Pembrolizumab in Combination With Stereotactic Body Radiotherapy for Liver Metastatic Colorectal Cancer

University of Wisconsin, Madison2 sites in 1 country15 target enrollmentAugust 11, 2016

ConditionsColorectal Cancer Colorectal Adenocarcinoma Stage IVA Colorectal Cancer Stage IVB Colorectal Cancer Metastatic Carcinoma in the Liver

InterventionsStereotactic body radiotherapy (SBRT)Pembrolizumab

DrugsPembrolizumab

Overview

Phase: Phase 1
Intervention: Stereotactic body radiotherapy (SBRT)
Conditions: Colorectal Cancer
Sponsor: University of Wisconsin, Madison
Enrollment: 15
Locations: 2
Primary Endpoint: Recurrence rate at 1 year
Status: Completed
Last Updated: yesterday

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Detailed Description

This is a phase 1b feasibility study to evaluate the use of PD-1 blockade in combination with ablative radiotherapy for the treatment of metastatic colorectal cancer (CRC). This study will examine the sequential combination of stereotactic body radiotherapy (SBRT) and pembrolizumab for patients for whom the goal is eradicating all known sites of disease. It is very likely that for many patients the SBRT therapy will be completed following other modalities including operative resection or ablation.

Registry

clinicaltrials.gov

Start Date

August 11, 2016

End Date

May 31, 2023

Last Updated

yesterday

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

University of Wisconsin, Madison

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Willing and able to provide written informed consent/assent for the trial
•Be \>/= 18 years of age on day of signing consent.
•Have a diagnosis of histologically confirmed metastatic colorectal cancer to the liver (no other sites of metastatic disease)
•\* Histologic confirmation of a colorectal primary tumor is acceptable if accompanied by radiographic evidence of metastatic disease
•Tumor must be mismatch repair (MMR) proficient as determined by microsatellite instability or immunohistochemistry for for MMR proteins
•Microsatellite instability testing must be MSI-stable or MSI-low
•Or IHC for MMR proteins must demonstrate intact MMR proteins
•Participant must be candidate for SBRT to at least one intrahepatic lesion. There is no limit on the number of intrahepatic lesions the patient may have
•Participant must be a surgical candidate with therapeutic goal of eradicating all known disease with one additional surgery. Portal venous embolization is permitted to ensure resectability.
•Prior resection of extra-hepatic metastatic disease allowed if completed more than 12 months previous to study enrollment and now new extra-hepatic disease has been found

Exclusion Criteria

•Current participation and receiving study therapy or previous participation in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the initiation of SBRT
•Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 (first day of SBRT treatment) or who has not recovered (i.e. \< Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
•Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e. \< Grade 1 or at baseline) from adverse events due to a previously administered agent. Prior radiotherapy to the liver is not allowed
•Participants with \< Grade 2 neuropathy are an exception to this criterion and may qualify for the study
•If the participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
•Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the initiation of SBRT
•Participant has a known history of active TB (Bacillus Tuberculosis)
•Hypersensitivity to pembrolizumab or any of its excipients
•Participant has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 (first day or SBRT treatment) or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
•Participant has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Prior radiotherapy to the liver is not allowed. (Notes: Participants with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.)

Arms & Interventions

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).

Intervention: Stereotactic body radiotherapy (SBRT)