Personalized Treatment for Recurrent Glioblastoma

Recruiting at 1 trial location

Overseen By Michelle Kan

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: AHS Cancer Control Alberta

Must not be taking: Strong CYP3A/p-gp inducers

Disqualifiers: Abnormal LVEF, Severe hepatic impairment, Active hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new personalized treatment approach for recurrent glioblastoma, a type of brain cancer. The goal is to evaluate how well different drugs, such as Afatinib and Dasatinib, work when selected based on the specific genetic makeup of each patient's tumor. Participants will receive one of five study drugs tailored to their tumor's genetic profile. The trial seeks adults whose glioblastoma has returned after initial treatments and who can undergo surgery again. The researchers aim to determine if a larger study could be successful in the future. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude patients on strong CYP3A/p-gp inducers like carbamazepine and phenytoin. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

Research shows that the treatments tested in this study have undergone safety checks in earlier studies.

For **Afatinib**, research indicates it is generally safe for brain cancer patients. Taken orally, it was safe up to a dose of 280 mg once a week.

**Dasatinib** has been tested in patients with glioblastoma. The most common side effects were diarrhea and tiredness, mostly mild.

**Everolimus** is already approved for other types of cancer and has been used safely. Common side effects include mouth sores, infections, and skin rash.

**Olaparib** has been tested with glioblastoma patients and was safe with some mild side effects when used with other treatments.

For **Palbociclib**, safety data shows it was well-tolerated when combined with other therapies, with mostly mild side effects.

This trial is in its early phase, so researchers are closely monitoring these drugs for safety in this specific setting. However, earlier studies suggest they are generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for recurrent glioblastoma because they offer a personalized approach, unlike the standard chemotherapy and radiation options. Each drug in the trial—Afatinib, Dasatinib, Everolimus, Olaparib, and Palbociclib—targets specific mutations in the tumor, offering a tailored treatment strategy based on the genetic makeup of the cancer. This approach has the potential to be more effective because it directly addresses the unique characteristics of an individual's tumor rather than applying a one-size-fits-all treatment. By focusing on the tumor's specific mutation profile, these drugs could lead to better outcomes and fewer side effects compared to current standard treatments.

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

Research has shown that the success of these treatments for recurrent glioblastoma varies. In this trial, participants will receive one of five study drugs based on their recurrent tumor mutation profile and organoid response to these drugs. Afatinib has had limited success on its own, with some patients experiencing partial improvements. Dasatinib showed promise in early lab studies, but results in people have been mixed, with some decrease in tumor growth. Everolimus has helped stabilize the disease in some patients by affecting certain cell pathways. Olaparib has effectively reached glioblastoma cells, and some patients have remained stable for several months. Palbociclib, however, has not been very effective for recurrent glioblastoma. Overall, these treatments have shown different results, and their effectiveness might depend on individual genetic differences. ^{1 4 6 7 8}

Who Is on the Research Team?

Paula de Robles, MD

Principal Investigator

Arthur J.E. Child Comprehensive Cancer Centre

Are You a Good Fit for This Trial?

Adults over 18 with recurrent glioblastoma, not breastfeeding or pregnant, and willing to use contraception. Participants must have a performance status allowing daily activity (ECOG ≤2), be able to undergo brain MRIs, and have tumors suitable for resection. Excluded are those with certain heart, liver, kidney issues; gastrointestinal disorders; active infections; recent investigational drug use; other cancer treatments; or known psychiatric/substance abuse issues.

Inclusion Criteria

I am an adult with a specific type of brain tumor that has come back after initial treatments.

I agree not to donate sperm for 6 months during the study.

I agree to use two effective birth control methods if I can have children.

Exclusion Criteria

I am unable to give consent by myself.

Hypersensitivity to any ingredients in the study drugs or their excipients.

Subject will not be available for protocol-required study visits or procedures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive personalized study treatment based on the genetic profile of their recurrent GBM tumor

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Afatinib
• Dasatinib
• Everolimus
• Olaparib
• Palbociclib

Trial Overview

The trial is testing a personalized treatment regimen based on the genetic profile of each patient's tumor using drugs like Everolimus, Olaparib, Dasatinib, Afatinib, Palbociclib. It's an early-stage study to see if it's feasible to conduct larger trials and gather initial data on these interventions in patients with recurrent glioblastoma.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 5 Interventions

Patients will receive one of the 5 study drugs based on their recurrent tumor mutation profile and their recurrent organoid response to these drugs: 1. Afatinib 2. Dasatinib 3. Palbociclib 4. Everolimus 5. Olaparib

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

Approved in United States as Gilotrif for:

• Non-small cell lung cancer

Approved in European Union as Giotrif for:

• Non-small cell lung cancer

Approved in Canada as Gilotrif for:

• Non-small cell lung cancer

Approved in Japan as Giotrif for:

• Non-small cell lung cancer

Who Is Running the Clinical Trial?

AHS Cancer Control Alberta

Lead Sponsor

Trials

188

Recruited

26,900+

Tom Baker Cancer Centre

Collaborator

Trials

30

Recruited

8,900+

Published Research Related to This Trial

In a study of 31 patients with recurrent glioblastoma treated with apatinib and temozolomide, the combination showed an objective response rate of 26.3% and a disease control rate of 84.2%, indicating it can be an effective treatment option.

