Radioembolization With Tremelimumab and Durvalumab for Locally Advanced Unresectable or Oligo-Metastatic Intrahepatic Cholangiocarcinoma
Phase 1 Trial of Safety and Preliminary Efficacy of Segmental Ablative Radioembolization in Combination With Tremelimumab Plus Durvalumab (MEDI4736) in Patients With Unresectable, or Oligo-Metastatic Cholangiocarcinoma Who Are Not Candidates for Curative Therapy (RAIDEN Trial)
3 other identifiers
interventional
16
1 country
1
Brief Summary
This phase I trial tests the safety and side effects of yttrium-90 (Y90) radioembolization combined with immunotherapy drugs tremelimumab and durvalumab in treating patients with intrahepatic cholangiocarcinoma (cancer of the bile ducts in the liver) that has spread to nearby tissue or lymph nodes (locally advanced) and cannot be removed by surgery (unresectable) who are not candidates for curative therapy or that has spread from where it first started (primary side) to multiple other places in the body (oligo-metastatic). Cholangiocarcinoma is a rare but aggressive cancer with limited curative options outside of surgery. Immunotherapy has shown modest benefit in hepatobiliary (liver, bile ducts, and gallbladder) cancers including cholangiocarcinoma. Radioembolization is a type of radiation therapy used to treat liver cancer that is advanced or has come back where tiny beads that hold the radioactive substance (radioisotope) yttrium Y90 are injected into or near the hepatic artery (the main blood vessel that carries blood to the liver). The beads collect in the tumor and the Y90 gives off radiation. This destroys the blood vessels that the tumor needs to grow and kills the tumor cells. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving Y90 radioembolization in combination with tremelimumab and durvalumab immunotherapy may be safe and beneficial in treating patients with locally advanced, unresectable or oligo-metastatic intrahepatic cholangiocarcinoma who are not candidates for curative therapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Jun 2024
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 6, 2023
CompletedFirst Posted
Study publicly available on registry
September 28, 2023
CompletedStudy Start
First participant enrolled
June 6, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 30, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
November 30, 2028
October 20, 2025
October 1, 2025
2.5 years
September 6, 2023
October 15, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) (Cohort 1)
Dose-limiting toxicities (DLTs) will be defined as an adverse event (AE) attributed as definitely, probably, or possibility related to the study treatment in the first cycle. All the relevant results pertaining to toxicity will be examined in an exploratory and hypothesis-generating fashion. The number and severity of all adverse events will be tabulated and summarized in this patient population. The grade 3+ AEs will also be described and summarized in a similar fashion. Toxicity is defined as AEs that are classified as either possibly, probably, or definitely related to study treatment. Non-hematologic toxicities will be evaluated via the ordinal Common Terminology Criteria (CTC) standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading. Overall toxicity will be explored and summarized.
Day 0 to day 28
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) (Cohort 2)
DLTs will be defined as an AE attributed as definitely, probably, or possibility related to the study treatment in the first cycle. All the relevant results pertaining to toxicity will be examined in an exploratory and hypothesis-generating fashion. The number and severity of all adverse events will be tabulated and summarized in this patient population. The grade 3+ AEs will also be described and summarized in a similar fashion. Toxicity is defined as AEs that are classified as either possibly, probably, or definitely related to study treatment. Non-hematologic toxicities will be evaluated via the ordinal CTC standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading. Overall toxicity will be explored and summarized.
Day 14 to day 42
Secondary Outcomes (13)
Overall efficacy
Up to 24 months
Median progression free survival
Up to 24 months
Median overall survival
Up to 24 months
Objective response rate (complete response and partial response)
From the start of the treatment until disease progression/recurrence, assessed up to 24 months
Duration of response
Up to 24 months
- +8 more secondary outcomes
Study Arms (2)
Cohort I: (Y90, tremelimumab on day 1, cycle 1, durvalumab)
EXPERIMENTALPatients receive transarterial Y90 radioembolization and tremelimumab IV over 1 hour on day 1 of cycle 1 and durvalumab IV over 1 hour on day 1 of each cycle. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo mapping angiography during screening as well as CT and MRI or PET/CT during screening and on study. Patients also undergo blood sample collection throughout the trial and may undergo tumor biopsy during screening and on study.
