BN Brachyury and Radiation in Chordoma

NCT03595228 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: BRACHY-CHOR-001
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 5

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.

Conditions

Chordoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Progression-free Survival (PFS)

  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

  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

  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 Outcomes (3)

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

  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

  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)

  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.

Study Arms (1)

BN-Brachyury plus radiation

EXPERIMENTAL

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

Biological: BN-Brachyury plus radiation

Interventions

BN-Brachyury plus radiation BIOLOGICAL

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.

BN-Brachyury plus radiation

Eligibility Criteria

• Age: 12 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bavarian Nordic: lead

Study Sites (5)

Mayo Clinic, Arizona

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic, Florida

Jacksonville, Florida, 32224, United States

Location

Massachusetts General Hospital, Cancer Center

Boston, Massachusetts, 02114, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 34266694 DERIVED

MeSH Terms

Conditions

Chordoma

Interventions

Radiation

Condition Hierarchy (Ancestors)

Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Physical Phenomena

Results Point of Contact

• Title: Bavarian Nordic Call Center
• Organization: Bavarian Nordic A/S

medical.information_us@bavarian-nordic.com

1-844-422

Study Officials

• Gregory Cote, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2018
• First Posted: July 23, 2018
• Study Start: October 31, 2018
• Primary Completion: December 10, 2021
• Study Completion: January 25, 2022
• Last Updated: April 14, 2023
• Results First Posted: April 14, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)