HYPERION CCA: a Phase 2 Trial of Systemic Therapy With or Without Liver-directed Radiation Therapy for Patients With Advanced Intrahepatic Cholangiocarcinoma

NCT06858735 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2024-1816NCI-2025-01520
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This study will compare outcomes for M1 iCCA patients treated with and without L-RT by reviewing iCCA patients found to have M1 disease at initial diagnosis at a single institution between 2010 and 2021 who received L-RT.

Conditions

Advanced Intrahepatic Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• Safety and Adverse Events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (2)

Experimental Arm - Liver-RT + Durvalumab

EXPERIMENTAL

Participants will receive treatment in sequence with standard of care systemic therapy

Drug: Durvalumab

Standard of Care Arm - Durvalumab + Gemcitabine + Cisplatin

EXPERIMENTAL

Participants will receive treatment in sequence with standard of care systemic therapy

Drug: Durvalumab; Drug: Gemcitabine; Drug: Cisplatin

Interventions

Cisplatin DRUG

Given by IV

Standard of Care Arm - Durvalumab + Gemcitabine + Cisplatin

Durvalumab DRUG

Given by IV

Experimental Arm - Liver-RT + Durvalumab; Standard of Care Arm - Durvalumab + Gemcitabine + Cisplatin

Gemcitabine DRUG

Given by IV

Standard of Care Arm - Durvalumab + Gemcitabine + Cisplatin

Eligibility Criteria

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

You may qualify if:

• Patients older than the age of 18 years old at the time of study entry.
• Patients with a body mass greater than 30 kg.
• Patients with a pathological diagnosis of intrahepatic cholangiocarcinoma and at least one intrahepatic tumor measuring 3 cm in greatest dimension
• Patients must have pathological or radiographic evidence of either:
• c. locally advanced unresectable iCCA - a multidisciplinary discussion should be documented for patients who have liver confined disease, confirming that the patient is not resectable.
• d. extrahepatic metastasis at the time of enrollment - allowable extrahepatic metastases may include disease in non-regional lymph nodes (note that metastatic involvement of regional lymph nodes in the hilum of the liver alone do not qualify as M1 disease), lung, and/or bone.
• Patients should receive at least 4 cycles of systemic therapy with gemcitabine/cisplatin with durvalumab. If one of the drugs (gemcitabine/cisplatin/durvalumab) was held at any point for medical reasons during the initial 4 cycles, the patient is still eligible as long as the treating team agrees about the ability of the patient to continue systemic therapy.
• Patients must be appropriate candidates for radiation therapy with adequate liver function, at the discretion of the treating physician.

You may not qualify if:

• Adequate normal organ and marrow function as defined below:
• Hemoglobin ≥9.0 g/dL Absolute neutrophil count (ANC) ≥1.0 × 109 /L Platelet count ≥75 × 109/L Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients 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.
• AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN
• Measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
• Males:
• Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)
• Females:
• Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)
• Must have a life expectancy of at least 12 weeks
• At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion (TL) at baseline. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to randomization
• 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 (eg, Health Insurance Portability and Accountability Act in the US, European Union \[EU\] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Participation in another clinical study with an investigational product during the last 1 month.
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• AstraZeneca: collaborator
• Varian Medical Systems, Inc.: collaborator

Study Sites (1)

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Interventions

durvalumab; Gemcitabine; Cisplatin

Intervention Hierarchy (Ancestors)

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

Study Officials

• Eugene Koay, MD,PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eugene Koay, MD,PHD

CONTACT

(713) 563-2381; ekoay@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2025
• First Posted: March 5, 2025
• Study Start: June 10, 2025
• Primary Completion (Estimated): November 19, 2028
• Study Completion (Estimated): November 19, 2030
• Last Updated: March 11, 2026

Record last verified: 2026-03

Locations

US (1)