protocol_id stringclasses 263
values | section_number stringlengths 1 12 | title stringlengths 1 1.88k | content stringlengths 0 866k | merged_titles listlengths 0 491 |
|---|---|---|---|---|
NCT04102098 | 4.3.1.2 | Bevacizumab | 4.3.1.2 Bevacizumab The bevacizumab drug product will be supplied by the Sponsor as a sterile liquid in single-use, 16-mL, preservative-free glass vials that contain 400 mg of bevacizumab (25 mg/mL). For information on the formulation and handling of bevacizumab, see the pharmacy manual and the Bevacizumab Investigator... | [] |
NCT04102098 | 4.3.2 | Study Treatment Dosage, Administration, and Compliance | 4.3.2 Study Treatment Dosage, Administration, and Compliance The treatment regimens are summarized in Section 3.1. Atezolizumab will be administered first followed by bevacizumab, with a minimum of 5 minutes between dosing. Patients will receive treatment as described in Sections 4.3.2.1 and 4.3.2.2. Treatment must be ... | [] |
NCT04102098 | 4.3.2.1 | Atezolizumab | 4.3.2.1 Atezolizumab Atezolizumab will be administered by IV infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle. Treatment duration is described in Section 3.1. Administration of atezolizumab will be performed in a monitored setting where there is immediate access to trained personnel and adequate equipm... | [
"Table 5 Administration of First and Subsequent Atezolizumab Infusions",
"No premedication is permitted prior to the atezolizumab infusion.",
"First Infusion Subsequent Infusions"
] |
NCT04102098 | 4.3.2.2 | Bevacizumab | 4.3.2.2 Bevacizumab Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle. Treatment duration is described in Section 3.1. Administration of bevacizumab will be performed in a monitored setting where there is immediate access to trained personnel and adequate equipment and ... | [
"Table 6 Administration of First and Subsequent Bevacizumab Infusions",
"First Infusion Subsequent Infusions No premedication is permitted prior to the bevacizumab infusion. Vital signs (pulse rate, respiratory rate, blood pressure, and temperature) should be measured within 60 minutes prior to the infusion. a Be... |
NCT04102098 | 4.3.3 | Investigational Medicinal Product Accountability | 4.3.3 Investigational Medicinal Product Accountability All IMPs required for completion of this study (atezolizumab and bevacizumab) will be provided by the Sponsor. The study site will acknowledge receipt of IMPs supplied by the Sponsor using the IxRS to confirm the shipment condition and content. Any damaged shipment... | [] |
NCT04102098 | 4.3.4 | Continued Access to Atezolizumab and Bevacizumab | 4.3.4 Continued Access to Atezolizumab and Bevacizumab The Sponsor will offer continued access to Roche IMPs (atezolizumab and bevacizumab) free of charge to eligible patients in accordance with the Roche Global Policy on Continued Access to Investigational Medicinal Product, as outlined below. A patient will be eligib... | [] |
NCT04102098 | 4.4 | CONCOMITANT THERAPY | 4.4 CONCOMITANT THERAPY Concomitant therapy consists of any medication (e.g., prescription drugs, over-the-counter drugs, vaccines, herbal or homeopathic remedies, nutritional supplements) used by a patient in addition to protocol-mandated treatment from 7 days prior to Day 1 of Cycle 1 to the treatment/surveillance di... | [] |
NCT04102098 | 4.4.1 | Permitted Therapy | 4.4.1 Permitted Therapy Patients are permitted to use the following therapies during the study: - Oral contraceptives with a failure rate of 1% per year (see Section 4.1.1) - Hormone-replacement therapy - Vaccinations (such as influenza, COVID-19) Live, attenuated vaccines are not permitted (see Section 4.4.3) - Megest... | [] |
NCT04102098 | 4.4.2 | Cautionary Therapy for Atezolizumab-Treated Patients | 4.4.2 Cautionary Therapy for Atezolizumab-Treated Patients | [] |
NCT04102098 | 4.4.2.1 | Corticosteroids, Immunosuppressive Medications, and Tumor Necrosis Factor- Inhibitors | 4.4.2.1 Corticosteroids, Immunosuppressive Medications, and Tumor Necrosis Factor- Inhibitors Systemic corticosteroids, immunosuppressive medications, and TNF- inhibitors may attenuate potential beneficial immunologic effects of treatment with atezolizumab. Therefore, in situations in which systemic corticosteroids, im... | [] |
NCT04102098 | 4.4.2.2 | Herbal Therapies | 4.4.2.2 Herbal Therapies Concomitant use of herbal therapies, including traditional Chinese medicine, is not recommended because their pharmacokinetics, safety profiles, and potential drugdrug interactions are generally unknown. However, herbal therapies not intended for the treatment of cancer (see Section 4.4.3) may ... | [] |
NCT04102098 | 4.4.3 | Prohibited Therapy | 4.4.3 Prohibited Therapy Any concomitant therapy intended for the treatment of cancer, whether health authorityapproved or experimental, is prohibited for various time periods prior to Day 1 of Cycle 1 (depending on the anticancer agent; see Section 4.1.2), during study treatment/active surveillance, and during long-te... | [] |
NCT04102098 | 4.5 | STUDY ASSESSMENTS | 4.5 STUDY ASSESSMENTS The schedule of activities to be performed in the study is provided in Appendix 1. A schedule of activities for patients randomized to Arm B who cross over to treatment with atezolizumab plus bevacizumab is provided in Appendix 2. All activities should be performed and documented for each patient.... | [] |
NCT04102098 | 4.5.1 | Informed Consent Forms and Screening Log | 4.5.1 Informed Consent Forms and Screening Log Written informed consent for participation in the study must be obtained before performing any study-related procedures (including screening evaluations). Informed Consent Forms for enrolled patients and for patients who are not subsequently enrolled will be maintained at ... | [] |
NCT04102098 | 4.5.2 | Medical History, Baseline Conditions, Concomitant Medication, and Demographic Data | 4.5.2 Medical History, Baseline Conditions, Concomitant Medication, and Demographic Data Medical history, including clinically significant diseases, surgeries, cancer history (including prior cancer therapies and procedures), reproductive status, smoking history, and use of alcohol and drugs of abuse, will be recorded ... | [] |
NCT04102098 | 4.5.3 | Physical Examinations | 4.5.3 Physical Examinations A complete physical examination, performed at screening, should include an evaluation of the head, eyes, ears, nose, and throat, and the cardiovascular, dermatologic, musculoskeletal, respiratory, GI, genitourinary, and neurologic systems. Any abnormality identified at baseline should be rec... | [] |
NCT04102098 | 4.5.4 | Vital Signs | 4.5.4 Vital Signs Vital signs will include measurements of respiratory rate, pulse rate, systolic and diastolic BP, and temperature. Abnormalities observed at baseline should be recorded on the General Medical History and Baseline Conditions eCRF. At subsequent visits, any new or worsened clinically significant abnorma... | [] |
NCT04102098 | 4.5.5 | Imaging Assessments | 4.5.5 Imaging Assessments Patients will undergo imaging assessments at screening, every 12 weeks for the first 3 years following randomization and every 24 weeks thereafter, regardless of treatment delays, until IRF-confirmed disease recurrence or until the end of Year 7 after randomization, whichever occurs first even... | [
"Imaging for Patients in Arm B Who Cross Over to Treatment with Atezolizumab plus Bevacizumab"
] |
NCT04102098 | 4.5.6 | Laboratory, Biomarker, and Other Biological Samples | 4.5.6 Laboratory, Biomarker, and Other Biological Samples Samples for the following laboratory tests will be sent to the study site's local laboratory for analysis: - Hematology: WBC count, RBC count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphoc... | [] |
NCT04102098 | 4.5.7 | Electrocardiograms | 4.5.7 Electrocardiograms An ECG is required at screening and when clinically indicated. ECGs for each patient should be obtained from the same machine wherever possible. Lead placement should be as consistent as possible. ECG recordings must be performed after the patient has been resting in a supine position for at le... | [] |
