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NCT04315298
11.4.2
Demography and Baseline Characteristics
11.4.2. Demography and Baseline Characteristics Demographic and baseline characteristics will be summarized descriptively by treatment group, and by all patients combined.
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NCT04315298
11.4.3
Efficacy Analyses
11.4.3. Efficacy Analyses The study analysis plan is based on the analysis of 2 populations, an mITT and an ITT population, within specific strata or combinations of strata. Supportive analyses may also be performed using the PPS population.
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NCT04315298
11.4.3.1
Primary Efficacy Analysis
11.4.3.1. Primary Efficacy Analysis Phase 2 portion of study (COVID-19 patients in all disease severity strata): For the Phase 2 portion of the study, the primary efficacy analysis will be a pairwise comparison between sarilumab 400 mg IV and placebo with respect to the primary endpoint of percent change from baseline...
[ "Phase 2 portion of study (COVID-19 patients in all disease severity strata):", "Phase 3 portion of the study (COVID-19 patients in Cohort 1 critical disease severity stratum; and COVID-19 patients in Cohort 2):" ]
NCT04315298
11.4.3.2
Secondary Efficacy Analysis
11.4.3.2. Secondary Efficacy Analysis Analysis for Phase 2 Key Secondary Endpoints: The key secondary endpoint of time-to-improvement (2 points) in clinical status assessment with 7-point ordinal scale will be analyzed for Phase 2 similarly as described above for the Phase 3 primary endpoint in COVID-19 patients (all ...
[ "Analysis for Phase 2 Key Secondary Endpoints:", "Analysis for Phase 3 Key Secondary Endpoints:", "Cohort 1", "Cohort 2", "Analysis for Other Secondary Endpoints (Phase 2 and Phase 3):" ]
NCT04315298
11.4.4
Control of Multiplicity
11.4.4. Control of Multiplicity Phase 2 Portion of the Study (Prior to Adaptations) For the Phase 2 portion of the study, hypothesis test will be conducted for the Phase 2 primary endpoint of percent change from baseline in CRP levels at Day 4 in patients across all disease severity strata in mITT population (ie, high...
[ "Phase 2 Portion of the Study (Prior to Adaptations)", "Phase 3 Portion of the Study (Post-adaptations):" ]
NCT04315298
11.4.5
Safety Analysis
11.4.5. Safety Analysis
[]
NCT04315298
11.4.5.1
Adverse Events
11.4.5.1. Adverse Events Definitions For safety variables, the following observation period is defined: • The on-treatment period is defined as the day from first dose of study drug (Day 1) to study Day 29 (patients who are discharged prior to Day 29 will receive a follow-up phone call to collect data on SAEs (if any)...
[ "Definitions", "Analysis" ]
NCT04315298
11.4.5.2
Other Safety
11.4.5.2. Other Safety Vital Signs Vital signs (temperature, pulse, blood pressure, and respiration rate) will be summarized by baseline and change from baseline to each scheduled assessment time with descriptive statistics. Laboratory Tests Laboratory test results will be summarized by baseline and change from basel...
[ "Vital Signs", "Laboratory Tests" ]
NCT04315298
11.4.5.3
Treatment Exposure
11.4.5.3. Treatment Exposure Exposure to study drug will be examined for each patient. The total number of doses administered to each patient and exposure related parameters (eg, duration of IV infusion, total volume of drug administered etc.) will be analyzed and summarized using descriptive statistics by treatment gr...
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NCT04315298
11.4.5.4
Treatment Compliance
11.4.5.4. Treatment Compliance Treatment compliance in a given patient for this study is defined as the number of fully completed infusions of study drug divided by number of doses administered (applicable, both, to patients who receive only single dose or multiple doses since protocol amendment #4).
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NCT04315298
11.4.6
Pharmacokinetics
11.4.6. Pharmacokinetics
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NCT04315298
11.4.6.1
Analysis of Drug Concentration Data
11.4.6.1. Analysis of Drug Concentration Data The concentrations of sarilumab and sIL-6R over time and selected PK parameters, as appropriate, will be summarized using descriptive statistics. No formal statistical hypothesis testing will be performed.
