Pembrolizumab + Spine Radiosurgery for Spinal Tumors

Overseen By Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Wake Forest University Health Sciences

Must be taking: Pembrolizumab

Must not be taking: Investigational agents

Disqualifiers: Lymphoma, Brain metastases, Pregnancy, 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

Compensation: Varies

Number of Visits: 3

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates the effects of combining pembrolizumab (a type of immunotherapy) with stereotactic body radiation therapy (a precise form of radiation) on spinal tumors. The research targets participants with high-grade epidural disease in the spine, a severe condition where cancer spreads to the space surrounding the spinal cord. The goal is to assess how these treatments work together regarding benefits and side effects. Eligible participants have been diagnosed with cancer affecting the spine and have not received previous radiation or surgery on the affected area. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative combination therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, you cannot be on any other investigational drugs while participating in this study.

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

Research has shown that pembrolizumab, combined with stereotactic body radiation therapy (SBRT), is generally safe and well-tolerated. Studies have found that this combination can be administered safely by precisely targeting the radiation to protect healthy tissues.

Pembrolizumab, a treatment that helps the immune system fight cancer, is already used for other cancer types. However, its use with SBRT remains under investigation. So far, patients receiving both treatments have not encountered any unexpected safety issues.

Overall, evidence suggests that these treatments together do not cause severe side effects for most patients. However, as this is an early trial, more information is needed to fully understand all possible risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about combining Pembrolizumab with stereotactic body radiation therapy (SBRT) for spinal tumors because it offers a novel approach to treatment. Pembrolizumab is an immunotherapy drug that works by unleashing the body's immune system to attack cancer cells, which is different from traditional chemotherapy that directly targets and kills cancer cells. SBRT is a highly precise form of radiation that targets tumors with minimal damage to surrounding tissues, potentially leading to fewer side effects. By combining these two methods, there's hope for a more effective and less harmful treatment option for patients with spinal tumors.

What evidence suggests that Pembrolizumab and radiosurgery could be effective for spinal tumors?

Research has shown that pembrolizumab, a type of immunotherapy, holds promise in treating tumors across various cancers. It helps the body's immune system fight cancer cells more effectively. Early studies suggest pembrolizumab could improve outcomes in very aggressive tumors. For spinal tumors, stereotactic body radiation therapy (SBRT) effectively controls tumor growth, with success rates between 80% and 96% after one year. SBRT also relieves pain for many patients. In this trial, participants will receive a combination of pembrolizumab and SBRT to explore whether this combination might enhance these benefits. More research is needed to understand how well this combination works for spinal tumors. ^{6 7 8 9 10}

Who Is on the Research Team?

Christina K Cramer, MD

Principal Investigator

Wake Forest Baptist Health Sciences

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a confirmed cancer diagnosis affecting the spine, who have an expected lifespan of at least 3 months. They should be eligible for radiation therapy and pembrolizumab treatment, and may already be on or scheduled to start pembrolizumab soon. Excluded are those with contraindications to pembrolizumab, other ongoing trials, symptomatic brain metastases that affect neurological assessments, severe illnesses or conditions that could interfere with the study, pregnant women, prior treatments to the lesion area, certain types of tumors like lymphoma or multiple myeloma.

Inclusion Criteria

I am currently being treated with pembrolizumab or will start within six weeks after my radiation therapy.

My cancer diagnosis has been confirmed by a pathology report.

My MRI shows epidural disease at 1 or 2 connected spine levels.

Exclusion Criteria

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

I do not have lymphoma, multiple myeloma, germinomas, seminomas, Wilm's tumors, or Ewing's sarcomas.

I have a specific type of spinal fracture.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive stereotactic body radiation therapy and at least one cycle of Pembrolizumab

6 months

MRI scans before treatment, 2 months after treatment, and 6 months after treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of pain relief, quality of life, and adverse events

6 months

Assessments at 1 month and 6 months after intervention

Long-term follow-up

Participants are monitored for long-term outcomes such as pain improvement and quality of life

Up to 20 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Stereotactic Body Radiation Therapy

Trial Overview The study investigates the combined effect of Stereotactic Body Radiation Therapy (a precise high-dose radiation treatment) and Pembrolizumab (an immunotherapy drug) on patients with advanced spinal cancer. The goal is to assess how well these treatments work together in controlling disease progression in the spine.

How Is the Trial Designed?

Group I: Stereotactic Body Radiotherapy and Pembrolizumab Treatment Experimental Treatment 3 Interventions

MRI scans of your spine (before treatment, 2 months after treatment, and 6 months after treatment) and immunotherapy with Pembrolizumab

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?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Published Research Related to This Trial

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 (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

A case study of a 52-year-old man with HIV and lung adenocarcinoma showed that combining pembrolizumab with stereotactic body radiotherapy led to serious immune-related adverse events, including massive pericardial effusion and interstitial pneumonia.

Despite initial treatment with pembrolizumab and radiotherapy, the patient's condition worsened, highlighting the need for caution and further clinical trials to assess the safety and efficacy of this combination therapy in HIV-infected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab combined with stereotactic body radiotherapy in a patient with human immunodeficiency virus and advanced non-small cell lung cancer: a case report. Li, D., He, C., Xia, Y., et al.[2018]

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, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

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]

In a study of 68 patients with advanced solid tumors, the combination of stereotactic body radiotherapy (SBRT) followed by pembrolizumab showed a high one-year treated metastasis control rate of 89.5%, indicating effective tumor response regardless of whether the tumors received complete or partial radiation coverage.

The study found that treated metastasis control (TMC) was significantly associated with improved overall survival, and SBRT altered tumor gene expression by increasing immune-related genes while decreasing those related to cell cycle and DNA repair, suggesting a mechanism for enhanced immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved Survival Associated with Local Tumor Response Following Multisite Radiotherapy and Pembrolizumab: Secondary Analysis of a Phase I Trial. Luke, JJ., Onderdonk, BE., Bhave, SR., et al.[2021]

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]

Citations

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NCT01295827 | Study of Pembrolizumab (MK-3475) in ... The study will investigate the safety, tolerability, and efficacy of pembrolizumab (2 mg/kg and 10 mg/kg) in participants with advanced or metastatic MEL.

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Efficacy Data for KEYTRUDA® (pembrolizumab) The most common adverse reactions (≥20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25 ...

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Spinal Metastases and the Evolving Role of Molecular ... Current literature is lacking in safety, efficacy, and estimates of overall response rates from the use of many of the new treatment agents when ...

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Merck Announces Phase 3 Trial of Subcutaneous ... Additionally, secondary endpoints of efficacy and safety were generally consistent for subcutaneous pembrolizumab administered with chemotherapy ...

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Safety and Clinical Activity of Pembrolizumab and Multisite ... Safety and clinical activity of pembrolizumab and multisite stereotactic body radiotherapy in patients with advanced solid tumors.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03924869

NCT03924869 | Efficacy and Safety Study of Stereotactic ... The purpose of this study is to assess the efficacy and safety of stereotactic body radiotherapy (SBRT) plus pembrolizumab (MK-3475) in the treatment of adult ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0959804924009201

Safety of combined ablative radiotherapy and immune ... We conclude that multi-site SBRT and ICI can be safely co-administered when SBRT is delivered with prioritization of normal tissue constraints.

10. advancesradonc.com advancesradonc.com/article/S2452-1094(23)00008-8/fulltext

Effect of Immunotherapy and Stereotactic Body ... This study aimed to investigate whether sequencing of IT and SBRT was associated with differences in local control (LC), overall survival (OS), and toxicity