Neoplasms

Symptoms and General Pathology

All Conditions

Digestive System Diseases

Neoplasm Metastasis

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neoplastic Processes

All Drugs and Chemicals

Antineoplastic Agents

Hematinics

Immunomodulating Agents

Durvalumab

Liver Extracts

Tremelimumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Antineoplastic Agents, Immunological

Immunologic Factors

Six patients will be enrolled in cohorts of three to be administered Y-90, SBRT, and Druvalumab.

Six patients will be enrolled in cohorts of three to be administered Y-90, SBRT, and Druvalumab + Tremelimumab.

Durvalumab will be dosed at 1500 mg fixed dosing every 4 weeks and continued at this interval until progression or dose-limiting toxicity.

Durvalumab will be dosed at 1500 mg fixed dosing every 4 weeks and continued at this interval until progression or dose-limiting toxicity. Tremelimumab will be dosed at 75 mg every 4 weeks (same day as durvalumab infusion) for a maximum of 4 doses.

Durvalumab and Tremelimumab

Yttrium-90 microsphere therapy consists of resin beads loaded with Yttrium, a pure beta emitter with a 64.2 hour half-life. Radioembolization will be performed as standard of care therapy per current NCCN guidelines.

Y-90 Selective Internal Radiation Therapy (SIRT)

High-dose hypofractionated conformal external beam radiation therapy that is considered a standard of care. SBRT will also be considered for metastases that are persistent and/or progressive after Y-90 based on MR imaging and pathology from tissue biopsies.

Stereotactic Body Radiation Therapy (SBRT)

Karyn Goodman, MD

This study is evaluating the combination of Y-90 radioembolization followed by SBRT with the immunotherapy drugs, durvalumab and tremelimumab, to improve disease control of liver metastases for patients with microsatellite stable colorectal cancer.

The first 6 patients will receive durvalumab alone with Y-90 and SBRT followed by 4 months of durvalumab. The next 6 patients will received durvalumab with Y-90 and SBRT followed by 4 months of durvalumab + tremelimumab.Durvalumab will be dosed at 1500 mg fixed dosing every 4 weeks and continued at this interval until progression or dose-limiting toxicity. There will be no dose escalation. For patients who will receive both Durvalumab and Tremelimumab, the Tremelimumab will be dosed at 75 mg every 4 weeks (same day as durvalumab infusion) for a maximum of 4 doses. There will be no dose escalation.

Immunotherapy Combined With Y-90 and SBRT for Colorectal Liver Metastases

Phase I Study of Dual Immune Checkpoint Blockade (Anti-PD-L1 (Durvalumab) (MEDI4736) and Anti-CTLA4 (Tremelimumab) Plus Yttrium-90 (Y-90) Radioembolization & Stereotactic Body Radiation Therapy (SBRT) in Refractory Metastatic MSS (Microsatellite Stable) Colorectal Cancer With Liver Metastases

Adverse events related to Y-90, SBRT, and durvalumab plus tremelimumab will be summarized by dose and severity as assessed by the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0.

Defined as the rate of \>Grade 3 treatment-related adverse events during treatment or within 3 months of treatment completion.

The determination of antitumor activity will be based on objective response assessments as defined by RECIST version 1.1 and immune RECIST.

Measure of overall survival rate by examining the incidence of death over a two year period.

Measured by the percentage of viable tumor throughout and post treatment

Spots Global Cancer Trial Database for Immunotherapy Combined With Y-90 and SBRT for Colorectal Liver Metastases

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial