This phase I trial is to find out the best dose, possible benefits, and/or side effects of hypofractionated radiation therapy and bintrafusp alfa in treating patients with bile duct cancer that has spread to other places in the body (advanced intrahepatic cholangiocarcinoma). Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Immunotherapy with bintrafusp alfa, a bifunctional fusion protein composed of the monoclonal antibody avelumab and TGF-beta, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The combination of hypofractionated radiation therapy and bintrafusp alfa may help to control intrahepatic cholangiocarcinoma.
PRIMARY OBJECTIVE: I. To examine the safety of bintrafusp alfa in combination with hypofractionated radiation therapy for patients with advanced intrahepatic cholangiocarcinoma and recommend a phase II radiation dose. SECONDARY OBJECTIVES: I. To estimate objective response rate, local progression free survival, progression free survival, overall survival with the study regimen. II. To correlate expression of TGF-beta related pathways with clinical outcomes. III. To examine intratumoral pharmacodynamic changes in the immune microenvironment using paired biopsies before and after therapy with the study agents. EXPLORATORY OBJECTIVE: I. To correlate immune biomarkers from pre- and post-treatment tissue, blood, and stool with clinical study endpoints. OUTLINE: This is a dose de-escalation study of radiation therapy followed by a dose-expansion study. Patients undergo hypofractionated radiation therapy once daily (QD) on weekdays (Monday-Friday) for 15 fractions in the absence of disease progression or unacceptable toxicity. Beginning 1 week after completion of radiation therapy, patients receive bintrafusp alfa intravenously (IV) over 1 hour on day 1. Cycles repeat every 14 days for up to 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 12 weeks for up to 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
2
Given IV
Undergo biopsy
Undergo hypofractionated radiation therapy
M D Anderson Cancer Center
Houston, Texas, United States
Incidence of adverse events (AEs)
AEs will be graded according to Common Terminology Criteria for Adverse Events version 5.0. AEs will be summarized by patient incidence rates, therefore, in any tabulation, a patient contributes only once to the count for a given AE preferred term. The number and percentage of patients with any treatment-emergent AE will be summarized for all study patients combined.
Time frame: Up to 60 days
Objective response rate
Will estimate the objective response rate by Response Evaluation Criteria in Solid Tumors 1.1 criteria separately with appropriate 95% confidence intervals.
Time frame: Up to 2 years post-treatment
Local progression free survival (LPFS)
Will estimate the LPFS distributions using the Kaplan-Meier product limit method and report summary measures such as the median value and probabilities at selected times with appropriate 95% confidence intervals.
Time frame: Up to 12 months post-treatment
Progression free survival (PFS)
Will estimate the PFS distributions using the Kaplan-Meier product limit method and report summary measures such as the median value and probabilities at selected times with appropriate 95% confidence intervals.
Time frame: Up to 12 months post-treatment
Overall survival (OS)
Will estimate the OS distributions using the Kaplan-Meier product limit method and report summary measures such as the median value and probabilities at selected times with appropriate 95% confidence intervals.
Time frame: Up to 12 months post-treatment
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