Testing the Combination of the Anticancer Drug Durvalumab With Chemotherapy (Gemcitabine and Cisplatin) at Improving Outcomes for High-Risk Resectable Liver Cancer Before Surgery

September 3, 2026 updated by: National Cancer Institute (NCI)

A Phase II Trial of Durvalumab With Gemcitabine and Cisplatin as Neoadjuvant Therapy for High-Risk Resectable Intrahepatic Cholangiocarcinoma

This phase II trial tests how well giving durvalumab with standard chemotherapy, gemcitabine and cisplatin, before surgery works in treating patients with high risk liver cancer (cholangiocarcinoma) that can be removed by surgery (resectable). Durvalumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving durvalumab with gemcitabine and cisplatin before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed in patients with high risk resectable cholangiocarcinoma.

Study Overview

Status

Suspended

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To examine the proportion of patients who complete neoadjuvant therapy followed by curative intent surgical resection.

SECONDARY OBJECTIVES:

I. To determine the major pathologic response (MPR) rate. (Efficacy) II. To determine the proportion of patients who attain an R0 resection following neoadjuvant therapy. (Efficacy) III. To determine the radiological response rate after 2 and 4 cycles of neoadjuvant therapy. (Efficacy) IV. To determine the overall survival of patients receiving neoadjuvant therapy prior to curative intent surgical resection. (Efficacy) V. To determine the relapse free survival (RFS) of patients receiving neoadjuvant therapy prior to curative intent surgical resection. (Efficacy) VI. To estimate the incidence of adverse events during neoadjuvant therapy which would preclude completion of the neoadjuvant chemotherapy regiment as defined by grade 4 or above adverse events by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. (Feasibility) VII. To determine the proportion of patients who are able to start adjuvant therapy within 10 weeks of surgical resection. (Feasibility) VIII. To determine the proportion of patients who can complete 4 cycles of adjuvant therapy. (Feasibility) IX. To determine the efficacy of therapy in different molecular subtypes (by deoxyribonucleic acid [DNA] profiling, ribonucleic acid [RNA] profiling, and circulating tumor [ct]DNA-based minimal residual disease [MRD]). (Toxicity Profiles and Biomarkers) X. To compare pre- and post-neoadjuvant therapy changes in the phenotypic profiles of circulating immune cells. (Toxicity Profiles and Biomarkers) XI. To correlate ctDNA-based MRD, tissue and blood based immune biomarkers, and body composition with the primary/secondary endpoints. (Toxicity Profiles and Biomarkers)

EXPLORATORY OBJECTIVES:

I. Quantitative European Association for the Study of the Liver (qEASL)-based 3 dimensional (3D) enhancement measurement will be used as a surrogate marker of pathological response.

II. The primary and secondary outcomes will be associated with the visceral abdominal fat, subcutaneous abdominal fat, and muscle at the level of L2/L3.

OUTLINE:

Patients receive durvalumab intravenously (IV) over 60 minutes on day 1 with gemcitabine IV over 30 minutes and cisplatin IV over 60 minutes on days 1 and 8 for 4 cycles and then undergo surgical resection on study. Following surgery, patients may continue the durvalumab, gemcitabine and cisplatin regimen for up to 4 additional cycles. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo computed tomography (CT) scans and/or magnetic resonance imaging (MRI) scans and blood sample collection throughout study, as well as tissue biopsies during screening and on study.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 5 years and then yearly.

Study Type

Interventional

Enrollment (Estimated)

