A Phase II Study of Single Tremelimumab With Regular Interval Durvalumab Plus Gemcitabine and Cisplatin in Locally Advanced Unresectable/Metastatic Combined Hepatocellular-cholangiocarcinoma

NCT06855225 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCRN GI24-671
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Combined Hepatocellular and Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  24 months

Secondary Outcomes (4)

• Overall Survival (OS)

  24 months

• Progression-free survival (PFS)

  24 months

• Disease control rate (DCR)

  24 months

• Adverse Event Rates

  24 months

Study Arms (1)

Single Tremelimumab with Regular Interval Durvalumab plus Gemcitabine and Cisplatin

EXPERIMENTAL

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.

Drug: Tremelimumab; Drug: Durvalumab; Drug: Gemcitabine; Drug: Cisplatin

Interventions

Durvalumab DRUG

Durvalumab is administered at 1500mg intravenously every 3 weeks for Cycles 1-8, then every 4 weeks for Cycles 9+.

Also known as: Imfinzi

Single Tremelimumab with Regular Interval Durvalumab plus Gemcitabine and Cisplatin

Gemcitabine DRUG

Gemcitabine is administered at 1000mg/m\^2 intravenously on Day 1 and Day 8 of Cycles 1-8 only.

Also known as: Gemzar

Single Tremelimumab with Regular Interval Durvalumab plus Gemcitabine and Cisplatin

Cisplatin DRUG

Cisplatin is administered at 25mg/m\^2 intravenously on Day 1 and Day 8 of Cycles 1-8 only.

Also known as: Platinol

Single Tremelimumab with Regular Interval Durvalumab plus Gemcitabine and Cisplatin

Tremelimumab DRUG

Tremelimumab is administered at 300mg intravenously once at Cycle 1.

Also known as: Imjudo

Single Tremelimumab with Regular Interval Durvalumab plus Gemcitabine and Cisplatin

Eligibility Criteria

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

You may qualify if:

• 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.
• Measurable disease according to RECIST 1.1. NOTE: See Section 9 for additional details.
• Must have life expectancy ≥ 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 28 days prior to registration.
• Adequate organ and marrow function as defined below. All screening labs to be obtained ≤ 28 days prior to registration.
• Absolute neutrophil count (ANC) ≥ 1,500/mm3
• Platelet count ≥ 100,000/mm3
• Hemoglobin ≥ 9.0 g/dL
• Total Bilirubin ≤ 1.5 x upper limit of normal (ULN). NOTE: This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician and with a Total Bilirubin \< 3 x ULN.
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 2. 5 x ULN unless liver metastases are present, in which case it must be ≤ 5 x ULN
• PT and INR and aPTT ≤ 1.5 x ULN. NOTE: If patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy subject is eligible.
• Creatinine ≤ 1.5 x ULN or Calculated creatinine clearance must be ≥ 50 mL/min using the Cockcroft-Gault formula.

You may not qualify if:

• 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.
• Subjects with Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the sponsor-investigator.
• Subjects with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the sponsor-investigator.
• Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment other than the study drugs. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• Prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment.
• Subjects who have received prior gemcitabine, cisplatin, anti-PD-1, anti-PD-L1 or anti-CTLA-4 for locally advanced or metastatic disease. NOTE: Prior anti-PD-1, anti-PD-L1 or anti-CTLA-4 can be allowed if it was administered for nonmetastatic and early stage disease, in that case subject:
• Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
• All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study.
• Must not have experienced a ≥ Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE: Subjects with endocrine AE of ≤ Grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.
• Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of \> 10 mg prednisone or equivalent per day.
• Current or prior use of immunosuppressive medication ≤ 14 days prior to registration. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
• Systemic corticosteroids at physiologic doses not to exceed \<\<10 mg/day\>\> of prednisone or its equivalent

Sponsors & Collaborators

• Mehmet Akce: lead
• AstraZeneca: collaborator
• University of Alabama at Birmingham: collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Conditions

Liver Neoplasms

Interventions

tremelimumab; durvalumab; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Mehmet Akce, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mehmet Akce, MD

CONTACT

205-975-0832; makce@uabmc.edu

Ahran Lee

CONTACT

3176345842; alee@hoosiercancer.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-investigator

Study Record Dates

• First Submitted: February 25, 2025
• First Posted: March 3, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: April 17, 2026

Record last verified: 2026-04

Locations

US (1)