Pembrolizumab + Spine Radiosurgery for Spinal Tumors
Recruiting in Palo Alto (17 mi)
Overseen byChristina K Cramer, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
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
Breakthrough Therapy
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.
12345Is 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.
12678How 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.
12356Eligibility 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.
+6 more
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.
+6 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Stereotactic Body Radiotherapy and Pembrolizumab TreatmentExperimental Treatment3 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Wake Forest Baptist Comprehensive Cancer CenterWinston-Salem, NC
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Who Is Running the Clinical Trial?
Wake Forest University Health SciencesLead Sponsor
References
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.
Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]Pembrolizumab (Keytruda; Merck Sharp & Dohme) is a humanized IgG4 monoclonal antibody used in cancer immunotherapy. It targets the programmed cell death-1 (PD-1) receptor, which is important in maintaining self-tolerance. However, immune checkpoint blockade is associated with a risk for immune-related adverse events (irAEs) potentially affecting the endocrine organs. Type 1 diabetes mellitus is a rare irAE of PD-1 inhibitors, occurring in 0.2% of cases.
Improved Survival Associated with Local Tumor Response Following Multisite Radiotherapy and Pembrolizumab: Secondary Analysis of a Phase I Trial. [2021]Multisite stereotactic body radiotherapy followed by pembrolizumab (SBRT+P) has demonstrated safety in advanced solid tumors (ASTs). However, no studies have examined the relationships between irradiated tumor response, SBRT-induced tumor gene expression, and overall survival (OS).
Pembrolizumab combined with stereotactic body radiotherapy in a patient with human immunodeficiency virus and advanced non-small cell lung cancer: a case report. [2018]Pembrolizumab has significantly improved outcomes in patients with advanced non-small cell lung cancer. Combining programmed death-1 inhibitor with stereotactic body radiotherapy showed a slight toxicity and good benefits in recent clinical trials. However, patients infected with human immunodeficiency virus were excluded from most trials because it was assumed that their anti-tumor immunity was compromised compared with immunocompetent patients.
Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]Pembrolizumab (MK-3475) is a monoclonal antibody that binds to the PD-1 receptor on T cells and prevents binding to its ligands PD-L1 and PD-L2. Blocking this receptor frees T cells from the inhibitory effects of PD-L1 and allows them to mediate antitumor effects against cancer cells. In a large Phase I study of 411 patients with melanoma, high durable response rates over a range of doses and schedules have been shown with very little toxicity. A Phase III study of pembrolizumab comparing two schedules of administration with the current standard treatment with the anti-CTLA-4 monoclonal antibody is in progress. Combinations with other checkpoint inhibitors as well as other anticancer agents are also being evaluated. Approval of pembrolizumab for the treatment of melanoma is expected.
Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]Pembrolizumab (Keytruda) is a monoclonal antibody against the programmed cell death-1 (PD-1) receptor on lymphocytes, which is one of the immune checkpoint inhibitors (ICIs) approved for multiple solid and hematologic malignancies. Although ICIs have proven to be more effective and less toxic compared to chemotherapy, there are reports of adverse side effects with ICIs. For example, pneumonitis is a potentially lethal side effect occurring in 1%-5% of patients who received ICIs in clinical trials, and there are case reports with clinical and radiological features of checkpoint inhibitor-pneumonitis (CIP).
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating phase 1 trial. The overall response rate (ORR) by blinded independent central review per RECIST v1.1 was 24% (95% confidence interval, 15-34); with 6 months of follow-up, 86% of responses were ongoing. The most common (≥20%) adverse reactions were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. The benefits of the observed ORR with prolonged duration of responses outweighed the risks of immune-mediated adverse reactions in this life-threatening disease and represented an improvement over available therapy. Important regulatory issues in this application were role of durability of response in the evaluation of ORR for accelerated approval, reliance on data from a first-in-human trial, and strategies for dose selection. Clin Cancer Res; 23(19); 5666-70. ©2017 AACR.
Pembrolizumab: first global approval. [2021]Pembrolizumab [Keytruda(®) (US)], a humanized monoclonal antibody against the programmed death receptor-1 (PD-1) protein, has been developed by Merck & Co for the treatment of cancer. Pembrolizumab has received its first global approval for the treatment of advanced, unresectable or metastatic malignant melanoma in the US, for use in patients with disease progression after prior treatment with ipilimumab and, for BRAF V600 mutation-positive patients, a BRAF inhibitor. It is the first anti-PD-1 therapy to receive regulatory approval in the US, and is currently under regulatory review in the EU. This article summarizes the milestones in the development of pembrolizumab leading to this first approval for the treatment of malignant melanoma.