Preoperative Durvalumab, Cisplatin, Gemcitabine With or Without Futibatinib Targeted Therapy for the Treatment of Resectable Intrahepatic Cholangiocarcinoma, OPTIC Trial

NCT07639528 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: NU 25I12NCI-2026-03371STU00226069P30CA060553
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests the safety and effectiveness of preoperative immunotherapy with durvalumab and chemotherapy with cisplatin and gemcitabine with or without futibatinib targeted therapy in treating patients with intrahepatic cholangiocarcinoma that can be removed by surgery (resectable). Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid (DNA) and may kill cancer cells. Futibatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving immunotherapy with durvalumab and chemotherapy with cisplatin and gemcitabine and/or targeted therapy with futibatinib before surgery may make the tumor smaller for resection and may help prevent the cancer from coming back. Patients whose molecular profiling test result show a genetic change called FGFR2 fusion, rearrangement, or activating mutation, receive immunotherapy, chemotherapy and targeted therapy while patients without a FGFR2 fusion, rearrangement, or activating mutation just receive immunotherapy and chemotherapy. Giving targeted therapy based on molecular profile test results prior to attempted resection for patients with intrahepatic cholangiocarcinoma that has a risk for either not being able to be removed or for coming back after it has been removed may help improve treatment outcomes in patients with resectable intrahepatic cholangiocarcinoma.

Conditions

Resectable Intrahepatic Cholangiocarcinoma

Outcome Measures

Primary Outcomes (2)

• Completion of all preoperative testing and therapy

  Treatment completion is defined as completion of next generation sequencing testing and all preoperative and operative therapy. Will record the completion of all therapy rate, along with the exact 95% binomial confidence interval.

  Up to 3 years

• Incidence of Treatment-Emergent Adverse Events during all preoperative testing and therapy

  Unacceptable toxicity is defined as any grade 3 or higher toxicities by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 that result in a treatment delay of \> 28 days.

  Up to 3 years

Secondary Outcomes (7)

• Radiological response rate

  Up to 3 years

• Pathologic response rate (PRR)

  At the time of surgery

• Response by measuring circulating tumor deoxyribonucleic acid in the blood samples of patients with resectable intrahepatic cholangiocarcinoma

  Up to 3 years

• R0 resection rate

  Up to 7 days after last dose of study drug

• Progression-free survival (PFS)

  From the time of enrollment to either the day of first documented disease progression or death from any cause, assessed up to 3 years

Study Arms (2)

Arm A (durvalumab, cisplatin, gemcitabine, futibatinib)

EXPERIMENTAL

Patients receive durvalumab IV over 60 minutes on day 1 and cisplatin IV over 60 minutes and gemcitabine IV over 30 minutes on days 1 and 8 of one 21-day cycle in the absence of disease progression or unacceptable toxicity while awaiting for NGS results. Patients receive futibatinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MRI, CT and blood sample collection throughout the trial.

Procedure: Biospecimen Collection; Drug: Cisplatin; Procedure: Computed Tomography; Biological: Durvalumab; Drug: Futibatinib; Drug: Gemcitabine; Procedure: Magnetic Resonance Imaging

Arm B (durvalumab, cisplatin, gemcitabine)

ACTIVE COMPARATOR

Patients receive durvalumab IV over 60 minutes on day 1 and cisplatin IV over 60 minutes and gemcitabine IV over 30 minutes on days 1 and 8 of one 21-day cycle in the absence of disease progression or unacceptable toxicity while awaiting for NGS results. Patients continue receiving durvalumab IV over 60 minutes on day 1 and cisplatin IV over 60 minutes and gemcitabine IV over 30 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MRI, CT and blood sample collection throughout the trial.

Procedure: Biospecimen Collection; Drug: Cisplatin; Procedure: Computed Tomography; Biological: Durvalumab; Drug: Gemcitabine; Procedure: Magnetic Resonance Imaging

Interventions

Cisplatin DRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Arm A (durvalumab, cisplatin, gemcitabine, futibatinib); Arm B (durvalumab, cisplatin, gemcitabine)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm A (durvalumab, cisplatin, gemcitabine, futibatinib); Arm B (durvalumab, cisplatin, gemcitabine)

Futibatinib DRUG

Given PO

Also known as: Lytgobi, TAS 120, TAS-120, TAS120

Arm A (durvalumab, cisplatin, gemcitabine, futibatinib)

Durvalumab BIOLOGICAL

Given IV

Also known as: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI 4736, MEDI-4736, MEDI4736

Arm A (durvalumab, cisplatin, gemcitabine, futibatinib); Arm B (durvalumab, cisplatin, gemcitabine)

