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Locally Advanced Intrahepatic CholangiocarcinomaPhase 1NCT04708067

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

A Phase 1 study testing Bintrafusp Alfa, Biopsy and Hypofractionated Radiation Therapy in people with Locally Advanced Intrahepatic Cholangiocarcinoma and Metastatic Intrahepatic Cholangiocarcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Bintrafusp Alfa, Biopsy and Hypofractionated Radiation Therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteUnited States
Study dates
31 Aug 2021to 2 Feb 2027
Phase
Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: "Window of Opportunity" Phase I Trial of Focal Radiotherapy and Bintrafusp Alfa In Patients With Advanced Intrahepatic Cholangiocarcinoma

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

  1. 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.

Being tested
Bintrafusp Alfa, Biopsy, Hypofractionated Radiation Therapy
Medical subject headings
Cholangiocarcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bintrafusp AlfaDrug

    Also called Anti-PDL1/TGFb Trap MSB0011359C, M7824, MSB0011359C

    Given IV

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo biopsy

  • Hypofractionated Radiation TherapyRadiation

    Also called Hypofractionated Radiotherapy, hypofractionation

    Undergo hypofractionated radiation therapy

Study groups in NCT04708067
Study groupRoleWhat they receive
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.
Receives: Drug: Bintrafusp Alfa; Procedure: Biopsy; Radiation: Hypofractionated Radiation Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 60 days

Secondary outcomes (4)

  1. 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.

    Measured: Up to 2 years post-treatment

  2. 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.

    Measured: Up to 12 months post-treatment

  3. 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.

    Measured: Up to 12 months post-treatment

  4. 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.

    Measured: Up to 12 months post-treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jan 2021
  2. Study start31 Aug 2021
  3. Primary completion2 Feb 2027 (estimated)
  4. Study completion2 Feb 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04708067
Sponsor's protocol ID
2020-0899
Other IDs
NCI-2020-13928, 2020-0899
Status last verified
Sep 2026
First submitted
12 Jan 2021
Last updated
14 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

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