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NCT04315298
11.4.7
Analysis of Pharmacodynamic and Exploratory Biomarker Data
11.4.7. Analysis of Pharmacodynamic and Exploratory Biomarker Data The concentrations of exploratory PD/Biomarkers over time will be summarized using descriptive statistics and may be reported separately from the CSR.
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NCT04315298
11.5
Timing of Analysis
11.5. Timing of Analysis The timing of the analyses for this study are detailed in Section [6.2.](#page-65-0)
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NCT04315298
11.5.1
Interim Analysis in Phase 3
11.5.1. Interim Analysis in Phase 3 Because of the unmet medical need for effective medicines in this global COVID-19 pandemic situation, interim analyses are planned for efficacy in the Phase 3 portion of the study. The timing of the first interim analysis will be determined once approximately 110 patients in the Phas...
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NCT04315298
11.6
Statistical Considerations Surrounding the Premature Termination of a Study
11.6. Statistical Considerations Surrounding the Premature Termination of a Study If the study is terminated prematurely, only those parameters required for the development program and/or reporting to regulatory authorities will be summarized. Investigator and sponsor responsibilities surrounding the premature terminat...
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NCT04315298
12
QUALITY CONTROL AND QUALITY ASSURANCE
12. QUALITY CONTROL AND QUALITY ASSURANCE In accordance with ICH E6, the sponsor is responsible for quality assurance to ensure that the study is conducted and the data generated, recorded, and reported in compliance with the protocol, GCP, and any applicable regulatory requirement(s). The planned quality assurance and...
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NCT04315298
12.1
Data Management and Electronic Systems
12.1. Data Management and Electronic Systems
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NCT04315298
12.1.1
Data Management
12.1.1. Data Management A data management plan specifying all relevant aspects of data processing for the study (including data validation [quality-checking], cleaning, correcting, releasing) will be maintained and stored at Regeneron (Sponsor). A medical coding plan will specify the processes and the dictionary used f...
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NCT04315298
12.1.2
Electronic Systems
12.1.2. Electronic Systems Electronic systems that may be used to process and/or collect data in this study will include the following: - IWRS system randomization, study drug supply - EDC system data capture Medidata Rave - Statistical Analysis System (SAS) statistical review and analysis - Pharmacovigilance safety da...
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NCT04315298
12.2
Study Monitoring
12.2. Study Monitoring
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NCT04315298
12.2.1
Monitoring of Study Sites
12.2.1. Monitoring of Study Sites The study monitor and/or designee will visit each site prior to enrollment of the first patient, and periodically during the study. This study will use the principles of risk-based monitoring (ICH). This means that the number of visits for any given site may vary based on site risk ind...
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NCT04315298
12.2.2
Source Document Requirements
12.2.2. Source Document Requirements Investigators are required to prepare and maintain adequate and accurate patient records (source documents). The site is responsible to ensure quality within their records and systems and are accountable for ensuring that all source data and CRF data are timely, accurate, and comple...
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NCT04315298
12.2.3
Case Report Form Requirements
12.2.3. Case Report Form Requirements Study data obtained in the course of the clinical study will be recorded on electronic Case Report Forms (CRFs) within the EDC system by trained site personnel. All required CRFs must be completed for each and every patient enrolled in the study. The investigator must ensure the ac...
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NCT04315298
12.3
Audits and Inspections
12.3. Audits and Inspections This study may be subject to a quality assurance audit or inspection by the sponsor or regulatory authorities. Should this occur, the investigator is responsible for: - Informing the sponsor of a planned inspection by the authorities as soon as notification is received, and authorizing the ...
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NCT04315298
12.4
Study Documentation
12.4. Study Documentation
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NCT04315298
12.4.1
Certification of Accuracy of Data
12.4.1. Certification of Accuracy of Data A declaration assuring the accuracy and content of the data recorded on the eCRF must be signed electronically by the investigator. This signed declaration accompanies each set of patient final eCRF that will be provided to the sponsor.
