Clinical Trials /

Hypofractionated Radiation Therapy and Bintrafusp Alfa for the Treatment of Advanced Intrahepatic Cholangiocarcinoma

NCT04708067

Description:

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.

Related Conditions:
  • Intrahepatic Cholangiocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Hypofractionated Radiation Therapy and Bintrafusp Alfa for the Treatment of Advanced Intrahepatic Cholangiocarcinoma
  • Official Title: "Window of Opportunity" Phase I Trial of Focal Radiotherapy and Bintrafusp Alfa In Patients With Advanced Intrahepatic Cholangiocarcinoma

Clinical Trial IDs

  • ORG STUDY ID: 2020-0899
  • SECONDARY ID: NCI-2020-13928
  • SECONDARY ID: 2020-0899
  • NCT ID: NCT04708067

Conditions

  • Locally Advanced Intrahepatic Cholangiocarcinoma
  • Metastatic Intrahepatic Cholangiocarcinoma
  • Stage III Intrahepatic Cholangiocarcinoma AJCC v8
  • Stage IIIA Intrahepatic Cholangiocarcinoma AJCC v8
  • Stage IIIB Intrahepatic Cholangiocarcinoma AJCC v8
  • Stage IV Intrahepatic Cholangiocarcinoma AJCC v8

Interventions

DrugSynonymsArms
Bintrafusp AlfaAnti-PDL1/TGFb Trap MSB0011359C, M7824, MSB0011359CTreatment (hypofractionated radiation, bintrafusp alfa)

Purpose

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.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (hypofractionated radiation, bintrafusp alfa)ExperimentalPatients undergo hypofractionated radiation therapy 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 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.
  • Bintrafusp Alfa

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must be male or female >= 18 years of age

          -  Patients with histologically or cytologically confirmed intrahepatic
             cholangiocarcinoma. There must be at least two measurable tumors. One larger mass that
             will be radiated and a secondary metastatic site that is amenable to biopsies

          -  Patients must have received at least one standard first-line chemotherapy regimen or
             have refused chemotherapy

          -  Patients with measurable disease assessed at baseline by computed tomography (CT) (or
             magnetic resonance imaging [MRI] where CT is contraindicated) will be entered in this
             study

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Karnofsky > 70)

          -  Leukocytes >= 3,000 cells/mm^3

          -  Absolute neutrophil count >= 1,500 cells/mm^3

          -  Platelets >= 100,000 cells/mm^3

          -  Hemoglobin >= 9 g/dl (no blood transfusions within 4 weeks prior to enrollment)

          -  Total bilirubin < 1.5 x institutional upper limit of normal (IULN)

          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 x IULN without liver metastasis, =< 5 x IULN for patients with liver metastasis

          -  Creatinine within normal institutional limits OR creatinine clearance >= 60
             mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

          -  Women of childbearing potential (defined as not post-menopausal for 65 days or no
             previous surgical sterilization) and fertile men must agree to use adequate
             contraception for the duration of study participation

          -  All female patients of childbearing potential (defined as not post-menopausal for 65
             days or no previous surgical sterilization) must agree to use adequate birth control
             during study treatment and for 90 days after the last dose of study drug and have a
             negative serum pregnancy test at screening

          -  Fertile males must be willing to employ adequate means of contraception during study
             treatment and for 3 months after the last dose of study drug

          -  Male subjects must agree to refrain from sperm donation during the study and for 125
             days after the last dose of study drugs

          -  Ability to read and/or understand the details of the study and provide written
             evidence of informed consent as approved by Institutional Review Board (IRB)/
             Scientific Review Committee (SRC)

        Exclusion Criteria:

          -  Patients who are pregnant or lactating

          -  Patients with uncontrolled intercurrent illness including symptomatic congestive heart
             failure, unstable angina pectoris, cardiac arrhythmia and myocardial infarction (MI)
             within 3 months of initiation of therapy

          -  Patients with recent bacterial, viral, or fungal infection(s) requiring systemic
             antibiotic therapy within one month of enrolling

          -  Patient has undergone major surgery within 4 weeks prior to day 1 of treatment in this
             study. Diagnostic or minimally invasive surgery (i.e., done to obtain a biopsy for
             diagnosis without removal of an organ or to place an abdominal spacer) are acceptable
             at physician discretion

          -  Patient received radiotherapy, surgery, chemotherapy, or an investigational therapy
             within 2 weeks prior to study entry weeks

          -  Patient has serious medical risk factors involving any of the major organ systems such
             that the investigator considers it unsafe for the patient to receive an experimental
             research drug

          -  Serious psychiatric or medical conditions that could interfere with treatment

          -  Major bleeding in the last 4 weeks

          -  Receipt of prior immune checkpoint inhibitors (e.g., anti-CTLA-4, anti-programmed cell
             death receptor 1, anti-programmed cell death ligand 1 [anti-PD-L1], and any other
             antibody or drug specifically targeting T-cell costimulation)

          -  Receiving an immunologically based treatment for any reason, including chronic use of
             systemic steroid at doses >= 7.5 mg/day prednisone equivalent within 14 days prior to
             the first dose of study treatment. Use of inhaled or topical steroids or systemic
             corticosteroids < 7.5 mg is permitted

          -  Receipt of any anticancer medication in the 21 days prior to receiving the first dose
             of study medication or any unresolved toxicity (> grade 1) from previous anticancer
             therapy, except for stable chronic toxicities not expected to resolve, such as
             peripheral neurotoxicity. Prior treatment with nitrosoureas (e.g., carmustine or
             lomustine) require a 6-week washout prior to the first dose of study treatment

          -  Untreated central nervous system (CNS) metastases, or CNS metastases that have
             progressed (e.g., evidence of new or enlarging CNS metastasis or new neurological
             symptoms attributable to CNS metastases). Subjects with treated and clinically stable
             CNS metastases and off all corticosteroids for at least 2 weeks are eligible

          -  Any active or inactive autoimmune process (e.g. rheumatoid arthritis, moderate or
             severe psoriasis, multiple sclerosis, inflammatory bowel disease) or who are receiving
             systemic therapy for an autoimmune or inflammatory disease

               -  Note: Exceptions include subjects with vitiligo, hypothyroidism stable on hormone
                  replacement, controlled asthma, type I diabetes, Graves' disease, or Hashimoto's
                  disease, or with medical monitor approval
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events (AEs)
Time Frame:Up to 60 days
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Objective response rate
Time Frame:Up to 2 years post-treatment
Safety Issue:
Description:Will estimate the objective response rate by Response Evaluation Criteria in Solid Tumors 1.1 criteria separately with appropriate 95% confidence intervals.
Measure:Local progression free survival (LPFS)
Time Frame:Up to 12 months post-treatment
Safety Issue:
Description: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.
Measure:Progression free survival (PFS)
Time Frame:Up to 12 months post-treatment
Safety Issue:
Description: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.
Measure:Overall survival (OS)
Time Frame:Up to 12 months post-treatment
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

January 13, 2021