Adavosertib + Radiation + Temozolomide for Glioblastoma

No longer recruiting at 11 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must be taking: Corticosteroids

Must not be taking: EIAEDs, CYP3A4 inhibitors

Disqualifiers: Pregnancy, HIV, Uncontrolled illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and assess the side effects of combining adavosertib, radiation therapy, and temozolomide for treating glioblastoma, an aggressive brain cancer. Adavosertib is believed to block enzymes that aid tumor growth, while radiation uses X-rays to kill tumor cells, and temozolomide is a chemotherapy drug that inhibits their growth and spread. The study explores whether adding adavosertib to the standard treatment of radiation and temozolomide can improve outcomes for those with newly diagnosed or recurrent glioblastoma. Individuals diagnosed with glioblastoma, whether newly diagnosed or recurrent, may be suitable candidates for this trial. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants a chance to be among the first to receive this new therapy combination.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking enzyme-inducing anti-epileptic drugs at least 10 days before starting the study medication. You also cannot take certain drugs that affect the CYP3A4 enzyme or anti-coagulants other than low-molecular weight heparin. If you're on these medications, you may need to discuss alternatives with your doctor.

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

Research has shown that adavosertib, combined with radiation therapy and temozolomide, has been studied for safety. In one study, no drug-related side effects were reported, suggesting that adavosertib might be well-tolerated by patients. Another study found this combination generally safe for children with a different type of brain tumor, although it did not improve survival rates.

This trial is in an early stage, focusing primarily on determining the safest dose and understanding any side effects. As a result, detailed safety information may be limited. However, previous studies on adavosertib suggest some level of safety, especially when tested with other treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine adavosertib, temozolomide, and radiation in a novel way to tackle glioblastoma, a highly aggressive brain cancer. Unlike standard treatments that typically involve surgery, radiation, and temozolomide alone, this approach introduces adavosertib, a drug that targets cell division, potentially enhancing the treatment's effectiveness. This combination aims to disrupt cancer cell growth more effectively than current options, offering hope for better outcomes in a condition known for its resistance to treatment. By integrating these therapies, researchers are exploring whether this multi-pronged attack can improve survival rates and quality of life for patients.

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

This trial will compare two treatment approaches for glioblastoma. In one arm, participants will receive a combination of adavosertib, temozolomide, and radiation therapy. Research shows that this combination may improve treatment outcomes by slowing tumor growth and blocking key enzymes cancer cells need to multiply. Adavosertib specifically targets these enzymes to help prevent the cancer from spreading. In another arm, participants will receive adavosertib and temozolomide without radiation. Studies have found that using adavosertib with chemotherapy can lead to encouraging responses. Although these findings are still early, they suggest that these treatment combinations could yield better results than standard treatments alone. ^{1 4 5 6 7}

Who Is on the Research Team?

Eudocia Q Lee

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

This trial is for adults with new or recurrent glioblastoma who can provide tissue samples, have a decent performance status (able to care for themselves), normal organ and marrow function, no severe allergies to similar drugs, and not on certain medications. Women must test negative for pregnancy and agree to birth control.

Inclusion Criteria

Total bilirubin =< institutional upper limit of normal

AST/ALT =< 3 x institutional upper limit of normal

APTT/PTT =< 1.5 x institutional upper limit of normal

Exclusion Criteria

Patients receiving any other investigational agents are ineligible

Pregnant women are excluded from this study

I am not on any blood thinners except for low-molecular weight heparin.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initiation Cycle

Patients receive adavosertib and temozolomide with concurrent radiation therapy for 6 weeks

6 weeks

5 visits per week (in-person)

Maintenance Cycles

Patients receive temozolomide every 28 days for up to 6 cycles

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 2 months for 2 years, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Adavosertib
• Radiation Therapy
• Temozolomide

Trial Overview The trial tests the combination of adavosertib with radiation therapy and temozolomide chemotherapy in patients with glioblastoma. It aims to find the best dose of adavosertib that's effective when used alongside standard treatments without causing severe side effects.

How Is the Trial Designed?

Group I: Arm II (adavosertib, temozolomide) Experimental Treatment 2 Interventions

Patients receive adavosertib PO QD on days 1, 3, and 5 or 1-5 weekly, and temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (adavosertib, temozolomide, radiation) Experimental Treatment 3 Interventions

INITIATION CYCLE: Patients receive adavosertib PO on days 1, 3, and 5 or 1-5 weekly and temozolomide PO QD for 6 weeks. Patients also undergo concurrent radiation therapy 5 days per week for 6 weeks. MAINTENANCE CYCLES: Beginning in week 10, patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 6 cycles 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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11913579/

Phase I study of adavosertib with radiation therapy and ... INTRODUCTION. The prognosis for patients with glioblastoma (GBM) is poor with a median overall survival (OS) of 15–18 months despite maximal safe resection, ...

2. aacrjournals.org aacrjournals.org/clincancerres/article/31/6/983/753256/Phase-I-Study-of-Adavosertib-with-Radiotherapy-and

Phase I Study of Adavosertib with Radiotherapy and ... Introduction. The prognosis for patients with glioblastoma (GBM) is poor with a median overall survival of 15 to 18 months despite maximal safe resection, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01849146

Study Details | NCT01849146 | Adavosertib, Radiation ... Giving adavosertib, radiation therapy, and temozolomide may work better in treating patients with newly diagnosed or recurrent glioblastoma compared to ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39820282/

Phase I Study of Adavosertib with Radiotherapy and ... - PubMed A phase I study evaluating adavosertib in combination with radiation (RT) and temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GBM).

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.2568

Intratumoral drug distribution of adavosertib in patients with ... Methods: Twelve patients received five daily doses of adavosertib pre-operatively at either the maximum tolerated dose (MTD) for concurrent ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6865048/

Phase 0 Trial of AZD1775 in First-Recurrence Glioblastoma ... No drug-related adverse events were associated with this study. Conclusions: In contrast to recent preclinical data, our phase 0 study of AZD 1775 in recurrent ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9209747/

Wee1 kinase inhibitor adavosertib with radiation in newly ... Adavosertib in combination with CRT is well tolerated in children with newly diagnosed DIPG, however, compared to historical controls, did not improve OS.