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NCT04315298
12.4.2
Retention of Records
12.4.2. Retention of Records The investigator must retain all essential study documents, including ICFs, source documents, investigator copies of CRFs, and drug accountability records for at least 15 years following the completion or discontinuation of the study, or longer, if a longer period is required by relevant re...
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NCT04315298
13
ETHICAL AND REGULATORY CONSIDERATIONS
13. ETHICAL AND REGULATORY CONSIDERATIONS
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NCT04315298
13.1
Good Clinical Practice Statement
13.1. Good Clinical Practice Statement It is the responsibility of both the sponsor and the investigator(s) to ensure that this clinical study will be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with the ICH guidelines for GCP and ap...
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NCT04315298
13.2
Informed Consent
13.2. Informed Consent The principles of informed consent are described in ICH guidelines for GCP. The ICF used by the investigator must be reviewed and approved by the sponsor prior to submission to the appropriate IRB. A copy of the IRB -approved ICF and documentation of approval must be provided to the sponsor befor...
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NCT04315298
13.3
Patients Confidentiality and Data Protection
13.3. Patients Confidentiality and Data Protection The investigator must take all appropriate measures to ensure that the anonymity of each study patient will be maintained. Patients should be identified by a patient identification number only, on CRFs or other documents submitted to the sponsor. Documents that will no...
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NCT04315298
13.4
Institutional Review Board
13.4. Institutional Review Board An appropriately constituted IRB, as described in ICH guidelines for GCP, must review and approve: - The protocol, ICF, and any other materials to be provided to the patients (eg, advertising) before any patient may be enrolled in the study - Any amendment or modification to the study p...
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NCT04315298
13.5
Clinical Study Data Transparency
13.5. Clinical Study Data Transparency Final study results will be published on a public clinical trial website according to applicable local guidelines and regulations. Treatment codes will be disseminated to each investigation site thereafter.
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NCT04315298
14
PROTOCOL AMENDMENTS
14. PROTOCOL AMENDMENTS The sponsor may not implement a change in the design of the protocol or ICF without an IRB-approved amendment. Where required per local legislation, regulatory authority approval will also be sought.
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NCT04315298
15
PREMATURE TERMINATION OF THE STUDY OR CLOSE-OUT OF A SITE
15. PREMATURE TERMINATION OF THE STUDY OR CLOSE-OUT OF A SITE
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NCT04315298
15.1
Premature Termination of the Study
15.1. Premature Termination of the Study The sponsor has the right to terminate the study prematurely. Reasons may include efficacy, safety, or futility, among others. Should the sponsor decide to terminate the study, the investigator(s) will be notified in writing.
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NCT04315298
15.2
Close-out of a Site
15.2. Close-out of a Site The sponsor and the investigator have the right to close-out a site prematurely. Investigator's Decision The investigator must notify the sponsor of a desire to close-out a site in writing, providing at least 30 days' notice. The final decision should be made through mutual agreement with the...
[ "Investigator's Decision", "Sponsor's Decision" ]
NCT04315298
16
CONFIDENTIALITY
16. CONFIDENTIALITY Confidentiality of information is provided as a separate agreement.
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NCT04315298
17
FINANCING AND INSURANCE
17. FINANCING AND INSURANCE Financing and insurance information is provided as a separate agreement.
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NCT04315298
18
PUBLICATION POLICY
18. PUBLICATION POLICY Publication rights and procedures will be outlined in a separate clinical study agreement.
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NCT04315298
19
REFERENCES
19. REFERENCES Actemra® [package insert]. 2010. Genentech, Inc., South San Francisco, CA. Centers for Disease Control and Prevention (CDC). Interim Guidance for Discontinuation of Transmission-Based Precautions and Disposition of Hospitalized Patients with COVID-19. [https://www.cdc.gov/coronavirus/2019-ncov/hcp/dispos...
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NCT04315298
20
INVESTIGATOR'S AGREEMENT
20. INVESTIGATOR'S AGREEMENT I have read the attached protocol: An adaptive phase 2/3, Randomized, Double-Blind, Placebo-Controlled Study Assessing Efficacy and Safety of Sarilumab for Hospitalized Patients with COVID-19 and agree to abide by all provisions set forth therein. I agree to comply with the current Internat...
[ "SIGNATURE OF SPONSOR'S RESPONSIBLE OFFICERS", "Signature Page for VV-RIM-00114290 v1.0" ]
NCT04326231
1
Study Device Description
1 Study Device Description The study device is an investigational digital therapy that uses Augmented Realitybased social behavioral therapy, as an adjunct to standard outpatient applied behavioral analysis therapy, to improve adaptive behavior, specifically social skills in children with Autism Spectrum Disorder. The ...
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NCT04326231
2
Study Objectives
2 Study Objectives Cognoa will measure usability, engagement with the device, and changes in parentreported socialization during a 4-week period of intervention at home with the Cognoa ASD therapeutic device.
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NCT04326231
2.1
Study Purpose
2.1 Study Purpose The purpose of this study is to evaluate the safety, effectiveness and usability of the device smartphone application, and Quick Start Guide) with intended users.
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NCT04326231
3
Study Outcome Measures
3 Study Outcome Measures - Usability assessment of Cognoa ASD Therapeutic Device - Change in scores on the Vineland-3 domain level caregiver report social skills and relationships from baseline to 4 week measurement
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NCT04326231
4
Study Duration
4 Study Duration Duration of subject participation is approximately 4 weeks. Total study duration is approximately 12 weeks.
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NCT04326231
5
Study Population
5 Study Population
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NCT04326231
5.1
Study participant Recruitment and Selection
5.1 Study participant Recruitment and Selection Up to 30 caregivers and children diagnosed with ASD ages > 3 to < 9 years of age will be recruited from across the U.S. Only subjects who meet all eligibility criteria will be enrolled into the study. Eligibility will be determined during a scheduled phone call by Cognoa ...
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NCT04326231
5.2
Inclusion Criteria:
5.2 Inclusion Criteria: - Functional English language capability in the home environment. - Parent, Guardian, or legal authorized representative (LAR) must be able to read, understand and sign the Informed Consent Form (ICF) - Female or Male, > 3 to < 9 years of age and parent/caregiver - Diagnosis of Autism Spectrum D...
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NCT04326231
5.3
Exclusion Criteria:
5.3 Exclusion Criteria: - Participants with any other medical, behavioral, or developmental condition that in the opinion of the investigator may confound study data/assessments. - Participants with planned extensive travel (more than 1 week) during the course of the 4-week intervention time period. - Participants with...
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NCT04326231
6
Study Assessment
6 Study Assessment Parents who consent will be given access to the study device through its caregiver and child-facing smartphone app that provides therapeutic content. In order to access the study device app, parents will be provided access to two other apps. The first is Testflight. TestFlight is an online service fo...
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NCT04326231
6.1
Training
6.1 Training The investigator and site research staff will be trained on the protocol and on all study procedures. Monitoring of the site will occur to evaluate the progress of the study, verify the accuracy and completeness of data, assure that all protocol requirements, applicable FDA regulations and investigator obl...
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NCT04326231
6.2
Usability Metrics
6.2 Usability Metrics - Average duration of sessions using the device - Total number of sessions completed - Ratings of fatigue - Ratings of frustration - Ratings of irritability - Ratings of comprehension of Instructions for caregivers - Ratings of comprehension of Instructions for children - Ratings of user app burde...
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NCT04326231
7
Data Collection and Storage
7 Data Collection and Storage Data collection will be completed using electronic and/or paper report forms provided by Cognoa and data will be recorded into Cognoa dedicated study data repository. Data fields will include: - Date of ICF - Participant demographics - Device usage metrics - VABS-3 caregiver report social ...
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NCT04326231
8
Adverse Events 8.1 Definitions
8 Adverse Events 8.1 Definitions An adverse event (AE) is defined as untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in subjects, device users or other persons, whether or not it is related to the investigational medical device. Expected adv...
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NCT04326231
8.2
Recording AEs/ADEs and SAEs/SADEs
8.2 Recording AEs/ADEs and SAEs/SADEs All reported AEs/SAEs or ADEs/SADEs will be: (1) evaluated and must be recorded in the participant's study case report forms (CRFs); (2) monitored and tracked from the time of the first treatment. At each contact with the participant, the investigator must seek information on AEs/A...
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NCT04326231
8.3
Follow-up of participants after AEs
8.3 Follow-up of participants after AEs All reported AEs/ADEs/SAEs/SADEs should be followed until resolution or until the participant's participation in the study ends. Resolutions of AEs/ADEs/SAEs/SADEs are to be documented on the appropriate CRFs. All ADEs that result in permanent discontinuation from this clinical t...
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NCT04326231
9
Potential Risks/Benefits
9 Potential Risks/Benefits
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NCT04326231
9.1
Potential Risks
9.1 Potential Risks Risks related to the study are expected to be minimal. Physical risks for participating in the study are expected to be minimal. Children may experience some fatigue holding the device during intervention sessions. Children may also experience some irritation and frustration while using the device. ...
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NCT04326231
9.2
Potential Benefits
9.2 Potential Benefits The subjects may or may not benefit from being enrolled in the study.
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NCT04326231
10
Study Management and Administrative Considerations
10 Study Management and Administrative Considerations
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NCT04326231
10.1
Informed Consent
10.1 Informed Consent The investigator or the investor's designee will inform all subjects regarding the purpose of the study and expected duration, as well as any potential risks and benefits that may result from participation. The subjects shall be informed by the investigator or investor's designee that they are fre...
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NCT04326231
10.2
Participant Confidentiality
10.2 Participant Confidentiality This study preserves the confidentiality of all subjects. The following safeguards will be in place to protect the privacy of the individuals who are the subjects of the health information to be used in the research and the confidentiality of that information: The subjects will be infor...
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NCT04326231
10.3
Financial Considerations
10.3 Financial Considerations Subject Compensation: The subject's caregiver will be compensated up to \$200 for their participation. \$100 for completion of the baseline assessment and \$100 at the conclusion of the study following the final assessment and completion of the 4 weeks of device use 4-6 times a week.
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NCT04326231
10.4
Study Discontinuation
10.4 Study Discontinuation Cognoa, Inc. (the sponsor) has the right to terminate this study at any time. Reasons for terminating the study may include, but are not limited to, the following: subject enrollment is unsatisfactory; number of protocol deviations is unacceptable; data is inaccurate or incomplete; questionab...
[ "References" ]
NCT04339062
1
OBJECTIVES
1. OBJECTIVES
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NCT04339062
1.1
Study Design
1.1 Study Design This is an open-label, two cohort, phase I/II study of immune checkpoint blockade with cemiplimab in patients with advanced cutaneous squamous cell carcinoma (cSCC) who have previously undergone an allogeneic hematopoietic stem cell transplant (HSCT) or renal allograft transplantation. Patients are div...
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NCT04339062
1.2
Primary Objectives
1.2 Primary Objectives To determine the safety and toxicity of immunotherapy in advanced cutaneous squamous cell carcinoma (cSCC) patients having undergone prior hematopoietic stem cell or renal transplant.
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NCT04339062
1.3
Secondary Objectives
1.3 Secondary Objectives To evaluate the anti-tumor activity and survival benefit in advanced cSCC patients receiving immunotherapy despite a history of transplant: - To estimate progression-free survival (PFS) and overall survival (OS) - To estimate overall response rate (ORR) - To estimate duration of therapeutic res...
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NCT04339062
2
BACKGROUND
2. BACKGROUND
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NCT04339062
2.1
Study Disease(s)
2.1 Study Disease(s) Cutaneous squamous cell carcinoma (cSCC) is diagnosed in hundreds of thousands of patients each year in the United States and continues to increase due to our aging and sun-exposed population [1]. Risk factors for cSCC include sun or ultraviolet (UV) radiation exposure, advanced age, and immunosupp...
