What is the mechanism of action of this treatment?

Common treatments for Glioblastoma, such as Cediranib Maleate and Olaparib, work by inhibiting critical enzymes that support tumor growth and survival. Cediranib Maleate blocks VEGF receptors, reducing angiogenesis and thus starving the tumor of necessary blood supply. Olaparib inhibits PARP enzymes, preventing cancer cells from repairing DNA damage, leading to cell death. These mechanisms are significant for Glioblastoma patients as they directly target the tumor's growth and repair pathways, potentially slowing disease progression and improving survival rates.

What side effects are associated with this type of intervention?

Common treatments for glioblastoma, such as enzyme inhibitors like Cediranib Maleate and Olaparib, and immunotherapy with monoclonal antibodies like Bevacizumab, have several known side effects. These can include headache, fatigue, nausea, hypertension, and diarrhea. Additionally, Bevacizumab may cause more specific issues such as epistaxis (nosebleeds), dry eye, and conjunctivitis. Severe side effects, though less common, can include neutropenia, ulcerative keratitis, and peripheral neuropathies.

What prior FDA approvals exist?

FDA-approved treatments for glioblastoma that involve enzyme inhibition include Bevacizumab, a monoclonal antibody that inhibits vascular endothelial growth factor (VEGF) to prevent tumor growth. Other treatments like Temozolomide, an alkylating agent, are also used but do not specifically target enzymes in the same way as Cediranib Maleate and Olaparib. These drugs aim to block the enzymes needed for cell growth, similar to the mechanism being studied in the trial involving Cediranib Maleate and Olaparib.

What other types of research exist?

Promising novel alternatives for glioblastoma treatment in 2024 include Bevacizumab, which is an immunotherapy with monoclonal antibodies. Additionally, other agents under investigation include Pembrolizumab and Atezolizumab, which are being evaluated in clinical trials for their efficacy in treating glioblastoma.

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Monoclonal Antibodies

Cediranib + Olaparib vs Bevacizumab for Recurrent Glioblastoma

Phase 2

Waitlist Available

Led By Isabel Arrillaga-Romany

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Only first and second recurrences of GBM are eligible

Creatinine should not exceed the institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2

Must not have

Patients with myelodysplastic syndrome/acute myeloid leukemia

Participants may not have had any prior history of hypertensive crisis or hypertensive encephalopathy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years

Awards & highlights

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include high blood pressure, fatigue, risk of bleeding or clotting issues due to blood vessel effects from cediranib/bevacizumab; nausea; diarrhea; low blood counts leading to infection risk; allergic reactions; possible harm to unborn babies.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My GBM has recurred no more than twice.

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My kidney function tests are within normal range.

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My corticosteroid dose has been stable or decreasing for the last 5 days.

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My brain scans show my tumor is growing, or I have a confirmed recurrent glioblastoma.

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I can care for myself but may need occasional help.

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My hemoglobin is at least 10.0 g/dL and I haven't had a blood transfusion in the last 28 days.

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All my side effects from previous treatments are gone, except maybe for hair loss.

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I have been treated with radiotherapy and temozolomide before.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been diagnosed with myelodysplastic syndrome or acute myeloid leukemia.

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I have never had a hypertensive crisis or brain issues due to high blood pressure.

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I have early-stage breast or cervical cancer.

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I have unstable chest pain.

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I have not had any abdominal openings or gut tears in the last 6 months.

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I have moderate to severe heart failure.

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I have a serious blood vessel condition like an aortic aneurysm.

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My heart's pumping ability is normal or above 55%.

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I am not pregnant or breastfeeding.

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I do not have any serious illnesses that are not under control.

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I have not used PARP inhibitors or drugs affecting the VEGF pathway.

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I have serious blood vessel problems in my arms or legs.

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I had a heart attack in the last six months.

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I have been treated for early-stage skin cancer.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of Participants With Progression-Free Survival at 6 Months

Secondary study objectives

Imaging Correlates (Vascular Permeability, Tumor Perfusion and Oxygenation, Brain Tumor Cellularity)

Incidence of Adverse Events (AE)

Levels of Circulating Cytokines Involved With Angiogenesis

+4 more

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm B (bevacizumab)Experimental Treatment1 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 Treatment3 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Bevacizumab

2013

Completed Phase 4

~5540

Cediranib

2016

Completed Phase 3

~4030

Cediranib Maleate

2010

Completed Phase 2

~660

Olaparib

2007

Completed Phase 4

~2190

0 / 22Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Glioblastoma, such as Cediranib Maleate and Olaparib, work by inhibiting critical enzymes that support tumor growth and survival. Cediranib Maleate blocks VEGF receptors, reducing angiogenesis and thus starving the tumor of necessary blood supply. Olaparib inhibits PARP enzymes, preventing cancer cells from repairing DNA damage, leading to cell death. These mechanisms are significant for Glioblastoma patients as they directly target the tumor's growth and repair pathways, potentially slowing disease progression and improving survival rates.