Gemcitabine DRUG

Given IV

Also known as: dFdC, dFdCyd, Difluorodeoxycytidine

Arm A (durvalumab, cisplatin, gemcitabine, futibatinib); Arm B (durvalumab, cisplatin, gemcitabine)

Biospecimen Collection PROCEDURE

Undergo blood and previously collected tissue sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Arm A (durvalumab, cisplatin, gemcitabine, futibatinib); Arm B (durvalumab, cisplatin, gemcitabine)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm A (durvalumab, cisplatin, gemcitabine, futibatinib); Arm B (durvalumab, cisplatin, gemcitabine)

Eligibility Criteria

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

You may qualify if:

• Patients must have a confirmed biopsy proven diagnosis of resectable intrahepatic cholangiocarcinoma (IHCC) confined to the liver, bile duct, and /or regional lymph nodes confirmed by high-quality cross-sectional imaging by CT or MRI of the chest and MRI of the abdomen, and pelvis performed within 42 days (6 weeks) prior to enrollment. (MRI protocol: With and without gadolineum with T1 and T2 weighted sequences)
• Note: Distant extrahepatic disease is not allowed
• Note: When using CTs in addition to MRI, a high resolution triple phase thin-cut, CT with intravenous +/- oral contrast is the preferred imaging technique for assessing radiographic tumor response
• Patients must have measurable disease per RECIST 1.1
• Patients must be treatment naïve
• Patients must be age ≥ 18 years
• Patient with CORE biopsy for diagnosis that is sufficient enough to do NGS
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Absolute neutrophil count (ANC) ≥ 1,000/mcL
• Hemoglobin (Hgb) ≥ 8 g/dL (blood transfusion allowed up to 7 days prior to starting on study drug)
• Serum total bilirubin ≤ 2 X Institutional upper limit of normal (ULN)
• For Gilbert's disease: these value does not apply and treatment will be done per treating physician
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) ≤ 5 x institutional ULN
• For Gilbert's disease: these value does not apply and treatment will be done per treating physician
• Alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase \[SGPT\]) ≤ 5 x institutional ULN

You may not qualify if:

• Patients with peripheral neuropathy of grade 2 or greater by Common Terminology Criteria for Adverse Events (CTCAE) 5.0. In CTCAE version 5.0 grade 2 sensory neuropathy is defined as "moderate symptoms; limiting instrumental activities of daily living (ADLs)
• Patients who are receiving any other investigational agents
• Patients who have current evidence of corneal or retinal disorder/keratopathy including, but not limited to, bullous/band keratopathy, inflammation or ulceration, keratoconjunctivitis, confirmed by ophthalmic examination
• Note: Patients with asymptomatic ophthalmic conditions assessed by the investigator to pose minimal risk for study participation may be enrolled in the study
• Patients who have used medications known to prolong the QT interval and/or are associated with a risk of Torsades de Pointes (TdP) 7 days prior to first dose of study drug
• Patients who have clinically significant cardiac disease including any of the following: Congestive heart failure requiring treatment (New York Heart Association grade ≥ 2), or uncontrolled hypertension (refer to the European Society of Cardiology and European Society of Hypertension guidelines (Williams et al 2018)
• Patients with corrected QT interval using Fridericia formula (QTcF) \> 470 msec (males and females)
• Note: If the QTcF is \> 470 msec in the first electrocardiogram (ECG), a total of 3 ECGs separated by at least 5 minutes should be performed. If the average of these 3 consecutive results for QTcF is ≤ 470 msec, the patient meets eligibility in this regard
• Patient with known history of congenital long QT syndrome
• Patients who have current evidence of concerning endocrine alterations of calcium/phosphate homeostasis, eg, parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis etc., in the opinion of the investigator OR and taking medications which increase serum phosphorus and/or calcium concentration
• Patients who have abnormal calcium or phosphorus, or calcium-phosphorus product ≥ 55 mg\^2 /dL2:
• Inorganic phosphorus above local normal limits
• Total corrected serum calcium above local normal limits
• Patients who are currently receiving or are planning to receive during participation in this study, treatment with agents that are known strong inducers or inhibitors of CYP3A4
• Note: Patients are not permitted to receive enzyme-inducing anti-epileptic drugs

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Interventions

Specimen Handling; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; durvalumab; Immunoglobulin G; Disulfides; futibatinib; Gemcitabine; Magnetic Resonance Spectroscopy

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Shishir K Maithel, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Coordinator

CONTACT

3126951301; cancertrials@northwestern.edu

Study Design

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

Study Record Dates

• First Submitted: June 1, 2026
• First Posted: June 10, 2026
• Study Start (Estimated): December 10, 2027
• Primary Completion (Estimated): December 10, 2030
• Study Completion (Estimated): December 10, 2031
• Last Updated: June 10, 2026

Record last verified: 2026-06

Locations

US (1)