PI Pembro in Combination With Stereotactic Body Radiotherapy for Liver Metastatic Colorectal Cancer
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|ClinicalTrials.gov Identifier: NCT02837263|
Recruitment Status : Active, not recruiting
First Posted : July 19, 2016
Last Update Posted : December 14, 2020
The purpose of this research study is:
- To find out how safe the study drug, pembrolizumab, is when combined with stereotactic body radiotherapy (SBRT) to the liver.
- To see how well subjects can tolerate treatment with pembrolizumab and SBRT.
- To find out how often colorectal cancer comes back 1 year after surgically removing all known disease and being treated with SBRT and pembrolizumab.
|Condition or disease||Intervention/treatment||Phase|
|Colorectal Cancer Colorectal Adenocarcinoma Stage IVA Colorectal Cancer Stage IVB Colorectal Cancer Metastatic Carcinoma in the Liver||Radiation: Stereotactic body radiotherapy (SBRT) Drug: Pembrolizumab||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pembrolizumab in Combination With Stereotactic Body Radiotherapy for Liver Metastatic Colorectal Cancer|
|Actual Study Start Date :||August 11, 2016|
|Estimated Primary Completion Date :||June 2021|
|Estimated Study Completion Date :||June 2022|
Experimental: SBRT + Pembrolizumab
Subjects will receive stereotactic body radiotherapy (SBRT) within 4 weeks of enrollment. Following SBRT, subjects will receive one cycle of pre-operative pembrolizumab given as an IV over approximately 30 minutes. Surgical management to remove all known sites of metastatic disease should occur 2 weeks post pembrolizumab treatment. Approximately 4-8 weeks after surgery subjects will being the second phase of pembrolizumab treatment. They will receive this treatment every 3 weeks (cycle) for 8 more cycles after surgery. Prior to the 5th cycle of pembrolizumab subjects will also have tumor imaging (CT or MRI).
Radiation: Stereotactic body radiotherapy (SBRT)
SBRT treatment will consist of 40-60 Gy delivered in five fractions prescribed to the planning target volume (PVT). Image guidance with MRI, megavoltage CT or cone beam CT scans would be required.
SBRT will be initiated on Day 0. This should be initiated within 4 weeks of signing informed consent. An additional 2 weeks will be allowed if necessary due to SBRT treatment planning.
Other Name: Stereotactic Body Radiation Therapy
Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. KeytrudaTM (pembrolizumab) has recently been approved in the United Stated for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilumumab and, if BRAF V600 mutation positive, a BRAF inhibitor.
- Recurrence rate at 1 year [ Time Frame: 1 year ]Determine the recurrence rate at 1 year following clearance of metastatic disease in the setting of treatment with SBRT and pembrolizumab
- Time to recurrence estimated using the Kaplan-Meier method [ Time Frame: 1 year ]The 95% confidence of the median time to recurrence will be calculated using the Brookmeyer-Crowley method
- Disease-free survival estimated using the Kaplan-Meier method [ Time Frame: 1 year ]The 95% confidence of the median time to disease free survival calculated using the Brookmeyer-Crowley method.
- Overall survival estimated using the Kaplan-Meier method [ Time Frame: 1 year ]The 95% confidence of the median time to overall survival calculated using the Brookmeyer-Crowley method.
- PET/MR imaging parameters [ Time Frame: 1 year ]Imaging biomarkers (SUVtot, SUVmean, SUVmax) will be summarized using standard descriptive statistics in terms of means, standard deviations, medians, and ranges. Percentage changes in imaging biomarkers will be calculated between assessment time points. Logistic regression analysis will be conducted to evaluate whether changes in imaging biomarkers predict the recurrence rate at 1 year following clearance of metastatic disease.
- Tumor-infiltrating lymphocytes [ Time Frame: 1 year ]The number of tumor-infiltrating lymphocytes will be summarized in terms of means and standard deviations for each assessment time point. A negative binomial regression or overdispersed Poisson regression model with patient specific random effects will be used to evaluate changes in the number of tumor-infiltrating lymphocytes.
- Expression levels of PDL1 [ Time Frame: 1 year ]Linear regression analysis will be conducted to examine the correlation between expression levels of PDL1 in colorectal cancer (CRC) liver metastases.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02837263
|United States, Wisconsin|
|University of Wisconsin Carbone Cancer Center|
|Madison, Wisconsin, United States, 53792|
|Principal Investigator:||Dustin Deming||University of Wisconsin, Madison|