A Phase II Multi-center Study Evaluating Combination Immunotherapy for Advanced Cholangiocarcinoma With Pembrolizumab and Sylatron (Peginterferon Alfa-2b) HCRN:GI16-263
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Advanced Cholangiocarcinoma
- Sponsor
- Aiwu Ruth He, MD
- Enrollment
- 4
- Locations
- 1
- Primary Endpoint
- Asses Objective Response Rate (ORR) of All Patients Receiving Pembrolizumab and Sylatron Combination Therapy
- Status
- Terminated
- Last Updated
- 4 years ago
Overview
Brief 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.
Detailed 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.
Investigators
Aiwu Ruth He, MD
Sponsor-Investigator
Hoosier Cancer Research Network
Eligibility Criteria
Inclusion Criteria
- •Subject must meet all of the following applicable inclusion criteria to participate in this study:
- •Be willing and able to provide written informed consent/assent for the trial.
- •Be at least 18 years of age on day of signing informed consent.
- •Patients must have received 1 line of prior systemic therapy for metastatic or resectable disease (i.e. patients may have received adjuvant gemcitabine and then later gemcitabine/cisplatin for recurrent metastatic disease)
- •Histological confirmation of cholangiocarcinoma.
- •Have measurable disease based on RECIST 1.
- •Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day
- •Subjects for whom newly obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the sponsor-investigator.
- •Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
- •Demonstrate adequate organ function:
Exclusion Criteria
- •The subject must be excluded from participating in the trial if the subject:
- •A history of anaphylaxis to peginterferon alfa-2b or interferon alfa-2b
- •Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- •Has a known history of active Bacillus Tuberculosis (TB)
- •Hypersensitivity to pembrolizumab or any of its excipients.
- •Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- •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.
- •Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
- •Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
Arms & Interventions
Pembrolizumab and Sylatron
Pembrolizumab will be administered intravenously at a dose of 200 mg every 3 weeks starting week 4. Sylatron will be administered at a dose of 200mcg subcutaneously weekly starting at week 1.
Intervention: Pembrolizumab
Pembrolizumab and Sylatron
Pembrolizumab will be administered intravenously at a dose of 200 mg every 3 weeks starting week 4. Sylatron will be administered at a dose of 200mcg subcutaneously weekly starting at week 1.
Intervention: Sylatron
Outcomes
Primary Outcomes
Asses Objective Response Rate (ORR) of All Patients Receiving Pembrolizumab and Sylatron Combination Therapy
Time Frame: 12 months
Defined as the proportion of subjects who achieve the best response (CR and PR) determined by RECIST1.1
Secondary Outcomes
- Assess Progression Free Survival (PFS) of Patients Receiving Pembrolizumab and Sylatron(36 months)
- Asses Overall Survival (OS) of Patients Receiving Pembrolizumab and Sylatron(36 months)
- Assess Adverse Events, Serious Adverse Events and Serious Adverse Events Leading to Discontinuation of the Treatment (Death) of Combined Pembrolizumab and Sylatron Therapy.(36 months)
- Assess Objective Response Rate (ORR)(36 months)