulted in a higher incidence of serious adverse events, including a treatment-related death, suggesting that while effective, the combination may carry increased risks that need to be managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial. Clarke, N., Wiechno, P., Alekseev, B., et al.[2019]

The combination of niraparib, a PARP inhibitor, with Radium-223 was found to be safe for treating metastatic castrate-resistant prostate cancer (mCRPC) in men without known BRCA mutations, with manageable dose-limiting toxicities (DLTs) primarily related to blood cell counts.

In a study of 30 patients, the maximum tolerated dose (MTD) varied based on prior chemotherapy exposure, indicating that personalized dosing may be necessary; further research is needed to explore biomarkers that could predict treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Niraparib in Combination with Radium-223 for the Treatment of Metastatic Castrate-Resistant Prostate Cancer. Quinn, Z., Leiby, B., Sonpavde, G., et al.[2023]

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/36256912/

The Results From National Cancer Institute 9984 - PubMed Cediranib combined with olaparib improved rPFS compared with olaparib alone in men with mCRPC. This combination was associated with an increased incidence of ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.02947

Randomized Trial of Olaparib With or Without Cediranib for ... Cediranib combined with olaparib improved rPFS compared with olaparib alone in men with mCRPC. This combination was associated with an increased incidence of ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02893917

Study Details | NCT02893917 | Testing Two Oral Drugs ... This randomized phase II trial studies how well olaparib with or without cediranib works in treating patients with castration-resistant prostate cancer that ...

4. lynparza.com lynparza.com/prostate-cancer/results.html

Metastatic Prostate Cancer Treatment Results The median time of survival after the start of LYNPARZA was 19.1 months vs 14.7 months on enzalutamide or abiraterone. FOR ADULTS WITH BRCA1, BRCA2, OR ATM ...

5. onclive.com onclive.com/view/cediranib-plus-olaparib-elicits-rpfs-benefit-in-metastatic-castration-resistant-prostate-cancer

Cediranib Plus Olaparib Elicits rPFS Benefit in Metastatic ... The combination of cediranib and olaparib significantly improved radiographic progression-free survival compared with olaparib monotherapy ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8265343/

Clinical Activity and Safety of Cediranib and Olaparib ... Cediranib and olaparib combination did not result in clinically meaningful activity in patients with mPDAC without gBRCAmt.

7. ejcancer.com ejcancer.com/article/S0959-8049(22)00217-9/fulltext

Olaparib tolerability and common adverse-event ... The safety profile of olaparib in men with mCRPC was similar to other solid tumours. Events of anaemia, nausea, decreased appetite and fatigue occurred most ...