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NCT04339062
2.2
IND Agents
2.2 IND Agents
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NCT04339062
2.2.1
Cemiplimab
2.2.1 Cemiplimab
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NCT04339062
2.2.1.1
Mechanism of action and pharmacology
2.2.1.1 Mechanism of action and pharmacology Cemiplimab-rwlc is a recombinant human IgG4 monoclonal antibody that inhibits programmed death-1 (PD-1) activity by binding to PD-1 and blocking the interactions with the ligands PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of immune response, including antitu...
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NCT04339062
2.2.1.2
Clinical safety
2.2.1.2 Clinical safety Cemiplimab was investigated in a phase I/II open-label trial in advanced cSCC patients where the most common adverse events were diarrhea (27% of patients), fatigue (24%), nausea (17%), constipation (15%), and skin rash (15%) [10]. Four patients (7% of the initial study) discontinued therapy due...
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NCT04339062
2.2.1.3
Clinical efficacy
2.2.1.3 Clinical efficacy In the pivotal phase I/II trial of cemiplimab in advanced or metastatic cSCC patients the overall response rate was 47% and the rate of durable disease control was 61% with 4 complete responses and 24 partial responses [10]. Median time to an observed response was 1.9 months (range, 1.7-6.0 mo...
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NCT04339062
2.2.2
Mechanistic target of rapamycin (mTOR) inhibition: Everolimus and Sirolimus
2.2.2 Mechanistic target of rapamycin (mTOR) inhibition: Everolimus and Sirolimus
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NCT04339062
2.2.2.1
Mechanism of action and pharmacology
2.2.2.1 Mechanism of action and pharmacology Everolimus is a macrolide immunosuppressant and a mechanistic target of rapamycin (mTOR) inhibitor which has antiproliferative and antiangiogenic properties. It reduces protein synthesis and cell proliferation by binding to the FK binding protein-12 (FKBP-12), an intracellul...
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NCT04339062
2.2.2.2
Clinical safety
2.2.2.2 Clinical safety The dose and schedule of everolimus for clinical use was established in a study of 55 advanced solid tumor patients using a dose escalation scheme whereby dose limiting toxicity (DLT) of stomatitis, neutropenia, and hyperglycemia yielded a recommended 10 mg daily dose for further development [24...
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NCT04339062
2.2.2.3
Clinical efficacy
2.2.2.3 Clinical efficacy Everolimus has demonstrated efficacy as immunosuppression following de-novo lung transplantation as noted in an investigator-sponsored, single institution study from Germany in 2016 [30]. Forty-three patients were randomized to everolimus (over mycophenolate mofetil [MMF]) and the everolimus g...
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NCT04339062
2.2.3
Combining Cemiplimab and mTOR inhibition
2.2.3 Combining Cemiplimab and mTOR inhibition
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NCT04339062
2.2.3.1
Preclinical efficacy
2.2.3.1 Preclinical efficacy While no data have yet reported the safety or efficacy of PD-1/L1 blockade used in combination with everolimus or mTOR inhibition, therapeutic efficacy in the early preclinical setting suggests that combining these agents could offer enhanced anti-tumor effect [31]. Hirayama and colleagues ...
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NCT04339062
2.3
Rationale
2.3 Rationale Until 2018 there were no systemic therapies approved for the treatment of advanced or metastatic cSCC, despite its significant cosmetic and functional morbidity and overall poor prognosis. However, UV radiation leading to a rich mutational burden in this disease proved a promising attribute when consideri...
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NCT04339062
2.4
Correlative Studies Background
2.4 Correlative Studies Background Clinical trial administration of immune checkpoint blockade among prior transplant recipients with a modified immunosuppressive regimen will provide a unique opportunity to understand immunology within this high-risk and vulnerable population. Peripheral blood and tumor tissue biopsy ...
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NCT04339062
3
PARTICIPANT SELECTION
3. PARTICIPANT SELECTION
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NCT04339062
3.1
Eligibility Criteria
3.1 Eligibility Criteria - 3.1.1 Patients must have histologically confirmed, advanced or metastatic cutaneous squamous cell carcinoma (cSCC) with 1 or more measurable lesions (greater than or equal to 1 cm). - 3.1.2 A history of either (Cohort 1) allogeneic hematopoietic stem cell transplant (allo-HSCT) and ≥ 2 years ...
