Chordoma
Conditions
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.
Interventions
BIOLOGICALBN-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.
Sponsors
Bavarian Nordic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 99 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 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
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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 | 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. |
| 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. | 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
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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. |
| 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. | 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. |
| 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. | Includes Adverse Events that have injection site reactions indicated as the Adverse Event High Level Terms |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BN-Brachyury Plus Radiation BN-Brachyury as both MVA and FPV are given before radiation, and followed by FPV-Brachyury
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. | 29 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | Lack of Efficacy | 13 |
| Overall Study | Withdrawal by Sponsor | 1 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | BN-Brachyury Plus Radiation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 15 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| Age, Continuous | 65.9 years STANDARD_DEVIATION 10.82 |
| Current Disease Status Localized | 0 Participants |
| Current Disease Status Locally Advanced | 5 Participants |
| Current Disease Status Metastatic | 24 Participants |
| Disease Status at Diagnosis Localized | 20 Participants |
| Disease Status at Diagnosis Locally Advanced | 7 Participants |
| Disease Status at Diagnosis Metastatic | 2 Participants |
| ECOG Status 0 | 12 Participants |
| ECOG Status 1 | 17 Participants |
| ECOG Status 2 | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Hepatitis B Surface Negative | 29 Participants |
| Hepatitis B Surface Positive | 0 Participants |
| Hepatitis C Virus Negative | 29 Participants |
| Hepatitis C Virus Positive | 0 Participants |
| Historical Classification Chondroid | 0 Participants |
| Historical Classification Classical | 26 Participants |
| Historical Classification Not Reported | 3 Participants |
| HIV Antibody Negative | 29 Participants |
| HIV Antibody Positive | 0 Participants |
| Primary Tumor Site Clival | 3 Participants |
| Primary Tumor Site Mobile Spine | 8 Participants |
| Primary Tumor Site Sacral | 18 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 26 Participants |
| Region of Enrollment United States | 29 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 29 |
| other Total, other adverse events | 29 / 29 |
| serious Total, serious adverse events | 8 / 29 |
Outcome results
Primary
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%.
Time frame: Within 12 months post-completion of radiation on target lesion(s) based on modified RECIST v1.1
Population: Evaluable Analysis Set conisits of subjects who have completed two prime doses of MVA-BN-Brachyury and one booster dose of FPV-Brachyury prior to radiation, have completed radiation therapy, have at least 3 out of 4 booster doses of FPV-Brachyury in 14 weeks after radation, have both baseline and at least one post-baseline computed tomography (CT) or magnetic resonance imaging (MRI) scan for objective tumor evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BN-Brachyury Plus Radiation | Objective Response Rate (ORR) | 7.7 percentage of subjects with OR |
Secondary
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.
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.
Population: Evaluable Analysis Set consists of subjects who have completed two prime doses of MVA-BN-Brachyury and one booster dose of FPV-Brachyury prior to radiation, have completed radiation therapy, have at least 3 out of 4 booster doses of FPV-Brachyury in 14 weeks after radiation, have both baseline and at least one post-baseline computed tomography (CT) or magnetic resonance imaging (MRI) scan for objective tumor evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Best Observed Scores | Worst Pain in the Last Week - Baseline | 4 score on a scale | Standard Deviation 3.46 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Best Observed Scores | Composite Pain Interference Score - Baseline | 2.869 score on a scale | Standard Deviation 2.7136 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Best Observed Scores | Worst Pain in the Last Week - Overall Treatment Period | 2.3 score on a scale | Standard Deviation 1 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Best Observed Scores | Least Pain in the Last Week - Overall Treatment Period | 0.8 score on a scale | Standard Deviation 0.91 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Best Observed Scores | Average Pain in the Last Week - Overall Treatment Period | 1.5 score on a scale | Standard Deviation 1.53 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Best Observed Scores | Pain Right Now - Overall Treatment Period | 1.2 score on a scale | Standard Deviation 1.43 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Best Observed Scores | Composite Pain Severity Score - Overall Treatment Period | 1.625 score on a scale | Standard Deviation 1.6737 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Best Observed Scores | Composite Pain Interference Score - Overall Treatment Period | 1.451 score on a scale | Standard Deviation 2.0962 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Best Observed Scores | Worst Pain in the Last Week - Change from Baseline in Overall Treatment Period | -1.4 score on a scale | Standard Deviation 1.75 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Best Observed Scores | Least Pain in the Last Week - Change from Baseline in Overall Treatment Period | -0.7 score on a scale | Standard Deviation 1.35 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Best Observed Scores | Composite Pain Severity Score - Change from Baseline in Overall Treatment Period | -0.75 score on a scale | Standard Deviation 1.0577 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Best Observed Scores | Composite Pain Interference Score - Change from Baseline in Overall Treatment Period | -1.127 score on a scale | Standard Deviation 1.4096 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Best Observed Scores | Least Pain in the Last Week - Baseline | 1.5 score on a scale | Standard Deviation 1.81 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Best Observed Scores | Average Pain in the Last Week - Baseline | 2.4 score on a scale | Standard Deviation 2.13 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Best Observed Scores | Pain Right Now - Baseline | 2 score on a scale | Standard Deviation 1.99 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Best Observed Scores | Composite Pain Severity Score - Baseline | 2.476 score on a scale | Standard Deviation 2.1779 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Best Observed Scores | Average Pain in the Last Week - Change from Baseline in Overall Treatment Period | -0.8 score on a scale | Standard Deviation 1.03 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Best Observed Scores | Pain Right Now - Change from Baseline in Overall Treatment Period | -0.8 score on a scale | Standard Deviation 0.81 |
Secondary
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.
