This control prevents deadlocks and race conditions. For security, BSI has user password access, 3 types of user access levels, and 36 user permissions (levels of access) that can be set to control access to system functions. BSI provides audit tracking for processes done to specimens , including shipping, returning to inventory, aliquoting, thawing, additives, and other pro cesses. BSI tracks the ancestry of specimens as they are aliquoted, as well as discrepancies and discrepancy resolution for specimens received by the repository. If a specimen goes out of the inventory, the system maintains data associated with the withdra wal request. Vials are labeled with a unique BSI ID printed in both eye- readable and bar -coded format. No patient-specific information is encoded in this ID. Investigators are granted view, input, and withdrawal authority only for their specimens. They may not view specimen data or access specimens for which they have not been authorized. Access to specimen storage is confined to repository staff. Visitors to the repositories are escorted by repository staff at all times. 5.2.2 Protocol Completion/Sample Destruction All specimens obtained in the protocol are used as defined in the protocol. Any specimens remaining at the completion of the protocol will be stored in the conditions described above. The study will remain open so long as sample or data analysis continues. Samples from consenting subjects will be stored until they are no longer of scientific value or until a subject withdraws consent for their continued use, at which time they will be destroyed. Once primary research objectives for the protocol are achieved, intramural researchers can request access to remaining samples , provided they have an IRB -approved protocol and patient consent. The PI will report any loss or destruction of samples to the NCI IRB as soon as he/she is made aware of such loss. The PI will report destroyed samples to the IRB if samples become unsalvageable because of environmental factors such as a broken freezer or lack of dry ice in a 41 Abbreviated Title: Phase I MVA -Brachyury -TRICOM Version Date: September 14, 2016 Confidential shipping container, or if a patient withdraws consent. Samples will also be reported as lost if th ey are lost in transit between facilities or misplaced by a researcher. Freezer problems, lost samples, or other problems associated with samples will also be reported to the IRB, the NCI Clinical Director, and the office of the CCR, NCI. 6 DATA COLLECTION AND EVALUATION 6.1 DATA COLLECTION Data will be entered into the NCI C3D data base. The PI will be responsible for overseeing entry of data into an in-house password protected electronic system and ensuring data accuracy, consistency and timeliness. The principal investigator, associate investigators/research nurses and/or a contracted data manager will assist with the data management efforts. All data obtained during the conduct of the protocol will be kept in secure network drives or in approved alternative sites that comply with NIH security standards. Primary and final analyzed data will have identifiers so that research data can be attributed to an individual human subject participant. End of study procedures: Data will be stored according to HHS, FDA regulations and NIH Intramural Records Retention Schedule as applicable. Loss or destruction of data: Should we become aware that a major breech in our plan to protect subject confidentiality and trial data has occurred, the IRB will be notified. 6.1.1 Case Repor t Forms The site staff will be required to enter in C3D available patient data from a visit no later than 10 business days after the visit is completed. The site staff will respond in a timely fashion to all queries made to the CRF s by the sponsor team and monitors. 6.2 R ESPONSE CRITERIA For the purposes of this study, patients should be re- evaluated for response every 12 weeks . In addition to a baseline scan, confirmatory scans should also be obtained between 4 and 8 weeks following initial documentation of o bjective response or concern of progression, per irRC (per Appendix B, Section 13.2). Response and progression will be evaluated in this study using the new internationa l criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).45 Changes in the largest diameter (unidimensional measurement) of tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria. All patients in this study must be assessed for response to treatment, even if there are major treatment deviation s. 42 Abbreviated Title: Phase I MVA -Brachyury -TRICOM Version Date: September 14, 2016 Confidential Each patient will be assigned one of the following categories: 1) complete response (CR) ; 2) partial response (PR); 3) stable disease (SD); 4) progressive disease (PD); or 5) not evaluable (NE) (death prior to restaging from malignant disease, toxicity, or due to other causes ; or insufficient data). For the purposes of this study, patients will be re- evaluated for response after every 3 planned dosesBecause of direct clinical observation of immune- cell influx into tumor causing tumor enlargement in some patients p rior to sustained response, it has recently been suggested that clinical trials involving the use of immunotherapy use alternative guidelines, called immune -related response criteria (irRC) , to determine radiographic response or progression after therapy. These recommendations have been used in recent clinical trials. One study of 227 subjects with metastatic melanoma showed that the approximately 10% of patients who had PD by modified WHO criteria but either CR, PR, or SD by irRC had overall survival similar to those patients who had SD, PR, or CR by both criteria. The irRC were created using bidimensional measurements (as previously widely used in the WHO criteria). We have taken the concepts of the irRC and combined them with the recently revised RECIST 1.1 45 to come up with the modified irRC used in this protocol (s ee Appendix B in Section 13.2). Consistent with the irRC, the main changes from RECIST 1.1 are (a) a requirement for confirmation of both progression and response by imaging at least 4 weeks after initial imaging and (b) not automatically calling the appearance of new lesions progressive disease if the total measurable tumor burden has not met criteria for progressive disease. For irRC, only index and measurable new lesions are taken into account. At baseline tumor assessment on this trial, target lesions will be measured along the longest axis and the measurements will be summed, called sum of largest diameter (SLD). These lesions must be a minimum of 10 mm per lesion, maximum of 5 target lesions, maximum of 2 per organ system. At each subsequent tumor assessment, the unidimensional measurement of target lesions and of new measureable lesions is added together to provide the total tumor burden. As per the modified definitions in Appendix B (Section 13.2), all responses and progression except SD require confirmation on a consecutive scan at least 4 weeks from the initial observation. Patients who experience rapid disease progression mandating discontinuation of therapy prior to completing 12 weeks of therapy (prior to first restaging) will be considered treatment failures. When possible, the same imaging studies used to define the extent of tumor at baseline upon study entry will be used for restaging. Time to disease progression will be defined as from the first date of therapy until the first notation of clinical or radiographic progression. In the case of SD, follow- up measurements must have met the SD criteria at least once after study entry at a minimum interval (in general, not < 6–8 weeks) defined in the study protocol. Because subjects with non- measurable disease (also called evaluable- only disease) are eligible for enrollment, those subjects will be evaluated with imaging studies for any evidence of disease progression. In these cases, progression will be defined as new lesions found on imaging studies. In the spirit of the irRC, any new lesions in these subjects would then require confirmation of the new lesion on repeat imaging at least 4 weeks later to ensure that new lesi ons were not immune- related phenomena. While we will use the irRC to determine disease progression for treatment purposes, we will also report radiographic responses by RECIST 1.1 (Appendix C, Section 13.3). For study patients with chordoma, modified Choi criteria will be used to evaluate disease progression, stability, or 43 Abbreviated Title: Phase I MVA -Brachyury -TRICOM Version Date: September 14, 2016 Confidential response using MRI and/or CT imaging (Appendix D, Section 13.4) in addition to irRC (RECIST 1.1). Both techniques will be used, while irRC will be used to determine progression for study purposes.