Cohort II: (Y90, tremelimumab on day 14, cycle 1, durvalumab )
EXPERIMENTALPatients receive transarterial Y90 radioembolization on day 1 of cycle 1 and receive tremelimumab IV over 1 hour on day 14 of cycle 1 and durvalumab IV over 1 hour on day 14 of each cycle. Cycles repeat every 42 days for cycle 1 and then every 28 days for cycles 2-24 in the absence of disease progression or unacceptable toxicity. Patients also undergo mapping angiography during screening, as well as CT and MRI or PET/CT during screening and on study. Patients also undergo blood sample collection throughout the trial and may undergo tumor biopsy during screening and on study.
Interventions
Undergo mapping angiography
Undergo biopsy
Undergo blood sample collection
Undergo CT
Given IV
Undergo MRI
Undergo PET/CT
Given IV
Receive transarterial Y90 radioembolization
Eligibility Criteria
You may qualify if:
- Age \>= 18 years with body weight \> 30 kg
- Histologically or cytologically confirmed, locally advanced intrahepatic cholangiocarcinoma that is not amenable to resection, transplantation, or thermal ablation. Oligometastatic intrahepatic cholangiocarcinoma is also eligible. Specifically, such patients must have EITHER =\< 3 malignant extrahepatic lymph nodes (short axis diameter \>= 3cm) OR metastatic lesions in one organ other than liver (if only single lesion is present diameter MUST be \< 3cm, if up to 3 lesions in one organ each lesion MUST be =\< 1cm)
- Measurable disease
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- Hemoglobin \>= 9.0 g/dL (=\< 14 days prior to registration)
- Absolute neutrophil count (ANC) \>= 1000/mm\^3 (=\< 14 days prior to registration)
- Platelet count \>= 75,000/mm\^3 (=\< 14 days prior to registration)
- Total bilirubin =\< 1.5 x upper limit of normal (ULN) (patients with known Gilbert disease who have serum bilirubin level 3 x ULN may be enrolled) (=\< 14 days prior to registration)
- Alanine aminotransferase (ALT) and aspartate transaminase (AST) =\< 5 x ULN (=\< 14 days prior to registration)
- Calculated creatinine clearance \>= 40 ml/min using the Cockcroft- Gault formula or measured creatinine clearance \> 40 ml/min (=\< 14 days prior to registration)
- International normalized ratio (INR) =\< 1.6. Note: INR prolongation due
- Anticoagulation (INR \>= 2.0 but =\< 3.0)) for prophylaxis in patients without liver cirrhosis could be exception
- Adequate hepatic function Child Pugh A and albumin-bilirubin (ALBI) 1 or 2
- Patients with concurrent hepatitis B (HBV) or hepatitis C virus (HCV) infection should meet the following criteria:
- Patient with HBV or should be monitored for viral levels during study participation
- +5 more criteria
You may not qualify if:
- Concurrent enrollment in another clinical study, unless it is an observational clinical study or during the follow up period of an interventional study
- Surgery =\< 28 days prior to registration
- Chemotherapy =\< 4 weeks prior to registration
- History of \> 1 prior systemic therapy for cholangiocarcinoma not including that in the adjuvant setting. Patients who progressed during or =\< 6 months from completion of adjuvant therapy are excluded
- Patients with grade \>= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician
- Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the study physician
- History of previous locoregional therapy
- Previous use of therapeutic cancer vaccines
- Unstable liver function and/ or a change in Child Pugh score during screening
- Child Pugh B or greater
- ALBI grade \> 2
- Model for End-Stage Liver Disease (MELD) \> 10
- Patient is unable to undergo mapping angiography or mapping angiography demonstrates tumor blood supply that does not lend itself to transarterial therapy
- A lung shunt fraction greater than 30 Gy within a single session, or cumulative does greater than 50Gy
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- +31 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Mayo Cliniclead
Study Sites (1)
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Umair Majeed, MD
Mayo Clinic
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 6, 2023
First Posted
September 28, 2023
Study Start
June 6, 2024
Primary Completion (Estimated)
November 30, 2026
Study Completion (Estimated)
November 30, 2028
Last Updated
October 20, 2025
Record last verified: 2025-10