The treatment resulted in a median progression-free survival of 4.9 months and overall survival of 8.2 months, with manageable side effects such as hypertension and decreased appetite, suggesting it is a viable salvage therapy for this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apatinib Plus Temozolomide: An Effective Salvage Treatment for Recurrent Glioblastoma. Ge, J., Li, C., Xue, F., et al.[2022]

In a phase I study involving patients with newly diagnosed glioblastoma, the maximum tolerated dose (MTD) of buparlisib when combined with temozolomide was determined to be 80 mg/day, but the MTD for the combination with both temozolomide and radiotherapy could not be established due to significant dose-limiting toxicities.

The study reported high rates of adverse events, particularly nausea and fatigue, leading to treatment discontinuations, which contributed to Novartis's decision to halt further development of buparlisib for this indication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I, open-label, multicentre study of buparlisib in combination with temozolomide or with concomitant radiation therapy and temozolomide in patients with newly diagnosed glioblastoma. Wen, PY., Rodon, JA., Mason, W., et al.[2021]

In a study involving 88 patients with recurrent glioblastoma, the combination of bevacizumab and the PI3K inhibitor BKM120 showed a median progression-free survival of 4.0 months, which is comparable to results seen with bevacizumab alone.

Despite the potential efficacy, the combination treatment was poorly tolerated, with 57% of patients experiencing serious treatment-related toxicities, leading to the conclusion that further development of this regimen is not recommended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II study of bevacizumab with BKM120, an oral PI3K inhibitor, in patients with refractory solid tumors (phase I) and relapsed/refractory glioblastoma (phase II). Hainsworth, JD., Becker, KP., Mekhail, T., et al.[2020]

In a study of 21 patients with recurrent glioblastoma, the combination of anlotinib and temozolomide resulted in a high objective response rate of 81% and a median progression-free survival of 7.3 months, indicating significant efficacy in managing this aggressive cancer.

The treatment was generally well-tolerated, with the most common side effects being leukocytopenia and thrombocytopenia, and no treatment-related deaths were reported, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Anlotinib Hydrochloride Plus Temozolomide in Patients with Recurrent Glioblastoma. Xu, Q., Huang, K., Meng, X., et al.[2023]

In a phase Ib/II study involving 35 patients with recurrent glioblastoma, the maximum tolerable dose (MTD) of the pan-PI3K inhibitor buparlisib was established at 100 mg per day when combined with carboplatin, showing a consistent safety profile without new safety concerns.

However, the combination of buparlisib with either carboplatin or lomustine did not demonstrate sufficient antitumor activity compared to historical data for these single-agent treatments, indicating limited efficacy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buparlisib plus carboplatin or lomustine in patients with recurrent glioblastoma: a phase Ib/II, open-label, multicentre, randomised study. Rosenthal, M., Clement, PM., Campone, M., et al.[2021]

In a phase II trial involving 49 patients with recurrent glioblastoma and EGFR amplification, dacomitinib showed limited efficacy, with a 6-month progression-free survival rate of only 10.6%.

The treatment was associated with significant adverse effects, as 40.8% of patients experienced grade 3-4 drug-related side effects, primarily diarrhea and rash, highlighting the need for careful patient selection based on molecular characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of dacomitinib, a pan-human EGFR tyrosine kinase inhibitor, in recurrent glioblastoma patients with EGFR amplification. Sepúlveda-Sánchez, JM., Vaz, MÁ., Balañá, C., et al.[2022]

Dasatinib, a multitargeted tyrosine kinase inhibitor, was evaluated in a phase II trial for adults with recurrent glioblastoma, but the study found it ineffective, with no radiographic responses and a median overall survival of only 7.9 months.

Although intrapatient dose escalation was feasible and tolerated by some participants, the clinical benefit was insufficient, leading to the trial's closure without proceeding to further stages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 trial of dasatinib in target-selected patients with recurrent glioblastoma (RTOG 0627). Lassman, AB., Pugh, SL., Gilbert, MR., et al.[2019]

In a phase II study involving 33 patients with recurrent glioblastoma, dovitinib did not show efficacy in prolonging progression-free survival (PFS) at 6 months, with only 12% in the anti-angiogenic naïve group achieving this compared to 0% in the pretreated group.

The study revealed significant toxicity, with 67% of patients experiencing grade 3 toxicities and 15% experiencing grade 4 toxicities, indicating that while dovitinib was not effective, it did pose safety concerns for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of Dovitinib in recurrent glioblastoma. Sharma, M., Schilero, C., Peereboom, DM., et al.[2020]

In a study of 24 patients with recurrent glioblastoma, those whose tumors expressed imatinib targets showed better responses to oral imatinib, with 12 patients achieving tumor stabilization for 2.6 to 13.4 months and 6 patients surviving over a year.

Imatinib was well tolerated among patients, and while the median progression-free survival was 3 months and overall survival was 6 months, the findings suggest that identifying patients with specific tumor characteristics may help select those who could benefit more from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response to imatinib as a function of target kinase expression in recurrent glioblastoma. Hassler, MR., Vedadinejad, M., Flechl, B., et al.[2022]

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