27

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Irvine, California, United States, 92612
        • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
      • Los Angeles, California, United States, 90033
        • Los Angeles General Medical Center
      • Orange, California, United States, 92868
        • UC Irvine Health/Chao Family Comprehensive Cancer Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • UCHealth University of Colorado Hospital
    • Connecticut
      • Derby, Connecticut, United States, 06418
        • Smilow Cancer Hospital-Derby Care Center
      • Fairfield, Connecticut, United States, 06824
        • Smilow Cancer Hospital Care Center-Fairfield
      • Glastonbury, Connecticut, United States, 06033
        • Smilow Cancer Hospital Care Center at Glastonbury
      • Greenwich, Connecticut, United States, 06830
        • Smilow Cancer Hospital Care Center at Greenwich
      • Guilford, Connecticut, United States, 06437
        • Smilow Cancer Hospital Care Center - Guilford
      • Hartford, Connecticut, United States, 06105
        • Smilow Cancer Hospital Care Center at Saint Francis
      • New Haven, Connecticut, United States, 06520
        • Yale University
      • North Haven, Connecticut, United States, 06473
        • Yale-New Haven Hospital North Haven Medical Center
      • Stamford, Connecticut, United States, 06902
        • Smilow Cancer Hospital Care Center at Long Ridge
      • Torrington, Connecticut, United States, 06790
        • Smilow Cancer Hospital-Torrington Care Center
      • Trumbull, Connecticut, United States, 06611
        • Smilow Cancer Hospital Care Center-Trumbull
      • Waterbury, Connecticut, United States, 06708
        • Smilow Cancer Hospital-Waterbury Care Center
      • Waterford, Connecticut, United States, 06385
        • Smilow Cancer Hospital Care Center - Waterford
    • Florida
      • Gainesville, Florida, United States, 32610
        • UF Health Cancer Institute - Gainesville
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • Emory University Hospital Midtown
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital/Winship Cancer Institute
      • Atlanta, Georgia, United States, 30342
        • Emory Saint Joseph's Hospital
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Shiloh, Illinois, United States, 62269
        • Memorial Hospital East
    • Kansas
      • Fairway, Kansas, United States, 66205
        • University of Kansas Clinical Research Center
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Cancer Center
      • Overland Park, Kansas, United States, 66210
        • University of Kansas Cancer Center-Overland Park
      • Westwood, Kansas, United States, 66205
        • University of Kansas Hospital-Westwood Cancer Center
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Medical Center Jefferson
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland/Greenebaum Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston Medical Center
    • Missouri
      • City of Saint Peters, Missouri, United States, 63376
        • Siteman Cancer Center at Saint Peters Hospital
      • Creve Coeur, Missouri, United States, 63141
        • Siteman Cancer Center at West County Hospital
      • Kansas City, Missouri, United States, 64154
        • University of Kansas Cancer Center - North
      • Kansas City, Missouri, United States, 64116
        • University of Kansas Cancer Center - Briarcliff
      • Lee's Summit, Missouri, United States, 64064
        • University of Kansas Cancer Center - Lee's Summit
      • St Louis, Missouri, United States, 63110
        • Washington University School of Medicine
      • St Louis, Missouri, United States, 63129
        • Siteman Cancer Center-South County
      • St Louis, Missouri, United States, 63136
        • Siteman Cancer Center at Christian Hospital
    • New York
      • New York, New York, United States, 10065
        • NYP/Weill Cornell Medical Center
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati Cancer Center-UC Medical Center
      • Columbus, Ohio, United States, 43210
        • Ohio State University Comprehensive Cancer Center
      • West Chester, Ohio, United States, 45069
        • University of Cincinnati Cancer Center-West Chester
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC Hillman Cancer Center
    • Rhode Island
      • Westerly, Rhode Island, United States, 02891
        • Smilow Cancer Hospital Care Center - Westerly
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University/Ingram Cancer Center
    • Texas
      • Conroe, Texas, United States, 77384
        • UT MD Anderson - The Woodlands
      • Houston, Texas, United States, 77030
        • UT MD Anderson Cancer Center
      • Houston, Texas, United States, 77079
        • UT MD Anderson - West Houston
      • League City, Texas, United States, 77573
        • UT MD Anderson - League City
      • Sugar Land, Texas, United States, 77478
        • UT MD Anderson - Sugar Land
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute/University of Utah
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Cancer Center
      • Richmond, Virginia, United States, 23298
        • VCU Massey Comprehensive Cancer Center
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Carbone Cancer Center - University Hospital
      • Madison, Wisconsin, United States, 53718
        • University of Wisconsin Carbone Cancer Center - Eastpark Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed intrahepatic cholangiocarcinoma (iCCA) that is resectable by imaging evaluation. Choice of staging modality is left up to the discretion of the treatment team; we favor high-quality CT scan of the chest/abdomen/pelvis with liver or biliary protocol. Eligibility will be confirmed through central imaging review.
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 10 mm (>= 1 cm) with CT scan, MRI, or calipers by clinical exam.
  • Patients must be an acceptable risk surgical candidate at the time of enrollment, as determined by a board-certified surgeon with expertise in hepatobiliary surgery.

  • High-risk iCCA is defined as the presence of any of these factors:

    • Tumor size > 5 cm.
    • Multifocality or satellitosis limited to the same lobe.
    • Vascular invasion.

    • Suspected or confirmed (via biopsy) regional lymph node metastases.

