NCT03507699

Combined Immunotherapy and Radiosurgery for Metastatic Colorectal Cancer

Combination Treatment of Nivolumab, Ipilimumab, Intratumoral CMP-001 and Radiosurgery for Liver Metastases in Colorectal Carcinoma

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 19 (actual)
• Sponsor: Sheba Medical Center · Other Government
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

A single institution study to evaluate the safety and tolerability of the combination treatment of nivolumab, ipilimumab, CMP-001 and radiosurgery in patients with metastatic colorectal cancer with liver metastases.

Detailed description

Patients will be treated with radiosurgery to liver metastases (completed by day 1), followed by a priming dose of subcutaneous CMP-001 (day 1 ± 4 days), intratumoral injections of CMP-001 on days 13, 36 and 55, combined with nivolumab 3mg/kg every 2 weeks (start day 15) and ipilimumab 1 mg/kg every 6 weeks (start day 15). From day 71 biweekly subcutaneous injections of CMP-001 will commence. Nivolumab, ipilimumab and subcutaneous injections of CMP-001 will be continued until disease progression or up to 24 months in the absence of disease progression or unacceptable toxicity. Two research biopsies will be taken from a liver metastasis. The first biopsy will be taken during the screening period (pretreatment) and the second one 5 weeks post-radiosurgery (which is 3 weeks post-initiation of nivolumab / ipilimumab). As a safety run-in, the initial cohort of 3-6 patients will not receive radiosurgery. The next cohort will not commence until the last patient from the initial cohort has been followed up for at least 8 weeks post first intratumoral injection. Efficacy endpoints will be based upon a non-irradiated lesion.

Conditions

• Colorectal Neoplasms Malignant
• Liver Metastases

Interventions

Type	Name	Description
RADIATION	Liver radiation therapy	21 Gy in three fractions to one liver metastasis
DRUG	Nivolumab Injection [Opdivo]	administered IV at a dose of 3mg/kg every 2 weeks
DRUG	Ipilimumab Injection [Yervoy]	administered IV at a dose of 1mg/kg every 6 weeks
DRUG	CMP-001	A TLR9 agonist, will be administered both into the liver metastasis (three times), and also injected subcutaneously at a dose of 5-10 mg every two weeks.

Timeline

• Start date: 2018-12-15
• Primary completion: 2021-08-18
• Completion: 2022-05-25
• First posted: 2018-04-25
• Last updated: 2023-04-18

Locations

1 site across 1 country: Israel

Regulatory

• FDA-regulated drug study