Cediranib + Olaparib vs Bevacizumab for Recurrent Glioblastoma

Recruiting at 28 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

70 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Bevacizumab for recurrent glioblastoma?

Research shows that Bevacizumab, when used alone or with other drugs like irinotecan, can be effective for patients with recurrent glioblastoma, a type of brain cancer. It has been studied in several trials and shown to help manage symptoms and slow disease progression. ^{1 2 3 4 5}

Is the combination of Cediranib, Olaparib, and Bevacizumab safe for treating recurrent glioblastoma?

Bevacizumab has been shown to have manageable side effects, with severe treatment-related issues occurring in only a small number of patients. Cediranib has been studied in combination with other treatments for glioblastoma, but specific safety data for the combination of Cediranib, Olaparib, and Bevacizumab is not detailed in the available research. ^{3 6 7 8 9}

How is the drug combination of Cediranib, Olaparib, and Bevacizumab unique for treating recurrent glioblastoma?

This drug combination is unique because it combines Cediranib, which blocks blood vessel growth in tumors, with Olaparib, a drug that targets cancer cell repair mechanisms, and Bevacizumab, which also inhibits blood vessel growth. This multi-targeted approach aims to enhance treatment effectiveness by attacking the tumor from different angles. ^{9 10 11 12 13}

What is the purpose of this trial?

This trial compares two treatments for patients with glioblastoma that has returned. One treatment uses pills that block enzymes needed for tumor growth. The other treatment uses an IV drug that helps the immune system fight cancer and prevents tumors from growing. The goal is to see which treatment works better at stopping the cancer from progressing.

Research Team

Isabel Arrillaga-Romany

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Role of delayed salvage bevacizumab at symptomatic progression of chemorefractory glioblastoma. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Bevacizumab Alone and in Combination With Irinotecan in Recurrent Glioblastoma. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Phase 2 study of carboplatin, irinotecan, and bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Bevacizumab for the treatment of recurrent glioblastoma. [2023]

7. England 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. [2023]

8. England 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. [2020]

9. England pubmed.ncbi.nlm.nih.gov

What have we learned from trials on antiangiogenic agents in glioblastoma? [2014]

10. United States pubmed.ncbi.nlm.nih.gov

Multi-Center Randomized Phase II Study Comparing Cediranib plus Gefitinib with Cediranib plus Placebo in Subjects with Recurrent/Progressive Glioblastoma. [2021]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Cediranib, a pan-inhibitor of vascular endothelial growth factor receptors, inhibits proliferation and enhances therapeutic sensitivity in glioblastoma cells. [2021]

12. United States 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. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

Phase II study of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. [2022]