      • Suspected is defined as lymph nodes that are deemed suspicious for metastasis based on large size (criteria vary per anatomical location; 6-10 mm for abdominal and 8-10 mm for pelvic), enhancement pattern, and shape. These may also include lymph nodes that display fludeoxyglucose F 18 (FDG)-avidity on positron emission tomography (PET) scan, if obtained, in the course of disease work-up (not mandatory).
    • CA 19-9 > 200 U/mL.
  • Patients are treatment naïve for iCCA.
  • Age >= 18 years. Because no dosing or adverse event data are currently available on the use of durvalumab (MEDI4736) in combination with cisplatin and gemcitabine in patients < 18 years of age, children are excluded from this study.
  • Body weight > 30 kg.
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%).
  • Leukocytes >= 3,000/mcL.
  • Hemoglobin >= 9.0 g/dL.
  • Absolute neutrophil count >= 1,500/mcL.
  • Platelets >= 100,000/mcL.
  • Neuropathy grade =< 1 by CTCAE.
  • Albumin >= 2.8 g/dL.
  • Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN).
  • Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) / alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) =< 3 × institutional ULN.
  • Serum creatinine =< 1.5 x institutional ULN.
  • Measured creatinine clearance > 60 mL/min or glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2 (by the Cockcroft-Gault equation).

  • Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

    • Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
    • Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
  • Life expectancy >= 12 weeks.
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
  • Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. If non-protocol anticancer agents for non-study indications is required concurrently with the protocol therapy, the case should be discussed and approved by the study chair and the sponsor (Cancer Therapy Evaluation Program [CTEP]).
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
  • Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Exclusion Criteria:

  • Potential trial participants should have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment.
  • Major surgical procedure (as defined by the Investigator) within 14 days prior to the first dose of durvalumab. Note: Local surgery of isolated lesions for palliative intent or biliary stents is acceptable.

  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. 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.
    • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of durvalumab. Note: Patients, if enrolled, should not receive live vaccine whilst receiving durvalumab and up to 30 days after the last dose of durvalumab.
  • Patients who are receiving any other investigational agents.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to durvalumab, gemcitabine, cisplatin, or other platinum-containing compounds.
  • Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make this protocol unreasonably hazardous.
  • Pregnant women are excluded from this study because durvalumab (MEDI4736) is an anti-PD-L1 monoclonal antibody agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with durvalumab, breastfeeding should be discontinued if the mother is treated with durvalumab. These potential risks may also apply to other agents used in this study. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after durvalumab administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of durvalumab.

  • Patients with active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion:

