Clinical trial NCT03595228: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chordoma
Lead sponsor: Bavarian Nordic
Sponsor class: INDUSTRY
First posted: 2018-07-23
Enrollment: 29
Sex: ALL
Minimum age (years): 12
Maximum age (years): 99
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Within 12 months post-completion of radiation on target lesion(s) based on modified RECIST v1.1
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: 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.
measure: Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Best Observed Scores
timeFrame: 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.
measure: Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Worst Observed Scores
timeFrame: 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:
measure: Number of Participants With Injection Site Reaction Adverse Events by Preferred Term
timeFrame: 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.
measure: Frequencies of Participants With Occurrence, Severity and Seriousness of Adverse Events
timeFrame: 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.
measure: Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry)
timeFrame: 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.
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic, Arizona
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic, Florida
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital, Cancer Center
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Massachusetts General Hospital
name: Gregory Cote, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.