Testing the Combination of the Anticancer Drug Durvalumab With Chemotherapy (Gemcitabine and Cisplatin) at Improving Outcomes for High-Risk Resectable Liver Cancer Before Surgery
Start Date
7/10/2024
Completion Date
2/12/2027
Summary
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.
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.
Eligibility Criteria
Age Range: 18 years to No maximum
Interventions
Biopsy Procedure
Biospecimen Collection
Cisplatin
Computed Tomography
Durvalumab
Gemcitabine
Magnetic Resonance Imaging
Resection
Conditions
Locations
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California 92612
United States
Los Angeles General Medical Center
Los Angeles, California 90033
United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California 92868
United States
UCHealth University of Colorado Hospital
Aurora, Colorado 80045
United States
Smilow Cancer Hospital-Derby Care Center
Derby, Connecticut 06418
United States
Smilow Cancer Hospital Care Center-Fairfield
Fairfield, Connecticut 06824
United States
Smilow Cancer Hospital Care Center at Glastonbury
Glastonbury, Connecticut 06033
United States
Smilow Cancer Hospital Care Center at Greenwich
Greenwich, Connecticut 06830
United States
Smilow Cancer Hospital Care Center - Guilford
Guilford, Connecticut 06437
United States
Smilow Cancer Hospital Care Center at Saint Francis
Hartford, Connecticut 06105
United States
Yale University
New Haven, Connecticut 06520
United States
Yale-New Haven Hospital North Haven Medical Center
North Haven, Connecticut 06473
United States
Smilow Cancer Hospital Care Center at Long Ridge
Stamford, Connecticut 06902
United States
Smilow Cancer Hospital-Torrington Care Center
Torrington, Connecticut 06790
United States
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut 06611
United States
Smilow Cancer Hospital-Waterbury Care Center
Waterbury, Connecticut 06708
United States
Smilow Cancer Hospital Care Center - Waterford
Waterford, Connecticut 06385
United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida 32610
United States
Emory University Hospital Midtown
Atlanta, Georgia 30308
United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia 30322
United States
Emory Saint Joseph's Hospital
Atlanta, Georgia 30342
United States
Northwestern University
Chicago, Illinois 60611
United States
Memorial Hospital East
Shiloh, Illinois 62269
United States
University of Kansas Clinical Research Center
Fairway, Kansas 66205
United States
University of Kansas Cancer Center
Kansas City, Kansas 66160
United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas 66210
United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas 66205
United States
Ochsner Medical Center Jefferson
New Orleans, Louisiana 70121
United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland 21201
United States
Boston Medical Center
Boston, Massachusetts 02118
United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri 63376
United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri 63141
United States
University of Kansas Cancer Center - Briarcliff
Kansas City, Missouri 64116
United States
University of Kansas Cancer Center - North
Kansas City, Missouri 64154
United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri 64064
United States
Washington University School of Medicine
St Louis, Missouri 63110
United States
Siteman Cancer Center-South County
St Louis, Missouri 63129
United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri 63136
United States
NYP/Weill Cornell Medical Center
New York, New York 10065
United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina 27157
United States
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio 45219
United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio 43210
United States
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio 45069
United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania 15232
United States
Smilow Cancer Hospital Care Center - Westerly
Westerly, Rhode Island 02891
United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee 37232
United States
UT MD Anderson - The Woodlands
Conroe, Texas 77384
United States
UT MD Anderson Cancer Center
Houston, Texas 77030
United States
UT MD Anderson - West Houston
Houston, Texas 77079
United States
UT MD Anderson - League City
League City, Texas 77573
United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas 78229
United States
UT MD Anderson - Sugar Land
Sugar Land, Texas 77478
United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah 84112
United States
University of Virginia Cancer Center
Charlottesville, Virginia 22908
United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia 23298
United States
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin 53718
United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin 53792
United States