Evaluating Combination Immunotherapy for Advanced Cholangiocarcinoma With Pembrolizumab and PEG-Intron

Advanced Cholangiocarcinoma Clinical Trial

Official title: A Phase II Multi-center Study Evaluating Combination Immunotherapy for Advanced Cholangiocarcinoma With Pembrolizumab and Sylatron (Peginterferon Alfa-2b) HCRN:GI16-263

Status Terminated

Clinical Trial Summary

This is an open-label, single-arm, multicenter Phase II safety and efficacy study of combination therapy with pembrolizumab and Sylatron (Peginterferon alpha-2b) in patients with advanced cholangiocarcinoma who have progressed on or cannot tolerate frontline chemotherapy.

Clinical Trial Description

Pembrolizumab and Sylatron Administration:

Pembrolizumab has been evaluated at 2 mg/kg every 3 weeks (Q3W), 10 mg/kg Q3W, or 10 mg/kg Q2W in multiple previous studies for different types of cancer, the response rate at higher dose level seems not improved compared to that of lower dose level. With concerns of increased toxicities from the combination pembrolizumab and sylatron therapy, the pembrolizumab dose is selected to be 200mg administered every three weeks. The approved dose of sylatron for melanoma is induction treatment at 6 μg/kg/week for 8 doses followed by 5 year of maintenance treatment at 3 μg/kg/week for up to 5 years. The approved dose of sylatron for chronic hepatitis C infection in combination with ribavirin is 1.5μg/kg weekly for 24 to 48 weeks.

Each cycle = 21 days or 3 weeks. Based on the approved dosage of sylatron, we decided to treat patients at 200mcg weekly up to 12 weeks (3 weeks as single agent, and 9 weeks in combination of pembrolizumab). Sylatron will start Cycle 1 Day 1 and continue on a weekly basis. We have prepared to reduce the dose of sylatron to 120mcg weekly, or 60mcg weekly if patients experience unacceptable toxicities at the higher dose level of sylatron.

Pembrolizumab will be administered intravenously as a 30 minute infusion at a dose of 200 mg every 3 weeks starting Week 4. Pembrolizumab will start Cycle 2 Day 1 and continue every 3 weeks. All trial treatments will be administered on an outpatient basis.

Sites should make every effort to target infusion timing to be as close to 30 minutes as possible. However, given the variability of infusion pumps from site to site, a window of -5 minutes and +10 minutes is permitted (i.e., infusion time is 30 minutes: -5 min/+10 min).

With concerns about toxicity while using long-term sylatron, if no additional benefit is seen beyond 12 weeks of treatment on top of that expected from pembrolizumab alone, patients will discontinue sylatron treatment after they have received 12 weeks of this therapy (3 weeks as single agent and 9 weeks in combination with pembrolizumab). Pembrolizumab should be continued in the absence of unacceptable toxicity (based on CTCAE v4) until disease progression-based on RECIST 1.1. In patients who had responded to the combination therapy, when patient shows disease progression while on single agent pembrolizumab treatment, Sylatron may be resumed at the discretion of the site investigator after discussion with the sponsor-investigator. ;

Related Conditions & MeSH terms

• Advanced Cholangiocarcinoma
• Cholangiocarcinoma

• NCT number: NCT02982720
• Study type: Interventional
• Source: Hoosier Cancer Research Network
• Status: Terminated
• Phase: Phase 2
• Start date: July 5, 2017
• Completion date: February 9, 2018