    • Patients with vitiligo or alopecia.
    • Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement.
    • Any chronic skin condition that does not require systemic therapy.
    • Patients without active disease in the last 5 years may be included but only after consultation with the study physician.
    • Patients with celiac disease controlled by diet alone.
  • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis [TB] testing in line with local practice), hepatitis B (known positive HBV surface antigen [HBsAg] result), or hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • History of allogenic organ transplantation.
  • Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (durvalumab, gemcitabine, cisplatin)
Patients receive durvalumab IV over 60 minutes on day 1 with gemcitabine IV over 30 minutes and cisplatin IV over 60 minutes on days 1 and 8 for 4 cycles and then undergo surgical resection on study. Following surgery, patients may continue the durvalumab, gemcitabine and cisplatin regimen for up to 4 additional cycles. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scans and/or MRI scans and blood sample collection throughout study, as well as tissue biopsies during screening and on study.
Drug: Cisplatin
Given IV
Other Names:
  • CDDP
  • Cis-diamminedichloridoplatinum
  • Cismaplat
  • Cisplatinum
  • Neoplatin
  • Platinol
  • Abiplatin
  • Blastolem
  • Briplatin
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cisplatina
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin
Drug: Gemcitabine
Given IV
Other Names:
  • dFdCyd
  • dFdC
  • Difluorodeoxycytidine
Biological: Durvalumab
Given IV
Other Names:
  • Imfinzi
  • Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer
  • MEDI-4736
  • MEDI4736
  • MEDI 4736
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
  • Sample Collection
Procedure: Computed Tomography
Undergo CT scan
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
  • Diagnostic CAT Scan
  • Diagnostic CAT Scan Service Type
Procedure: Resection
Undergo surgical resection
Other Names:
  • Surgical Resection
Procedure: Magnetic Resonance Imaging
Undergo MRI scan
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Procedure: Biopsy Procedure
Undergo tissue biopsy
Other Names:
  • Bx
  • BIOPSY_TYPE
  • Biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients who complete 4 cycles of neoadjuvant therapy followed by surgical resection
Time Frame: After surgical resection, up to week 18 after starting neoadjuvant therapy
Descriptive analysis will be used. Summary statistics (such as mean, median, range, proportion, as well as the associated 95% confidence interval [CI]) will be reported. Regression models (such as the logistic regression for binary endpoints and the Cox regression for survival endpoints) will be constructed to assess the association between the primary/secondary endpoints and the prognostic or biomarker variables.
After surgical resection, up to week 18 after starting neoadjuvant therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major pathologic response (MPR) rate
Time Frame: After surgical resection, up to week 18 after starting neoadjuvant therapy
MPR will be calculated based on the patients who can successfully undergo surgical resection. Descriptive analysis will be used. Summary statistics (such as mean, median, range, proportion, as well as the associated 95% CI) will be reported. Regression models (such as the logistic regression for binary endpoints and the Cox regression for survival endpoints) will be constructed to assess the association between the primary/secondary endpoints and the prognostic or biomarker variables.
After surgical resection, up to week 18 after starting neoadjuvant therapy
Proportion of patients who attain an R0 margin status after surgical resection
Time Frame: After surgical resection, up to week 18 after starting neoadjuvant therapy
Descriptive analysis will be used. Summary statistics (such as mean, median, range, proportion, as well as the associated 95% CI) will be reported. Regression models (such as the logistic regression for binary endpoints and the Cox regression for survival endpoints) will be constructed to assess the association between the primary/secondary endpoints and the prognostic or biomarker variables.
After surgical resection, up to week 18 after starting neoadjuvant therapy
Radiological response rate
Time Frame: After 2 and 4 cycles of neoadjuvant therapy (cycle length=21 days)
Defined as the percentage of patients with complete response, partial response, stable disease or progressive disease after neoadjuvant therapy by Response Evaluation Criteria in Solid Tumor (RECIST), modified RECIST and quantitative European Association for the Study of the Liver after completing 4 cycles of neoadjuvant therapy. Descriptive analysis will be used. Summary statistics (such as mean, median, range, proportion, as well as the associated 95% CI) will be reported. Regression models (such as the logistic regression for binary endpoints and the Cox regression for survival endpoints) will be constructed to assess the association between the primary/secondary endpoints and the prognostic or biomarker variables.
After 2 and 4 cycles of neoadjuvant therapy (cycle length=21 days)
Proportion of patients who are able to start adjuvant therapy
Time Frame: Up to 10 weeks after surgical resection
Defined as the proportion of patients with Eastern Cooperative Oncology Group > 2, immunotherapy related adverse event > 3, any CTCAE > grade 3 that prevent from starting adjuvant therapy. Regression models (such as the logistic regression for binary endpoints and the Cox regression for survival endpoints) will be constructed to assess the association between the primary/secondary endpoints and the prognostic or biomarker variables.
Up to 10 weeks after surgical resection
Proportion of patients who complete 4 cycles of adjuvant therapy
Time Frame: Up to week 12 after starting adjuvant therapy
Descriptive analysis will be used. Summary statistics (such as mean, median, range, proportion, as well as the associated 95% CI will be reported. Regression models (such as the logistic regression for binary endpoints and the Cox regression for survival endpoints) will be constructed to assess the association between the primary/secondary endpoints and the prognostic or biomarker variables.
Up to week 12 after starting adjuvant therapy
Overall survival (OS)
Time Frame: From randomization to death, assessed up to 2 years
OS, including treatment-related, and disease-related death will be assessed using immune RECIST. Descriptive analysis will be used. Summary statistics (such as mean, median, range, proportion, as well as the associated 95% CI) will be reported. Kaplan-Meier method will be used to estimate the survival curves. Regression models (such as the logistic regression for binary endpoints and the Cox regression for survival endpoints) will be constructed to assess the association between the primary/secondary endpoints and the prognostic or biomarker variables.
From randomization to death, assessed up to 2 years
Relapse free survival (RFS)
Time Frame: From surgery to recurrence of intrahepatic cholangiocarcinoma (iCCa), assessed up to 2 years
Descriptive analysis will be used. Summary statistics (such as mean, median, range, proportion, as well as the associated 95% confidence interval (CI) will be reported. Descriptive analysis will be used. Summary statistics (such as mean, median, range, proportion, as well as the associated 95% CI) will be reported. Kaplan-Meier method will be used to estimate the survival curves. Regression models (such as the logistic regression for binary endpoints and the Cox regression for survival endpoints) will be constructed to assess the association between the primary/secondary endpoints and the prognostic or biomarker variables.
From surgery to recurrence of intrahepatic cholangiocarcinoma (iCCa), assessed up to 2 years
Incidence of adverse events
Time Frame: Up to recurrence of iCCA
Adverse events will be defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Descriptive analysis will be used. Summary statistics (such as mean, median, range, proportion, as well as the associated 95% CI) will be reported. Regression models (such as the logistic regression for binary endpoints and the Cox regression for survival endpoints) will be constructed to assess the association between the primary/secondary endpoints and the prognostic or biomarker variables.
Up to recurrence of iCCA