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.
Population: Evaluable Analysis Set consists of subjects who have completed two prime doses of MVA-BN-Brachyury and one booster dose of FPV-Brachyury prior to radiation, have completed radiation therapy, have at least 3 out of 4 booster doses of FPV-Brachyury in 14 weeks after radiation, have both baseline and at least one post-baseline computed tomography (CT) or magnetic resonance imaging (MRI) scan for objective tumor evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Worst Observed Scores | Worst Pain in the Last Week - Baseline | 4.0 score on a scale | Standard Deviation 3.46 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Worst Observed Scores | Average Pain in the Last Week - Baseline | 2.4 score on a scale | Standard Deviation 2.13 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Worst Observed Scores | Pain Right Now - Baseline | 2.0 score on a scale | Standard Deviation 1.99 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Worst Observed Scores | Composite Pain Severity Score - Baseline | 2.476 score on a scale | Standard Deviation 2.1779 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Worst Observed Scores | Composite Pain Interference Score - Baseline | 2.869 score on a scale | Standard Deviation 2.7136 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Worst Observed Scores | Average Pain in the Last Week - Overall Treatment Period | 4.9 score on a scale | Standard Deviation 2.57 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Worst Observed Scores | Pain Right Now - Overall Treatment Period | 5.1 score on a scale | Standard Deviation 2.59 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Worst Observed Scores | Composite Pain Severity Score - Overall Treatment Period | 4.885 score on a scale | Standard Deviation 2.4374 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Worst Observed Scores | Average Pain in the Last Week - Change from Baseline in Overall Treatment Period | 2.2 score on a scale | Standard Deviation 2.59 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Worst Observed Scores | Pain Right Now - Change from Baseline in Overall Treatment Period | 2.9 score on a scale | Standard Deviation 2.69 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Worst Observed Scores | Composite Pain Severity Score - Change from Baseline in Overall Treatment Period | 2.179 score on a scale | Standard Deviation 2.6317 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Worst Observed Scores | Composite Pain Interference Score - Change from Baseline in Overall Treatment Period | 2.152 score on a scale | Standard Deviation 2.9053 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Worst Observed Scores | Least Pain in the Last Week - Baseline | 1.5 score on a scale | Standard Deviation 1.81 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Worst Observed Scores | Worst Pain in the Last Week - Overall Treatment Period | 6.7 score on a scale | Standard Deviation 2.88 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Worst Observed Scores | Least Pain in the Last Week - Overall Treatment Period | 3.9 score on a scale | Standard Deviation 2.77 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Worst Observed Scores | Composite Pain Interference Score - Overall Treatment Period | 5.028 score on a scale | Standard Deviation 2.9807 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Worst Observed Scores | Worst Pain in the Last Week - Change from Baseline in Overall Treatment Period | 2.4 score on a scale | Standard Deviation 3.31 |
| BN-Brachyury Plus Radiation | Baseline and Overall Treatment Period Change From Baseline Brief Pain Improvement-Short Form Worst Observed Scores | Least Pain in the Last Week - Change from Baseline in Overall Treatment Period | 2.0 score on a scale | Standard Deviation 2.73 |
Secondary
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 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.
Population: Evaluable Analysis Set consists of subjects who have completed two prime doses of MVA-BN-Brachyury and one booster dose of FPV-Brachyury prior to radiation, have completed radiation therapy, have at least 3 out of 4 booster doses of FPV-Brachyury in 14 weeks after radation, have both baseline and at least one post-baseline computed tomography (CT) or magnetic resonance imaging (MRI) scan for objective tumor evaluation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BN-Brachyury Plus Radiation | Progression-free Survival (PFS) | NA Weeks |
Other Pre-specified
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.
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.
Population: The Full Analysis Set consists of all subjects who have enrolled and received any dose of MVA-BN Brachyury or FPV-Brachyury.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BN-Brachyury Plus Radiation | Frequencies of Participants With Occurrence, Severity and Seriousness of Adverse Events | Treatment Emergent Adverse Events | 29 Participants |
| BN-Brachyury Plus Radiation | Frequencies of Participants With Occurrence, Severity and Seriousness of Adverse Events | Related Treatment Emergent Adverse Events | 28 Participants |
| BN-Brachyury Plus Radiation | Frequencies of Participants With Occurrence, Severity and Seriousness of Adverse Events | Severe Treatment Emergent Adverse Events | 11 Participants |
| BN-Brachyury Plus Radiation | Frequencies of Participants With Occurrence, Severity and Seriousness of Adverse Events | Severe Related Treatment Emergent Adverse Events | 3 Participants |
| BN-Brachyury Plus Radiation | Frequencies of Participants With Occurrence, Severity and Seriousness of Adverse Events | Serious Adverse Events | 8 Participants |
| BN-Brachyury Plus Radiation | Frequencies of Participants With Occurrence, Severity and Seriousness of Adverse Events | Related Serious Adverse Events | 2 Participants |
| BN-Brachyury Plus Radiation | Frequencies of Participants With Occurrence, Severity and Seriousness of Adverse Events | Adverse Events of Special Interest | 1 Participants |
| BN-Brachyury Plus Radiation | Frequencies of Participants With Occurrence, Severity and Seriousness of Adverse Events | Adverse Events Leading to Discontinuation | 1 Participants |
| BN-Brachyury Plus Radiation | Frequencies of Participants With Occurrence, Severity and Seriousness of Adverse Events | Adverse Events Leading to Death | 1 Participants |
| BN-Brachyury Plus Radiation | Frequencies of Participants With Occurrence, Severity and Seriousness of Adverse Events | Injection Site Reaction Adverse Events | 24 Participants |
Other Pre-specified
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
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.
Population: The Full Analysis Set consists of all subjects who have enrolled and received any dose of MVA-BN Brachyury or FPV-Brachyury
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BN-Brachyury Plus Radiation | Number of Participants With Injection Site Reaction Adverse Events by Preferred Term | Injection site erythema | 6 Participants |
| BN-Brachyury Plus Radiation | Number of Participants With Injection Site Reaction Adverse Events by Preferred Term | Injection site pain | 16 Participants |
| BN-Brachyury Plus Radiation | Number of Participants With Injection Site Reaction Adverse Events by Preferred Term | Injection site induration | 4 Participants |
| BN-Brachyury Plus Radiation | Number of Participants With Injection Site Reaction Adverse Events by Preferred Term | Injection site swelling | 4 Participants |
| BN-Brachyury Plus Radiation | Number of Participants With Injection Site Reaction Adverse Events by Preferred Term | Injection site rash | 3 Participants |
| BN-Brachyury Plus Radiation | Number of Participants With Injection Site Reaction Adverse Events by Preferred Term | Injection site discomfort | 2 Participants |
| BN-Brachyury Plus Radiation | Number of Participants With Injection Site Reaction Adverse Events by Preferred Term | Injection site irritation | 1 Participants |
| BN-Brachyury Plus Radiation | Number of Participants With Injection Site Reaction Adverse Events by Preferred Term | Injection site oedema | 1 Participants |
| BN-Brachyury Plus Radiation | Number of Participants With Injection Site Reaction Adverse Events by Preferred Term | Injection site pruritus | 1 Participants |
Other Pre-specified
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.
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.
Population: The Full Analysis Set consists of all subjects who have enrolled and received any dose of MVA-BN Brachyury or FPV-Brachyury.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Hemoglobin | <= Grade 2 | 29 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Hemoglobin | >= Grade 3 | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Hemoglobin | Missing | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Leukocytes | <= Grade 2 | 29 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Leukocytes | >= Grade 3 | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Leukocytes | Missing | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Lymphocytes | <= Grade 2 | 23 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Lymphocytes | >= Grade 3 | 6 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Lymphocytes | Missing | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Neutrophils | <= Grade 2 | 29 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Platelets | <= Grade 2 | 29 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Platelets | >= Grade 3 | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Platelets | Missing | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Alanine Aminotransferase | <= Grade 2 | 29 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Alanine Aminotransferase | >= Grade 3 | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Alanine Aminotransferase | Missing | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Albumin | <= Grade 2 | 29 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Albumin | >= Grade 3 | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Albumin | Missing | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Alkaline Phosphatase | <= Grade 2 | 29 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Alkaline Phosphatase | >= Grade 3 | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Aspartate Aminotransferase | <= Grade 2 | 29 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Aspartate Aminotransferase | >= Grade 3 | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Aspartate Aminotransferase | Missing | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Bilirubin | <= Grade 2 | 29 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Calcium | <= Grade 2 | 29 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Calcium | >= Grade 3 | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Calcium | Missing | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Creatinine | Missing | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Glucose | <= Grade 2 | 27 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Glucose | >= Grade 3 | 2 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Glucose | Missing | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Magnesium | <= Grade 2 | 15 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Magnesium | >= Grade 3 | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Magnesium | Missing | 14 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Phosphate | <= Grade 2 | 15 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Phosphate | Missing | 14 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Potassium | <= Grade 2 | 29 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Potassium | >= Grade 3 | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Potassium | Missing | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Sodium | <= Grade 2 | 29 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Sodium | >= Grade 3 | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Sodium | Missing | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Neutrophils | >= Grade 3 | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Neutrophils | Missing | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Alkaline Phosphatase | Missing | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Bilirubin | >= Grade 3 | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Bilirubin | Missing | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Creatinine | <= Grade 2 | 29 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Creatinine | >= Grade 3 | 0 Participants |
| BN-Brachyury Plus Radiation | Worst CTCAE Toxicity Grade Shift From Baseline in Laboratory Results (Hematology and Serum Chemistry) | Phosphate | >= Grade 3 | 0 Participants |