This is a single arm phase 2 study of Single Tremelimumab with Regular Interval Durvalumab (STRIDE) plus Gemcitabine and Cisplatin (GEMCIS) in locally advanced unresectable/metastatic combined hepatocellular-cholangiocarcinoma (cHCC-CCA). Cycles 1 through 8 will be in 3 week intervals and Cycles 9+ will be in 4 week intervals. Tremelimumab is administered at 300mg intravenously once at Cycle 1. Durvalumab is administered at 1500mg intravenously every 3 weeks for Cycles 1-8, then every 4 weeks for Cycles 9+. Gemcitabine is administered at 1000mg/m\^2 intravenously on Day 1 and Day 8 of Cycles 1-8 only. Cisplatin is administered at 25mg/m\^2 intravenously on Day 1 and Day 8 of Cycles 1-8 only. Subjects will require a visit with appropriate laboratory work prior to the start of each cycle. Disease assessment will occur at screening and then every 9 weeks until the end of Cycle 9. Disease assessments will then occur every 8 weeks. Subjects will continue treatment until progression per RECIST 1.1, toxicity or subject/physician decision. A maximum of 24 months treatment from Cycle 1 Day 1 is allowed.
Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act in the US, European Union [EU] Data Privacy Directive in the EU) obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations. Informed written consent must be ≤ 28 days prior to registration.
Age ≥ 18 years at the time of registration.
Body weight > 30 kg.
Histological or cytological confirmation of combined hepatocellular-cholangiocarcinoma. NOTE: Locally advanced unresectable/metastatic.
History of myocardial infarction ≤ 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.
Participation in another clinical study with an investigational product ≤ 28 days prior to registration unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
Liver directed therapy (TACE, Y-90, liver directed radiation) ≤ 28 days prior to registration. NOTE: Prior liver directed therapy > 28 days of registration is allowed as long as the subject has at least one measurable untreated lesion by RECIST v.1.1.
Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
Single group
Tremelimumab
DrugTremelimumab is administered at 300mg intravenously once at Cycle 1.
Durvalumab
DrugDurvalumab is administered at 1500mg intravenously every 3 weeks for Cycles 1-8, then every 4 weeks for Cycles 9+.
Gemcitabine
DrugGemcitabine is administered at 1000mg/m\^2 intravenously on Day 1 and Day 8 of Cycles 1-8 only.
Cisplatin
DrugCisplatin is administered at 25mg/m\^2 intravenously on Day 1 and Day 8 of Cycles 1-8 only.
Confirmed objective response rate (ORR)
ORR will include confirmed complete response (CR) + confirmed partial response (PR) and will be determined as per RECIST version 1.1. A confirmed response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart.
Overall Survival (OS)
OS is defined as the time from registration to death from any cause.
Progression-free survival (PFS)
PFS is defined as the time from registration to disease progression, as defined by RECIST 1.1, or until death, whichever occurs first.
Disease control rate (DCR)
Disease control is defined as achieving complete response (CR), partial response (PR), or maintaining stable disease (SD) for at least 4 months (at time of second scan) while on treatment. Objective status will be assessed using RECISTv1.1 criteria. The Evaluable Population will be used. Disease control rate will be calculated as the proportion of evaluable subjects who achieve disease control.
Adverse Event Rates
The Safety Population will be used for adverse event analyses according to the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v5. The rate of subjects experiencing at least one Grade 3+ adverse event (regardless of attribution) will be reported.
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Mehmet Akce
Lead sponsor
Hoosier Cancer Research Network
Sponsor institution
University of Alabama at Birmingham
Collaborator
AstraZeneca
Collaborator
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