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tissue and blood based immune biomarkers
Time Frame: Up to week 12 after starting adjuvant therapy
Descriptive analysis will be used. Summary statistics (such as mean, median, range, proportion, as well as the associated 95% CI) will be reported. Regression models (such as the logistic regression for binary endpoints and the Cox regression for survival endpoints) will be constructed to assess the association between the primary/secondary endpoints and the prognostic or biomarker variables.
Up to week 12 after starting adjuvant therapy
Tumor genomics, transcriptional profile and multiplex immunohistochemistry and multiplex immunofluorescence
Time Frame: Up to week 12 after starting adjuvant therapy
Descriptive analysis will be used. Summary statistics (such as mean, median, range, proportion, as well as the associated 95% CI) will be reported. Regression models (such as the logistic regression for binary endpoints and the Cox regression for survival endpoints) will be constructed to assess the association between the primary/secondary endpoints and the prognostic or biomarker variables.
Up to week 12 after starting adjuvant therapy
Changes in circulating immune phenotypic profiles in the neoadjuvant phase
Time Frame: Up to week 12 after starting adjuvant therapy
Descriptive analysis will be used. Summary statistics (such as mean, median, range, proportion, as well as the associated 95% CI) will be reported. Regression models (such as the logistic regression for binary endpoints and the Cox regression for survival endpoints) will be constructed to assess the association between the primary/secondary endpoints and the prognostic or biomarker variables.
Up to week 12 after starting adjuvant therapy
Circulating tumor deoxyribonucleic acid-based minimal residual disease correlated with pathological response and RFS
Time Frame: Up to week 12 after starting adjuvant therapy
Descriptive analysis will be used. Summary statistics (such as mean, median, range, proportion, as well as the associated 95% CI) will be reported. Regression models (such as the logistic regression for binary endpoints and the Cox regression for survival endpoints) will be constructed to assess the association between the primary/secondary endpoints and the prognostic or biomarker variables.
Up to week 12 after starting adjuvant therapy
Measures of body composition and fatty liver from imaging
Time Frame: Up to week 12 after starting adjuvant therapy
Descriptive analysis will be used. Summary statistics (such as mean, median, range, proportion, as well as the associated 95% CI) will be reported. Regression models (such as the logistic regression for binary endpoints and the Cox regression for survival endpoints) will be constructed to assess the association between the primary/secondary endpoints and the prognostic or biomarker variables. Associate changes in subcutaneous abdominal fat, visceral abdominal fat, and muscle at the level of L3 with overall survival and recurrence free survival. Associate changes in body composition with toxicities that are observed during neoadjuvant therapy. Will calculate odds ratios here. Measure changes in the density of the liver before and after neoadjuvant therapy, and associate these with RECIST and responses radiographically. Will also associate density of the liver with pathological response to neoadjuvant therapy. Will use non-parametric statistical tests to do this (e.g., Wilcoxon).
Up to week 12 after starting adjuvant therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Hop S Tran Cao, University of Texas MD Anderson Cancer Center LAO

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 10, 2024

Primary Completion (Estimated)

February 12, 2027

Study Completion (Estimated)

February 12, 2027

Study Registration Dates

First Submitted

September 21, 2023

First Submitted That Met QC Criteria

September 21, 2023

First Posted (Actual)

September 22, 2023

Study Record Updates

Last Update Posted (Actual)

September 4, 2026

Last Update Submitted That Met QC Criteria

September 3, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2023-07031 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • UM1CA186688 (U.S. NIH Grant/Contract)
  • 10608 (Other Identifier: CTEP)
  • 2024-0230 (University of Texas MD Anderson Cancer Center LAO)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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