ACP-196 for Glioblastoma

Not currently recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Acerta Pharma BV

Must be taking: Anticonvulsants

Must not be taking: Strong CYP3A4 inhibitors

Disqualifiers: Significant cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 3

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, ACP-196, as a potential treatment for recurrent glioblastoma, an aggressive brain cancer. Participants have already tried other treatments. The trial divides participants into two groups: one takes ACP-196 twice daily, and the other takes it once daily. Eligible individuals must show recurrent glioblastoma through an MRI scan. Those with three or more previous treatments for glioblastoma or certain other health issues may not qualify. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires that you be on a stable dose of any necessary medication, like anticonvulsants, for at least 3 weeks before starting the study drug. It doesn't specify stopping other medications, but you should discuss your current medications with the study team.

Is there any evidence suggesting that ACP-196 is likely to be safe for humans?

Research has shown that ACP-196, also known as acalabrutinib, has undergone safety testing in various situations. No new safety issues have emerged with this treatment. In studies, about 6% of patients discontinued use due to side effects. The most common reasons for stopping included infections like pneumonia and low platelet levels, which are cells that help blood clot. Overall, evidence suggests that acalabrutinib is generally well-tolerated. Prospective trial participants should know that this treatment has been tested and is manageable for most people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for glioblastoma?

ACP-196 is unique because it targets glioblastoma in a way that differs from standard treatments like surgery, radiation, and chemotherapy. Most treatments for glioblastoma focus on destroying tumor cells through mechanical removal or by using toxic agents to kill them. However, ACP-196, also known as acalabrutinib, is an oral medication that works by inhibiting Bruton's tyrosine kinase (BTK), an enzyme involved in the growth and survival of cancer cells. Researchers are excited about this approach because it offers a more targeted mechanism, potentially leading to better outcomes with fewer side effects. The study explores two dosing regimens: a 200 mg dose taken twice daily and a 400 mg dose taken once daily, providing flexibility in administration that might improve patient adherence and effectiveness.

What evidence suggests that ACP-196 might be an effective treatment for glioblastoma?

Research has shown that ACP-196, also known as acalabrutinib, may help treat recurrent glioblastoma multiforme, a type of brain cancer. Studies have found that acalabrutinib can significantly reduce the ability of glioblastoma cells to grow and spread, potentially slowing the cancer's progression. In animal studies, those treated with acalabrutinib lived longer than those who did not receive the treatment. These findings suggest that acalabrutinib could be a useful option for managing this aggressive cancer. Participants in this trial will receive ACP-196 in one of two dosing regimens: 200 mg administered orally twice per day or 400 mg administered orally once per day. ^{1 2 4 6 7}

Who Is on the Research Team?

Acerta Clinical Trials

Principal Investigator

1-888-292-9613; [e-mail]

Are You a Good Fit for This Trial?

This trial is for adults over 18 with recurrent Glioblastoma Multiforme (GBM) who've had prior therapy including temozolomide. Participants should have a life expectancy of at least 12 weeks, an ECOG status ≤2, and stable brain disease as seen on MRI. They must not have had more than two systemic therapies for GBM or certain other cancers within the last two years.

Inclusion Criteria

My steroid dose has been stable or decreasing for at least 5 days before my baseline MRI.

I can take care of myself but might not be able to do heavy physical work.

I have finished all my previous cancer treatments before starting ACP-196.

Exclusion Criteria

I have been treated with Avastin before.

I need treatment with a strong medication that affects liver enzymes.

Breastfeeding or pregnant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ACP-196 either 200 mg BID or 400 mg QD for recurrent GBM

8 weeks

Visits on Cycle 3 Day 1, Cycle 4 Day 1, and every 8 weeks thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ACP-196

Trial Overview The study tests ACP-196's effectiveness in treating GBM that has come back after treatment. It's open-label, meaning everyone knows they're getting ACP-196, and it involves multiple centers to gather diverse data.

How Is the Trial Designed?

Group I: Cohort 2 Experimental Treatment 1 Intervention

ACP-196 400mg administered orally (PO) once per day (QD).

Group II: Cohort 1 Experimental Treatment 1 Intervention

ACP-196 200 mg administered orally (PO) twice per day (BID)

Who Is Running the Clinical Trial?

Acerta Pharma BV

Lead Sponsor

Trials

46

Recruited

5,900+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02586857

A Phase 1b/2, Multicenter, Open-label Study of ACP-196 in ... A Phase 1b/2, multicenter, open-label study was designed to evaluate the efficacy and safety of acalabrutinib in subjects with recurrent glioblastoma ...

2. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/57/NCT02586857/Prot_003.pdf

Product: ACP-196 (Acalabrutinib) Protocol: ACE-ST-209 This Phase 1b/2, multicenter, open-label study is designed to evaluate the efficacy and safety of acalabrutinib in subjects with recurrent GBM who have ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8464793/

Combined Treatment with Acalabrutinib and Rapamycin ... Phenotypically, our results indicate that treatment with acalabrutinib markedly diminishes the sphere-formation and colony-formation abilities of GBM cells.

4. ucla.clinicaltrials.researcherprofiles.org ucla.clinicaltrials.researcherprofiles.org/trial/NCT02586857

ACP-196 in Subjects With Recurrent Glioblastoma Multiforme ... A Phase 1b/2, multicenter, open-label study was designed to evaluate the efficacy and safety of acalabrutinib in subjects with recurrent glioblastoma ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4784459/

Acalabrutinib (ACP-196): a selective second-generation ... Most interestingly, acalabrutinib treatment increased survival significantly over mice receiving vehicle (median 81 vs 59 days, P = 0.02). The ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0006497119848425

Pooled Analysis of Safety Data from Clinical Trials ... AEs led to treatment discontinuation in 37 (6.1%) pts. AEs leading to discontinuation in ≥2 pts included pneumonia (0.5%), thrombocytopenia (0.5 ...

7. hematologyadvisor.com hematologyadvisor.com/news/chronic-leukemia-cll-safety-profile-acalabrutinib-superior-chemoimmunotherapy/

Safety Profile of Acalabrutinib Superior to ... Outcomes comprised all-cause death, atrial fibrillation, hypertension, ventricular arrhythmias, acute heart failure, and bleeding. Acalabrutinib ...