Y-90 With Durvalumab/Gem/Cis in Intrahepatic Cholangio

NCT05655949 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 21-541
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This trial is designed to study a combination of interventions (chemotherapy, immunotherapy, and radiation) as a potential new treatment for bile duct cancer that cannot be removed with surgery. The specific names of the interventions that will be used are:

• Y-90 (a type of radiation microsphere bead)
• Durvalumab (a type of immunotherapy)
• Gemcitabine (a type of chemotherapy)
• Cisplatin (a type of chemotherapy)

Conditions

Bile Duct Cancer; Cholangiocarcinoma; Cholangiocarcinoma Non-resectable; Cholangiocarcinoma Metastatic; Metastatic Intrahepatic Cholangiocarcinoma

Keywords

Bile Duct Cancer; Cholangiocarcinoma; Cholangiocarcinoma Non-resectable; Cholangiocarcinoma Metastatic; Metastatic Intrahepatic Cholangiocarcinoma

Outcome Measures

Primary Outcomes (2)

• Median Progression Free Survival (PFS)

  PFS is defined as the time from date of entry into the study until the date of disease progression (according to RECIST v1.1 and assessed by an independent central reviewer) or death, whichever occurs first.

  Enrollment to end of treatment and up to 52 weeks thereafter

• Incidence of Grade 3 or Higher Treatment-Related Toxicity

  All grade 3 or higher adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv5 as reported on case report forms. Incidence is the number of patients experiencing at least one treatment-related grade 3 or higher AE of any type during the time of observation.

  Enrollment to end of treatment and up to 52 weeks thereafter

Secondary Outcomes (3)

• Median Overall Survival (OS)

  Enrollment to end of treatment and up to 52 weeks thereafter

• Objective Response Rate (ORR)

  Enrollment to end of treatment and up to 52 weeks thereafter

• Disease Control Rate (DCR)

  Enrollment to end of treatment and up to 52 weeks thereafter

Study Arms (1)

Gemcitabine + Cisplatin + Durvalumab + Yttrium-90 Selective Internal Radiation Therapy

EXPERIMENTAL

Participants will receive: * Cycle 1: Day 1 of 21 Day cycle: Pre-determined dose(s) of Gemcitabine and Cisplatin (Chemotherapy) plus Durvalumab (immunotherapy). Day 8 of 21 Day cycle: Pre-determined dose(s) of Gemcitabine and Cisplatin (Chemotherapy) Week 2 or 3 of 21 Day Cycle: One time treatment of Y-90 radiation. * Cycles 2-8: Day 1 of 21 Day cycle: Pre-determined dose(s) of Gemcitabine and Cisplatin (Chemotherapy) plus Durvalumab (immunotherapy). Day 8 of 21 Day cycle: Pre-determined dose(s) of Gemcitabine and Cisplatin (Chemotherapy) * Cycles 9+: Day 1 of 21 Day Cycle: Durvalumab (immunotherapy) maintenance

Drug: Gemcitabine; Drug: Cisplatin; Drug: Durvalumab; Radiation: Yttrium-90

Interventions

Gemcitabine DRUG

Intravenous infusion

Also known as: Gemzar

Gemcitabine + Cisplatin + Durvalumab + Yttrium-90 Selective Internal Radiation Therapy

Cisplatin DRUG

Intravenous infusion

Also known as: Platinol, Platinol®-AQ

Gemcitabine + Cisplatin + Durvalumab + Yttrium-90 Selective Internal Radiation Therapy

Durvalumab DRUG

Intravenous infusion

Also known as: Imfinzi

Gemcitabine + Cisplatin + Durvalumab + Yttrium-90 Selective Internal Radiation Therapy

Yttrium-90 RADIATION

Injection of radiation microsphere beads

Gemcitabine + Cisplatin + Durvalumab + Yttrium-90 Selective Internal Radiation Therapy

Eligibility Criteria

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

You may qualify if:

• Ability to comprehend and willingness to sign a written ICF for the study
• Male and female participants at least 18 years of age at the time of signing the ICF
• Histologically or cytologically confirmed locally advanced unresectable or metastatic intrahepatic cholangiocarcinoma; at least one intrahepatic lesion must be present
• Radiographically measurable or evaluable disease by CT or MRI per RECIST v1.1 criteria
• ECOG performance status ≤1
• Body weight \>30 kg
• Must have a life expectancy of at least 12 weeks
• Participants must have adequate marrow function as defined below:
• Hemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC) ≥1.0 × 109 /L
• Platelet count ≥75 × 109/L
• Participants must have adequate renal function as defined below:
• Serum creatinine ≤ 1.5 mg/dL OR
• 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
• Participants must have adequate hepatic function as defined below:

You may not qualify if:

• Surgically resectable disease at enrollment
• Histologically or cytologically confirmed diagnosis of primary hepatocellular carcinoma or mixed adenocarcinoma/hepatocellular carcinoma
• Received prior systemic chemotherapy and/or radiotherapy for intrahepatic cholangiocarcinoma. Prior surgical resection and adjuvant chemotherapy or chemoradiotherapy is allowed if more than 6 months have elapsed since last dose of treatment, and if the tumor is amenable to Y-90 SIRT
• Prior treatment with anti-PD-1, anti-PD-L, including durvalumab antibody, or any other drug treatment specifically targeting T-cell co-stimulation or checkpoint pathways
• Any of the following within 6 months of screening:
• New York Heart Association (NYHA) Class III or IV heart failure
• Myocardial infarction, unstable angina pectoris, or symptomatic coronary artery disease
• Unstable arrhythmia
• Stroke to transient ischemic attack
• Previous malignancies, except for adequately treated non-melanoma skin cancer, in-situ cancer, or any other cancer from which the subject has been disease-free for at least 3 years
• Severe chronic obstructive or other pulmonary disease with chronic baseline hypoxemia due to potential for gemcitabine-induced bronchospasm and/or durvalumab-induced pneumonitis
• Major surgery (other than diagnostic) within 4 weeks of study treatment day 1
• Active, uncontrolled or untreated bacterial, viral, or fungal infection that requires systemic therapy
• Active, untreated HIV, HBV, or HCV
• Subjects who have participated in another investigational drug or device study within 4 weeks prior to study registration.

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• Sirtex Medical: collaborator
• Dana-Farber Cancer Institute: collaborator

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

MeSH Terms

Conditions

Bile Duct Neoplasms; Cholangiocarcinoma

Interventions

Gemcitabine; Cisplatin; durvalumab; Yttrium-90

Condition Hierarchy (Ancestors)

Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

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

Study Officials

• Andrea Bullock, MD, MPH

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrea Bullock, MD, MPH

CONTACT

617-667-2100; abullock@bidmc.harvard.edu

Selma Sinanovic, BS

CONTACT

617-667-2100; ssinanov@bidmc.harvard.edu

Study Design

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

Study Record Dates

• First Submitted: December 9, 2022
• First Posted: December 19, 2022
• Study Start: February 13, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu

Locations

US (1)