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BN Brachyury and Radiation in Chordoma

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ClinicalTrials.gov Identifier: NCT03595228
Recruitment Status : Completed
First Posted : July 23, 2018
Results First Posted : April 14, 2023
Last Update Posted : April 14, 2023
Sponsor:
Information provided by (Responsible Party):
Bavarian Nordic

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Chordoma Biological: BN-Brachyury plus radiation Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Trial of BN-Brachyury and Radiation Therapy in Patients With Advanced Chordoma
Actual Study Start Date : October 31, 2018
Actual Primary Completion Date : December 10, 2021
Actual Study Completion Date : January 25, 2022

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Chordoma

Arms and Interventions
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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.


Outcome Measures
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Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Within 12 months post-completion of radiation on target lesion(s) based on modified RECIST v1.1 ]
    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%.


Secondary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: 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. ]
    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.

  2. Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Best Observed Scores [ Time Frame: 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. ]
    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.

  3. Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Worst Observed Scores [ Time Frame: 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. ]
    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.


Other Outcome Measures:
  1. Number of Participants With Injection Site Reaction Adverse Events by Preferred Term [ Time Frame: 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. ]
    Includes Adverse Events that have injection site reactions indicated as the Adverse Event High Level Terms

  2. Frequencies of Participants With Occurrence, Severity and Seriousness of Adverse Events [ Time Frame: 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. ]
    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.

  3. Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) [ Time Frame: 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. ]
    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.


Eligibility Criteria
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Ages Eligible for Study:   12 Years to 99 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03595228


Locations
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United States, Arizona
Mayo Clinic, Arizona
Phoenix, Arizona, United States, 85054
United States, Florida
Mayo Clinic, Florida
Jacksonville, Florida, United States, 32224
United States, Massachusetts
Massachusetts General Hospital, Cancer Center
Boston, Massachusetts, United States, 02114
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Bavarian Nordic
Investigators
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Principal Investigator: Gregory Cote, MD Massachusetts General Hospital
  Study Documents (Full-Text)

Documents provided by Bavarian Nordic:
Study Protocol  [PDF] August 22, 2019
Statistical Analysis Plan  [PDF] November 2, 2021

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Bavarian Nordic
ClinicalTrials.gov Identifier: NCT03595228    
Other Study ID Numbers: BRACHY-CHOR-001
First Posted: July 23, 2018    Key Record Dates
Results First Posted: April 14, 2023
Last Update Posted: April 14, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Chordoma
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms