PI Pembro in Combination With Stereotactic Body Radiotherapy for Liver Metastatic Colorectal Cancer

NCT02837263 | Completed Phase 1 Results DMC

• 6 other identifiers: UW15063NCI-2016-010772016-0303A534260SMPH\MEDICINE\HEM-ONCProtocol Version 7/12/2018
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Recurrence Rate at 1 Year

  Determine the recurrence rate at 1 year following clearance of metastatic disease in the setting of treatment with SBRT and pembrolizumab

  1 year

Secondary Outcomes (3)

• Time to Recurrence Estimated Using the Kaplan-Meier Method

  up to 6 years

• Disease-free Survival Estimated Using the Kaplan-Meier Method

  up to 6 years

• Overall Survival Estimated Using the Kaplan-Meier Method

  up to 6 years

Other Outcomes (3)

• PET/MR Imaging Parameters

  1 year

• Tumor-infiltrating Lymphocytes

  1 year

• Expression Levels of PDL1

  1 year

Study Arms (1)

SBRT + Pembrolizumab

EXPERIMENTAL

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); Drug: Pembrolizumab

Interventions

Stereotactic body radiotherapy (SBRT) RADIATION

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.

Also known as: Stereotactic Body Radiation Therapy

SBRT + Pembrolizumab

Pembrolizumab DRUG

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 ipiliumumab and, if BRAF V600 mutation positive, a BRAF inhibitor.

Also known as: Pembro, Keytruda

SBRT + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Have measurable disease based on RECIST 1.1
• Fresh or archived colorectal cancer tissue, preferably from a hepatic metastatic site. Archival tissue is acceptable for enrolled into this study. Participants who have no archival tissue available do not need to undergo a new biopsy solely for the purpose of this study
• Participants must have received at least one prior line or chemotherapy including an irinotecan or oxaliplatin-fluoropyrimidine-based systemic treatment for colorectal cancer
• Have performance status of 0 or 1 on the ECOG Performance Scale
• Demonstrate an adequate organ function as defined in Table 1. These labs should be repeated if not completed within 10 days of SBRT treatment initiation

You may not qualify if:

• 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.)
• Participant has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Participant has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously resected brain metastases may participate provided it has been at least 6 months and no CNS progression has been identified.
• Participant has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Participant has known history of, or any evidence of active, non-infectious pneumonitis.
• Participant has an active infection requiring systemic therapy.

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Related Links

• UW Carbone Cancer Center Home Page

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Radiosurgery; pembrolizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Dustin Deming, MD
• Organization: UW Carbone Cancer Center

ddeming@medicine.wisc.edu

(608) 265-1042

Study Officials

• Dustin Deming

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2016
• First Posted: July 19, 2016
• Study Start: August 11, 2016
• Primary Completion: November 2, 2021
• Study Completion: May 31, 2023
• Last Updated: May 1, 2026
• Results First Posted: May 1, 2026

Record last verified: 2026-04

Locations

US (1)