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

10 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to find out what effects (good and bad) Pembrolizumab and radiosurgery have on participants with high-grade epidural disease of the spine.

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.

What data supports the effectiveness of the treatment Pembrolizumab + Spine Radiosurgery for Spinal Tumors?

Pembrolizumab, a drug that helps the immune system fight cancer, has shown positive results in treating various cancers like lung cancer and melanoma. When combined with stereotactic body radiotherapy (a precise form of radiation therapy), it has improved outcomes in some cancer patients, suggesting potential benefits for spinal tumors as well. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and spine radiosurgery generally safe for humans?

Pembrolizumab, also known as Keytruda, is generally safe but can cause some side effects. Rarely, it may lead to type 1 diabetes in 0.2% of cases and pneumonitis (lung inflammation) in 1%-5% of patients. Common side effects include fatigue, cough, nausea, and rash. ^{1 2 6 7 8}

How is the treatment of Pembrolizumab combined with spine radiosurgery unique for spinal tumors?

This treatment is unique because it combines pembrolizumab, an immune system-boosting drug that helps T cells attack cancer, with precise radiation therapy (stereotactic body radiation therapy) to target spinal tumors, potentially enhancing the effectiveness of both treatments. ^{1 2 3 5 6}

Research Team

Christina K Cramer, MD

Principal Investigator

Wake Forest Baptist Health Sciences

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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, 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]

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]

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 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]

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 (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 (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]

References

1. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

2. United States pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Improved Survival Associated with Local Tumor Response Following Multisite Radiotherapy and Pembrolizumab: Secondary Analysis of a Phase I Trial. [2021]

4. England 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. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]

6. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. [2021]