Cediranib + Olaparib vs Bevacizumab for Recurrent Glioblastoma

Not currently recruiting at 32 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: PARP inhibitors, VEGF pathway

Disqualifiers: Hypertension, Myocardial infarction, HIV, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two treatments for recurrent glioblastoma, a type of brain cancer that returns after initial treatment. One group receives a combination of cediranib maleate and olaparib, which block certain enzymes to stop tumor growth. The other group receives bevacizumab (also known as Avastin), an immunotherapy that aids the immune system in attacking the cancer. Suitable candidates for this trial have experienced glioblastoma recurrence after radiation and temozolomide treatment and show evidence of the disease on a CT or MRI scan. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does mention that you cannot use certain medications that strongly interact with the trial drugs. You should 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?

Previous studies have tested the combination of cediranib maleate and olaparib for safety in cancer treatment. Research shows that this combination is generally well-tolerated, though some patients have experienced side effects such as tiredness and high blood pressure, which are common with this type of treatment.

Bevacizumab, already approved for other conditions, has extensive safety information available. It is generally considered safe but can cause side effects like high blood pressure and headaches.

Both treatments have been studied in clinical settings, and while side effects can occur, they are often manageable. Consider this information and discuss it with healthcare providers when thinking about joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because Cediranib and Olaparib offer a fresh approach to tackling recurrent glioblastoma, a tough brain cancer. Unlike the standard treatment Bevacizumab, which mainly focuses on cutting off the tumor's blood supply, Cediranib is a VEGFR inhibitor that also targets blood vessel growth, but with a different mechanism, potentially enhancing its effectiveness. Olaparib, on the other hand, is a PARP inhibitor that interferes with the cancer cells' ability to repair their DNA, possibly making them more vulnerable to treatment. Together, Cediranib and Olaparib provide a dual-action strategy that could offer new hope for patients with this challenging condition.

What evidence suggests that this trial's treatments could be effective for recurrent glioblastoma?

In this trial, participants will receive either a combination of cediranib maleate and olaparib or bevacizumab to treat recurrent glioblastoma, a type of brain cancer. Studies have tested the combination of cediranib maleate and olaparib, which is believed to block enzymes that aid cancer cell growth. However, research showed that this combination did not significantly improve the time patients lived without disease progression or their overall survival. In contrast, bevacizumab, another treatment option in this trial, uses antibodies to help the immune system fight cancer and has been known to slow tumor growth and spread in some patients. These findings suggest that while bevacizumab has shown some effectiveness, the combination of cediranib and olaparib has not provided significant benefits for this condition. ^{2 4 5 6 7}

Who Is on the Research Team?

Isabel Arrillaga-Romany

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with recurrent glioblastoma who've had prior radiotherapy and temozolomide treatment. Eligible participants must have stable or decreasing corticosteroid doses, adequate organ function, no severe allergies to the drugs being tested, and not be pregnant or breastfeeding. They should agree to use contraception and have a life expectancy of at least 3 months.

Inclusion Criteria

Leukocytes >= 3,000/mcL

My GBM has recurred no more than twice.

It's been over 12 weeks since my last radiotherapy, or my cancer has grown outside the treated area if it's been less.

Exclusion Criteria

I have not had an abdominal abscess in the last 6 months.

I have never had pneumonitis.

Participants may not have a dependency on IV hydration or total parenteral nutrition (TPN)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either olaparib and cediranib maleate or bevacizumab. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

6 months

Bi-weekly visits for Arm B, monthly visits for Arm A

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and then periodically for 3 years.

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Cediranib Maleate
• Olaparib

Trial Overview The study compares cediranib maleate plus olaparib against bevacizumab in treating recurrent glioblastoma. Cediranib maleate and olaparib are thought to block enzymes needed for tumor growth, while bevacizumab is an immunotherapy that may inhibit cancer spread.

How Is the Trial Designed?

Group I: Arm B (bevacizumab) Experimental Treatment 1 Intervention

Patients receive bevacizumab IV over 30-90 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm A (olaparib, cediranib maleate) Experimental Treatment 3 Interventions

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

Bevacizumab is already approved in European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian 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 a phase III clinical trial involving 325 patients with recurrent glioblastoma, cediranib did not significantly improve progression-free survival compared to lomustine alone, whether used as a monotherapy or in combination.

