BN Brachyury and Radiation in Chordoma

A Phase 2 Trial of BN-Brachyury and Radiation Therapy in Patients With Advanced Chordoma

The goal of this study is to determine if the combination of BN-Brachyury plus radiation therapy can induce objective radiographic response rate (ORR) in patients, using a Simon 2-stage optimal design. In stage 1, a minimum of threshold of activity is needed to proceed to stage 2.

Study Overview

• Status: Completed
• Conditions: Chordoma
• Intervention / Treatment: Biological: BN-Brachyury plus radiation

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic, Arizona
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic, Florida
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital, Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 99 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have histologically confirmed chordoma
• Patients must have measurable disease by RECIST 1.1
• Patients must be scheduled to have radiation therapy to at least 1 target lesion.
• Age ≥12 years
• Patients must have normal organ and marrow function
• Must have recovered completely from any reversible toxicity associated with recent therapy.
• There should be a minimum of 2 weeks from any chemotherapy, small molecule/targeted therapy, immunotherapy and/or radiation prior to enrolment
• Females of childbearing potential and male partners of Females of childbearing potential must agree to use effective birth control or abstinence from screening to after the last vaccination therapy

Exclusion Criteria:

• Concurrent treatment for cancer, with specific exceptions noted in the inclusion criteria
• Chronic hepatitis B or C infection.
• Any significant disease, that in the opinion of the investigator may impair the patient's tolerance of trial treatment.
• Significant dementia, altered mental status, or any psychiatric condition that would prohibit the understanding, or rendering of informed consent.
• Active autoimmune diseases requiring treatment or a history of autoimmune disease that might be stimulated by vaccine treatment. This requirement is due to the potential risks of exacerbating autoimmunity.
• Concurrent use of systemic steroids, except for physiological doses of systemic steroid replacement or local steroid use.
• Patients who are receiving any other investigational agents within 28 days before start of trial treatment.
• History of allergic reactions attributed to compounds of similar chemical or biological composition to MVA-BN/FPV-Brachyury or other agents used in trial. History of allergic reactions to aminoglycoside antibiotic or egg products.
• Serious or uncontrolled intercurrent illness, included but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with trial requirements.
• Pregnant women are excluded from this trial due to the unknown effects of the BN-Brachyury on the fetus or infant.
• HIV-positive patients are ineligible because of the potential for decreased immune response to the vaccine.
• Significant cardiovascular disease, which includes but is not limited to New York Heart Association Heart Failure Class II or greater, myocardial infarction within the previous 3 months, unstable arrhythmias, unstable angina.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BN-Brachyury plus radiation; BN-Brachyury as both MVA and FPV are given before radiation, and followed by FPV-Brachyury	Biological: BN-Brachyury plus radiation; MVA-BN-Brachyury injections will be given on day 0 and 14. FPV-Brachyury injection will be given on day 28, followed by radiation on days 42 through approximately day 70. FPV-Brachyury will then be given two weeks after radiation then every 6-12 weeks through 110 weeks after radiation is complete.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Rate of subjects achieving a best response of either Complete Response or Partial Response per modified RECIST v1.1. A modified RECIST v1.1 assessment is based on targeted radiated lesion(s). Progression of a non-target lesion does not result in disease progression by the modified RECIST evaluation for this trial. Assessment for targeted radiated lesion(s): Complete Response (CR)=Disappearance of all target radiated lesions; Partial Response (PR)= >=30% decrease in the sum of the longest diameter of target radiated lesions; Progressive Disease (PD) = >=20% increase in the sum of the longest diameter of target radiated lesions, Stable Disease (SD)=-30%<sum of the longest diameter of target radiated lesions<20%.	Within 12 months post-completion of radiation on target lesion(s) based on modified RECIST v1.1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	Kaplan-Meier of the time interval from first treatment to objective tumor progression based on modified RECIST v1.1 or death. A modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) based on targeted radiated lesion(s) will be used. Progression will be defined as a 20% increase in the sum of the longest diameter of target radiated lesions in this trial, and a progression of a non-target lesion does not result in disease progression by the modified RECIST evaluation used for this trial.	Time from the day of first treatment to the start of disease progression or death, whichever occurs first up to 30 days after last tumor assessment visit. Data were collected up to 29 months.
Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Best Observed Scores	Pain intensity and pain interference scores are summarized. Pain intensity scores includes pain items "Worst Pain in the Last Week", "Least Pain in the Last Week", and "Average Pain in the Last Week" and "Pain Right Now". Composite pain severity score (a mean severity score of the four pain items listed before). Composite pain interference score (a mean of the seven interference items). This will be calculated if at least four of the seven interference items have been completed on a given administration. Pain scores range from 0 to 10 with a score of 10 is the worst pain imaginable and a score of 0 is no pain. Best observed scores is the lowest score value observed.	Overall Treatment Period: The time from the day of first treatment to the last scheduled trial visit, approximately 30 days after the last treatment visit. Data were collected up to 29 months.
Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Worst Observed Scores	Pain intensity and pain interference scores are summarized. Pain intensity scores includes pain items "Worst Pain in the Last Week", "Least Pain in the Last Week", and "Average Pain in the Last Week" and "Pain Right Now". Composite pain severity score (a mean severity score of the four pain items listed before). Composite pain interference score (a mean of the seven interference items). This will be calculated if at least four of the seven interference items have been completed on a given administration. Pain scores range from 0 to 10 with a score of 10 is the worst pain imaginable and a score of 0 is no pain. Worst observed scores is the highest score value observed.	Overall Treatment Period: The time from the day of first treatment to the last scheduled trial visit, approximately 30 days after the last treatment visit. Data were collected up to 29 months.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Injection Site Reaction Adverse Events by Preferred Term	Includes Adverse Events that have injection site reactions indicated as the Adverse Event High Level Terms	All AEs that are presented during or following initiation of trial treatment or worsens in severity are collected through the last scheduled visit (approximately 30 days after the last dose of treatment). Data were collected up to 29 months.
Frequencies of Participants With Occurrence, Severity and Seriousness of Adverse Events	Occurrence is defined as the number of participants who experienced an AE. Related SAEs are defined as those for which causality to trial vaccine was considered possible, probable, definite, or was missing. Intensity is defined per CTCAE v4.03 grade.	All AEs that are presented during or following initiation of trial treatment or worsens in severity are collected through the last scheduled visit (approximately 30 days after the last dose of treatment). Data were collected up to 29 months.
Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry)	For hematology and chemistry laboratory parameters with CTCAE grading scales, toxicity grade shift is defined to evaluated categorical changes from baseline results to post-treatment results with respect to dichotomized CTCAE grading value (<= Grade 2, >= Grade 3). Grade 0=No adverse event or within normal limits; Grade 1=Mild adverse event; Grade 2=Moderate adverse event; Grade 3=Severe and undesirable adverse event; Grade 4=Life-threatening or disabling adverse event; Grade 5=Death related to adverse event. Higher scores mean worse outcome.	Overall Treatment Period: The time from the day of first treatment to the last scheduled trial visit, approximately 30 days after the last treatment visit. Data were collected up to 29 months.

Collaborators and Investigators

• Sponsor: Bavarian Nordic
• Investigators: Principal Investigator: Gregory Cote, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Wedekind MF, Widemann BC, Cote G. Chordoma: Current status, problems, and future directions. Curr Probl Cancer. 2021 Aug;45(4):100771. doi: 10.1016/j.currproblcancer.2021.100771. Epub 2021 Jul 1.

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2018
• Primary Completion (Actual): December 10, 2021
• Study Completion (Actual): January 25, 2022

Study Registration Dates

• First Submitted: July 12, 2018
• First Submitted That Met QC Criteria: July 12, 2018
• First Posted (Actual): July 23, 2018

Study Record Updates

• Last Update Posted (Actual): April 14, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Germ Cell and Embryonal; Chordoma
• Other Study ID Numbers: BRACHY-CHOR-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No