Yttrium-90 Radioembolization + Nivolumab for Liver + Extra-hepatic Metastases From Colorectal Cancer

NCT03307603 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: CASE3216
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study has two portions. The main goal of the Phase Ib portion of this research study is to see at what time Yttrium-90 (Y-90) radioembolization therapy and nivolumab can safely be given to patients without having too many side effects. Other purposes of this research study will be to study any tumor responses. The Phase II portion of the study will test how many patients show shrinkage in their tumor with this combination of medicines and what changes occur inside the cancer cells and blood cells after treatment. The study team will pick the part of the study each subject participates in. Y-90 radioembolization therapy is minimally invasive procedure that combines two types of therapy (embolization which blocks certain blood vessels, and radiation therapy, which kills cancer cells) to treat cancer tumors in the liver. This works with tiny glass or resin beads filled with the radioactive isotope yttrium-90 (Y-90). They are placed inside the blood vessels that feed the tumor in the liver. This blocks the supply of blood to the cancer cells and delivers a high dose of radiation to the tumor while sparing normal tissue. Nivolumab is an FDA approved medicine that is used for the treatment of different types of cancers and metastases (second growths from cancer).

Conditions

Metastatic Colorectal Cancer

Keywords

Yttrium-90 radioembolization; Nivolumab

Outcome Measures

Primary Outcomes (2)

• Phase I: Average number of serious adverse events experience by patients

  assessed by CTCAE version 4 of nivolumab in combination with Y-90 radioembolization when administered to patients with metastatic colorectal cancer who have hepatic metastases appropriate for treatment with Y-90 radioembolization therapy.

  Up to 2 years after starting study

• Phase II: Response rate

  assessed by RECIST 1.1 criteria of metastases outside of the Y-90 radioembolization treatment field in patients with metastatic colorectal cancer who undergo Y-90 radioembolization therapy to hepatic metastases followed by nivolumab.

  Up to 2 years after starting study

Secondary Outcomes (4)

• Phase I: Progression free survival (PFS)

  Up to 2 years after starting study

• Phase I: Overall survival

  Up to 2 years after starting study

• Phase II: Progression free survival (PFS)

  Up to 2 years after starting study

• Phase II: Overall survival

  Up to 2 years after starting study

Study Arms (1)

Yttrium-90 + Nivolumab

EXPERIMENTAL

240 mg Nivolumab intravenously, beginning at 2 weeks after Yttrium-90 treatment and given every 2 weeks until progression or toxicity. Additional dose at 2 weeks prior to Y-90 will be given if the first 3 patients do not have toxicity. If any of the first 3 patients have toxicity, the schedule can be relaxed to begin 3 weeks after Y-90 treatment.

Radiation: yttrium-90 radioembolization; Drug: Phase Ib - nivolumab; Drug: Phase II - nivolumab

Interventions

yttrium-90 radioembolization RADIATION

Yttrium-90 will be given as biocompatible resin-based microspheres and will be introduced to the tumor(s) on one side of the liver through a catheter placed in the right or left hepatic artery. The dose of radiation will be determined by a radiologist and will be based on body surface area and tumor burden.

Yttrium-90 + Nivolumab

Phase Ib - nivolumab DRUG

240 mg intravenously

Yttrium-90 + Nivolumab

Phase II - nivolumab DRUG

nivolumab will be administered as determined during the phase Ib portion of the study. Nivolumab will be administered on an every 2 week basis for a total of 48 weeks or until disease progression, unacceptable toxicity or discontinuation due to patient/physician preference.

Yttrium-90 + Nivolumab

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed metastatic colorectal cancer.
• Patients must have liver metastases and be appropriate for treatment with Y-90 radioembolization therapy as determined by the treating medical oncologist and interventional radiologist. Prior Y-90 therapy is not permitted.
• Patients must have measurable disease that is located outside of the Y-90 radioembolization field.
• Patients must have a metastatic focus amenable to biopsy that is located outside of the Y-90 radioembolization field. It is permissible to use the same lesion for biopsy as for assessment to tumor response.
• Patients must have received at least one line of prior chemotherapy and must have had resolution of all side effects to at least at Grade 1 prior to trial entry.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Patients must have normal organ and marrow function as defined below:
• Hemoglobin ≥ 9.0 g/dl
• Leukocytes ≥ 2,000/mcL
• Absolute neutrophil count ≥ 1,500/mcL
• Platelet count ≥ 100,000/mcL
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (except in patients with Gilbert Syndrome, who can have a total bilirubin \< 3.0 mg/dL)
• Aspartate aminotransferase (AST) (SGOT) ≤ 3 X institutional upper limit of normal
• Alanine aminotransferase (ALT) (SGPT) ≤ 3 X institutional upper limit of normal
• Serum creatinine ≤ 1.5 X ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below):

You may not qualify if:

• Patients with ongoing toxicities \> grade 1 according to NCI CTCAE Version 4.0 (excluding alopecia and neuropathy) due to prior anti-cancer therapy.
• Patients receiving any other investigational agent or active chemotherapy.
• Patients who have previously been treated an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-Cytotoxic T-lymphocyte associated protein (CTLA)-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
• Patients with a known autoimmune disease. Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
• Patients having a condition requiring systemic treatment with either corticosteroids (\> 10 mg/day prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg/day prednisone equivalents are permitted in the absence of active autoimmune disease.
• Patients who are positive for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection.
• Patients with a known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• Patients who have received prior external beam radiation therapy to the liver.
• Patients who have clinical evidence of ascites or are in clinical liver failure.
• Patients who are known to have greater than 20% lung shunting of the hepatic artery blood flow determined by Technetium microaggregated albumin (MAA) scan (if conducted prior to study enrollment).
• Patients who have had a standard of care pre-assessment angiogram that demonstrates abnormal vascular anatomy that would result in significant reflux of hepatic arterial blood to the stomach, pancreas or bowel.
• Patients with known portal vein thrombosis.
• Patients with untreated brain metastases or leptomeningeal metastases will be excluded. Patients with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for at least 4 weeks after treatment is complete and within 28 days prior to the first dose of nivolumab administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (\> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
• Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients who are pregnant or breastfeeding will be excluded from the study due to the potential teratogenic or abortifacient effects that may result from nivolumab or Y-90 Theraspheres. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with nivolumab and Y-90, breastfeeding should be discontinued if the mother is treated with nivolumab and Y-90. These potential risks may also apply to other agents used in this study.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

MeSH Terms

Conditions

Colorectal Neoplasms

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

Study Officials

• Jennifer Eads, MD

  University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

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: September 7, 2017
• First Posted: October 11, 2017
• Study Start: December 1, 2018
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2021
• Last Updated: February 27, 2018

Record last verified: 2018-02