Despite not meeting the primary endpoint, cediranib demonstrated some clinical benefits in secondary outcomes, such as delaying neurological deterioration and reducing the need for corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. Batchelor, TT., Mulholland, P., Neyns, B., et al.[2022]

Bevacizumab, a monoclonal antibody targeting VEGF, has shown improved patient outcomes in recurrent glioblastoma (GBM) when used in combination with chemotherapy, leading to its accelerated approval by the FDA based on positive results from phase 2 studies.

The treatment is associated with manageable toxicity, as severe adverse events occur in only a small percentage of patients, making it a safer option for those with recurrent GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab for the treatment of recurrent glioblastoma. Chamberlain, MC.[2023]

In a study of 48 patients with recurrent glioblastoma, single-agent bevacizumab demonstrated significant biological activity, with 71% of patients achieving a radiographic response and a median progression-free survival of 16 weeks.

However, the combination of bevacizumab with irinotecan showed no objective responses, highlighting that while bevacizumab is effective as a standalone treatment, its efficacy may not extend when combined with certain other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. Kreisl, TN., Kim, L., Moore, K., et al.[2022]

In a phase II trial involving 296 patients with recurrent glioblastoma, continuing treatment with bevacizumab (BEV) after first-line therapy did not show a survival benefit compared to placebo, with median survival times of 6.4 months for BEV and 5.5 months for placebo.

The study found no new safety concerns with BEV treatment, as the incidence of severe treatment-related adverse events was similar between the BEV and placebo groups (19% vs. 15%), indicating that BEV can be safely administered through multiple lines of therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Phase II Trial (TAMIGA) Evaluating the Efficacy and Safety of Continuous Bevacizumab Through Multiple Lines of Treatment for Recurrent Glioblastoma. Brandes, AA., Gil-Gil, M., Saran, F., et al.[2020]

In a phase II clinical trial involving 158 patients with newly diagnosed glioblastoma, cediranib combined with radiation and temozolomide significantly improved 6-month progression-free survival (PFS) to 46.6% compared to 24.5% for the placebo group (P = 0.005).

Although cediranib showed efficacy in prolonging PFS, it was associated with a higher incidence of grade ≥3 adverse events compared to placebo (P = 0.02), and there was no significant difference in overall survival between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NRG/RTOG 0837: Randomized, phase II, double-blind, placebo-controlled trial of chemoradiation with or without cediranib in newly diagnosed glioblastoma. Batchelor, TT., Won, M., Chakravarti, A., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02974621

Study Details | NCT02974621 | Cediranib Maleate and ... This randomized phase II trial studies how well cediranib maleate and olaparib work compared to bevacizumab in treating patients with glioblastoma that has ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6847111/

ACTR-61. A RANDOMIZED PHASE 2 TRIAL OF ... Treatment with cediranib/olaparib failed to increase PFS and OS in patients with recurrent GBM. Blood, tissue and imaging correlates will be presented.

3. withpower.com withpower.com/trial/phase-3-glioblastoma-8-2017-aa0af

Cediranib + Olaparib vs Bevacizumab for Recurrent ... This trial compares two treatments for patients with glioblastoma that has returned. One treatment uses pills that block enzymes needed for tumor growth.

4. dana-farber.org dana-farber.org/clinical-trials/17-735

A randomized phase 2 trial of cediranib and olaparib ... This randomized phase II trial studies how well cediranib maleate and olaparib work compared to bevacizumab in treating patients with glioblastoma that has ...

5. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT02974621

Cediranib Maleate and Olaparib Compared to ... This randomized phase II trial studies how well cediranib maleate and olaparib work compared to bevacizumab in treating patients with glioblastoma that has ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02974621

Study Details | NCT02974621 | Cediranib Maleate and ... This randomized phase II trial studies how well cediranib maleate and olaparib work compared to bevacizumab in treating patients with glioblastoma that has ...

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2016-01769

Cediranib Maleate and Olaparib Compared to ... This randomized phase II trial studies how well cediranib maleate and olaparib work compared to bevacizumab in treating patients with glioblastoma that has ...