Pembrolizumab for Pediatric Brain Cancer

Not currently recruiting at 13 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Systemic steroids, Immunosuppressive agents

Disqualifiers: Autoimmune disease, Pneumonitis, Other malignancies, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 38

Duration: 25.5 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the safety and optimal dosage of pembrolizumab, a type of immunotherapy, for treating children and young adults with aggressive or recurring brain tumors such as high-grade gliomas, ependymoma, and medulloblastoma. Researchers hope pembrolizumab will enhance the immune system's ability to fight these tumors. This trial may suit young patients whose brain tumors have not responded to previous treatments like radiation or chemotherapy. As a Phase 1 trial, the research focuses on understanding how pembrolizumab works in people, offering participants the opportunity to be among the first to receive this treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must have recovered from any recent treatments and meet certain time requirements since your last dose of specific therapies before enrolling.

Is there any evidence suggesting that pembrolizumab is likely to be safe for humans?

Research has shown that pembrolizumab, a type of immunotherapy, has been tested for safety in young patients with brain tumors. One study found it mostly safe, with only one child experiencing a severe headache as a side effect. This indicates that pembrolizumab is generally well-tolerated in children. The FDA has approved pembrolizumab for treating certain conditions in both adults and children, but its safety for brain cancers in children remains unconfirmed. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pembrolizumab is unique because it targets the PD-1 pathway, which is a novel approach compared to traditional treatments for pediatric brain cancer. Most current treatments involve chemotherapy and radiation, which can have significant side effects and long-term impacts. Pembrolizumab, on the other hand, is an immunotherapy that works by boosting the body’s own immune system to recognize and fight cancer cells more effectively. Researchers are excited about its potential to offer a more targeted treatment with possibly fewer side effects, providing a new hope for young patients battling this challenging disease.

What evidence suggests that pembrolizumab might be an effective treatment for pediatric brain cancer?

Research has shown that pembrolizumab, a type of immunotherapy, can help the body's immune system fight cancer. This medicine targets and disrupts tumor growth. Studies on similar conditions have found that pembrolizumab may slow the growth of aggressive brain tumors. Specifically, early results in children with difficult-to-treat brain tumors suggest that pembrolizumab might help control or reduce these tumors. Although more research is needed, these early findings offer hope for improving outcomes in children with challenging brain cancers. Participants in this trial will receive pembrolizumab as the investigational treatment. ^{1 2 3 6 7}

Who Is on the Research Team?

Eugene I Hwang

Principal Investigator

Pediatric Brain Tumor Consortium

Are You a Good Fit for This Trial?

This trial is for young patients under 22 with specific brain tumors (high-grade gliomas, diffuse intrinsic pontine gliomas, hypermutated brain tumors, ependymoma or medulloblastoma) that are recurrent, progressive or refractory. They must have finished previous treatments and recovered from their effects. Participants need a performance score of >=70 and meet various health criteria including stable neurological deficits and adequate blood counts.

Inclusion Criteria

I am willing to take steroids for short periods if needed for side effects.

I agree to use two forms of birth control or abstain from sex for 4 months after the last dose.

My DIPG has not improved or has worsened after radiation therapy.

Exclusion Criteria

I don't have an active autoimmune disease needing ongoing steroids or immunosuppressants.

I am not currently on any cancer treatment or experimental drugs.

I have or had lung inflammation or significant lung disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive pembrolizumab intravenously every 21 days for up to 34 cycles

25.5 months

34 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Every 3 months for 1 year, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The trial tests the safety and effectiveness of pembrolizumab in treating aggressive pediatric brain tumors. It's a phase I study to determine the best dose while observing how well it works against these cancers by potentially altering the immune system to hinder tumor growth.

How Is the Trial Designed?

Group I: Treatment (pembrolizumab) Experimental Treatment 8 Interventions

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for 34 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo standard MRI, DCE permeability MRI, DTI, DSC perfusion MRI, MR diffusion imaging and may undergo MR spectroscopy as well as CSF and blood sample collection during screening and on study.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab, a PD-1 inhibitor, has received accelerated FDA approval for treating both adult and pediatric patients with solid tumors that are mismatch repair-deficient or microsatellite instability-high.

This approval marks a significant milestone as it is the first instance where the FDA has approved a cancer treatment based on a common biomarker rather than the specific type of tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First Tissue-Agnostic Drug Approval Issued. [2021]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

In a study involving 154 pediatric patients with advanced cancer, pembrolizumab was found to be well tolerated, with no dose-limiting toxicities reported, establishing a recommended phase 2 dose of 2 mg/kg every 3 weeks.

While pembrolizumab showed promising antitumor activity in patients with relapsed or refractory Hodgkin lymphoma (60% objective response rate), it demonstrated low efficacy in most other pediatric tumor types, indicating that PD-L1 expression alone may not be a reliable biomarker for predicting treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in paediatric patients with advanced melanoma or a PD-L1-positive, advanced, relapsed, or refractory solid tumour or lymphoma (KEYNOTE-051): interim analysis of an open-label, single-arm, phase 1-2 trial. Geoerger, B., Kang, HJ., Yalon-Oren, M., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02359565

Study Details | NCT02359565 | Pembrolizumab in Treating ... This phase I trial studies the side effects and best dose of pembrolizumab and to see how well it works in treating younger patients with high-grade gliomas ...

2. pbtc.org pbtc.org/public/Summaries/PBTC-045/045%20Abstract%20and%20Schema%20for%20Professionals.pdf

PBTC-045: A Safety and Preliminary Efficacy trial of MK- ... Abstract and Schema. This is a two phase safety and preliminary efficacy study. The first phase is a safety study to assess the dose limiting toxicities and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9834947/

Immunotherapy for the treatment of pediatric brain tumors Long term overall survival rates for pediatric CNS tumors approach 70%. However, there remains a portion of tumor types in which survival outcomes remain dismal ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6784275/

Immunotherapy for pediatric brain tumors: past and present This work reviews the history and advances in active immunotherapy, checkpoint blockade, and adoptive T-cell therapy for pediatric brain tumors.

5. withpower.com withpower.com/trial/phase-1-medulloblastoma-4-2015-774bd

Pembrolizumab for Pediatric Brain Cancer This trial studies the safety and effectiveness of pembrolizumab in younger patients with aggressive or treatment-resistant brain tumors.

6. stjude.org stjude.org/care-treatment/clinical-trials/pbtc45-pediatric-brain-tumor.html

PBTC45: MK-3475 in Treating Children with Recurrent ... This clinical trial studies the side effects and best dose of MK-3475 (pembrolizumab) and to see how well it works in treating younger patients with high-grade ...

7. merck.com merck.com/news/fda-approves-mercks-keytruda-pembrolizumab-for-adult-and-pediatric-patients-with-unresectable-or-metastatic-microsatellite-instability-high-msi-h-or-mismatch-repair-deficient-dmmr/

FDA Approves Merck's KEYTRUDA® (pembrolizumab) for ... The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.