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BN Brachyury and Radiation in Chordoma

Primary Purpose

Chordoma

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

BN-Brachyury plus radiation

About this trial

This is an interventional treatment trial for Chordoma

Eligibility Criteria

12 Years - 99 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Mayo Clinic, Arizona
Mayo Clinic, Florida
Massachusetts General Hospital, Cancer Center
Washington University School of Medicine
MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BN-Brachyury plus radiation

Arm Description

BN-Brachyury as both MVA and FPV are given before radiation, and followed by FPV-Brachyury

Outcomes

Primary Outcome Measures

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%.

Secondary Outcome Measures

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.

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.

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.

Full Information

NCT ID

NCT03595228

First Posted

July 12, 2018

Last Updated

March 22, 2023

Sponsor

Bavarian Nordic

1. Study Identification

Unique Protocol Identification Number

NCT03595228

Brief Title

BN Brachyury and Radiation in Chordoma

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Completed

Study Start Date

October 31, 2018 (Actual)

Primary Completion Date

December 10, 2021 (Actual)

Study Completion Date

January 25, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bavarian Nordic

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chordoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

29 (Actual)

8. Arms, Groups, and Interventions

Arm Title

BN-Brachyury plus radiation

Arm Type

Experimental

Arm Description

BN-Brachyury as both MVA and FPV are given before radiation, and followed by FPV-Brachyury

Intervention Type

Biological

Intervention Name(s)

BN-Brachyury plus radiation

Intervention Description

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.

Primary Outcome Measure Information:

Title

Objective Response Rate (ORR)

Description

Time Frame

Within 12 months post-completion of radiation on target lesion(s) based on modified RECIST v1.1

Secondary Outcome Measure Information:

Title

Progression-free Survival (PFS)

Description

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.

Title

Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Best Observed Scores

Description

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.

Title

Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Worst Observed Scores

Description

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.

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.

Other Pre-specified Outcome Measures:

Title

Number of Participants With Injection Site Reaction Adverse Events by Preferred Term

Description

Includes Adverse Events that have injection site reactions indicated as the Adverse Event High Level Terms

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.

Title

Frequencies of Participants With Occurrence, Severity and Seriousness of Adverse Events

Description

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.

Time Frame

Title

Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry)

Description

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.

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.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Maximum Age & Unit of Time

99 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gregory Cote, MD

Organizational Affiliation

Massachusetts General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic, Arizona

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85054

Country

United States

Facility Name

Mayo Clinic, Florida

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32224

Country

United States

Facility Name

Massachusetts General Hospital, Cancer Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Washington University School of Medicine

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

MD Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34266694

Citation

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.

Results Reference

derived

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BN Brachyury and Radiation in Chordoma

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