[ "institutional normal (CKD-EPI equation)." ]
NCT04339062
3.2
Exclusion Criteria
3.2 Exclusion Criteria Participants who have had chemotherapy or radiotherapy within 1 week prior to entering the study or those who have unresolved toxicities from prior anti-cancer therapy more than 2 weeks earlier, defined as not resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Eve...
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NCT04339062
3.3
Inclusion of Women and Minorities
3.3 Inclusion of Women and Minorities Both men and women of all races and ethnic groups are eligible for this trial.
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NCT04339062
4
REGISTRATION PROCEDURES
4. REGISTRATION PROCEDURES
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NCT04339062
4.1
General Guidelines for DF/HCC Institutions
4.1 General Guidelines for DF/HCC Institutions Institutions will register eligible participants in the Clinical Trials Management System (CTMS) OnCore. Registrations must occur prior to the initiation of any protocol-specific therapy or intervention. Any participant not registered to the protocol before protocol-specif...
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NCT04339062
4.1
Registration Process for DF/HCC Institutions
4.1 Registration Process for DF/HCC Institutions Applicable DF/HCC policy (REGIST-101) must be followed.
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NCT04339062
5
TREATMENT PLAN
5. TREATMENT PLAN While accrual is expected to be slow, we will approve two patients to enroll into to each cohort at a time to monitor toxicity appropriately. Eligibility and exclusion criteria are provided in Section 3. These criteria will be assessed within 14 days prior to study registration to establish eligibilit...
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NCT04339062
5.1
Treatment Regimen
5.1 Treatment Regimen No investigational or commercial agents or therapies other than those described below may be administered with the intent to treat the participant's malignancy during the course of treatment. Treatment cycles will be 21 days throughout the protocol. Patients are assigned to one of two predetermine...
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NCT04339062
5.1.1
Cemiplimab Treatment (same for both Cohort 1 and Cohort 2)
5.1.1 Cemiplimab Treatment (same for both Cohort 1 and Cohort 2) Cemiplimab (350 mg IV) will be administered in the outpatient setting at the beginning of the study (following a prednisone lead-in in Cohort 2 only) and will be dosed every 21 days (3 weeks) until disease progression, intolerability, or limiting toxicity...
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NCT04339062
5.1.2
Dynamic Immunosuppression (Cohort 2 only)
5.1.2 Dynamic Immunosuppression (Cohort 2 only) Patients in Cohort 2 with a history of prior renal transplant will need to transition to dynamic immunosuppression with either sirolimus or everolimus (mTOR inhibitors) during a lead-in phase of the study, 7-10 days prior to receiving the first dose of cemiplimab. If the ...
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NCT04339062
5.1.2.1
mTOR inhibitor and Prednisone Lead-in
5.1.2.1 mTOR inhibitor and Prednisone Lead-in Patients in Cohort 2 will start mTOR inhibition with either sirolimus or everolimus at least 7-10 days prior to receiving the first dose of cemiplimab (Cycle 1, Day 1). The choice of agent, starting dose, and titration of mTOR dosing to optimal blood levels is at the discre...
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NCT04339062
5.1.2.2
mTOR inhibitor and Prednisone dosing Scheme After Lead-in
5.1.2.2 mTOR inhibitor and Prednisone dosing Scheme After Lead-in In Cohort 2, after the patient starts mTOR inhibition and receives 40 mg of prednisone as their lead-in to the first dose of cemiplimab, the patient then receives 40 mg of prednisone orally on the day of cemiplimab treatment (Cycle 1, Day 1) and for 2 da...
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NCT04339062
5.1.2.3
Antibiotic prophylaxis on immunosuppression
5.1.2.3 Antibiotic prophylaxis on immunosuppression Prophylactic antimicrobial and antiviral use is permitted while patients are receiving mTOR inhibition and prednisone as part of dynamic immunosuppression. Dose adjustments of mTOR inhibitors based on trough levels throughout the study do not impact the timing or dosi...
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