NCT04102098 | 4.5.8 | Patient-Reported Outcomes | 4.5.8 Patient-Reported Outcomes To more fully characterize the clinical profile of atezolizumab in combination with bevacizumab, patient-reported outcome (PRO) data will be obtained through use of the following instruments: the IL42–EORTC QLQ-C30 (Reduced) and the EQ-5D-5L. Refer to Appendix 1 for the frequency and tim... | [] |
NCT04102098 | 4.5.8.1 | Data Collection Methods for Patient-Reported Outcomes | 4.5.8.1 Data Collection Methods for Patient-Reported Outcomes The PRO instruments will be completed at the clinic or by means of a telephone call at specified timepoints during the study (see Appendix 1). To ensure instrument validity and that data standards meet health authority requirements, questionnaires must be co... | [] |
NCT04102098 | 4.5.8.2 | Description of Patient-Reported Outcomes Instruments IL42–EORTC QLQ-C30 (Reduced) | 4.5.8.2 Description of Patient-Reported Outcomes Instruments IL42–EORTC QLQ-C30 (Reduced) The IL42–EORTC QLQ-C30 (Reduced) is a reduced version of the validated, reliable EORTC QLQ-C30, self-report measure (Aaronson et al. 1993; Fitzsimmons et al. 1999). This reduced version contains the validated patient functioning (... | [
"EQ-5D-5L"
] |
NCT04102098 | 4.5.9 | Blood Samples for Whole Genome Sequencing or Whole Exome Sequencing (Patients at Participating Sites) | 4.5.9 Blood Samples for Whole Genome Sequencing or Whole Exome Sequencing (Patients at Participating Sites) At participating sites, blood samples will be collected for DNA extraction to enable WGS or WES to identify variants that are predictive of response to study drug, are associated with progression to a more severe... | [] |
NCT04102098 | 4.5.10 | Optional Samples for Research Biosample Repository 4.5.10.1 Overview of the Research Biosample Repository | 4.5.10 Optional Samples for Research Biosample Repository 4.5.10.1 Overview of the Research Biosample Repository The Research Biosample Repository (RBR) is a centrally administered group of facilities used for the long-term storage of human biological specimens, including body fluids, solid tissues, and derivatives the... | [] |
NCT04102098 | 4.5.10.2 | Approval by the Institutional Review Board or Ethics Committee | 4.5.10.2 Approval by the Institutional Review Board or Ethics Committee Collection, storage, and analysis of RBR samples is contingent upon the review and approval of the exploratory research and the RBR portion of the Informed Consent Form by each site's IRB/EC and, if applicable, an appropriate regulatory body. If a ... | [] |
NCT04102098 | 4.5.10.3 | Sample Collection | 4.5.10.3 Sample Collection The following samples will be stored in the RBR and used for research purposes, including, but not limited to, research on biomarkers related to atezolizumab and bevacizumab, HCC, diseases, or drug safety: Leftover blood, serum, plasma, and tumor tissue samples (with the exception of remainin... | [] |
NCT04102098 | 4.5.10.4 | Confidentiality | 4.5.10.4 Confidentiality The RBR samples and associated data will be labeled with a unique patient identification number. Patient medical information associated with RBR samples is confidential and may be disclosed to third parties only as permitted by the Informed Consent Form (or separate authorization for use and di... | [] |
NCT04102098 | 4.5.10.5 | Consent to Participate in the Research Biosample Repository | 4.5.10.5 Consent to Participate in the Research Biosample Repository The Informed Consent Form will contain a separate section that addresses participation in the RBR. The investigator or authorized designee will explain to each patient the objectives, methods, and potential hazards of participation in the RBR. Patient... | [] |
NCT04102098 | 4.5.10.6 | Withdrawal from the Research Biosample Repository | 4.5.10.6 Withdrawal from the Research Biosample Repository Patients who give consent to provide RBR samples have the right to withdraw their consent at any time for any reason. After withdrawal of consent, any remaining samples will be destroyed or will no longer be linked to the patient. However, if RBR samples have b... | [] |
NCT04102098 | 4.5.10.7 | Monitoring and Oversight | 4.5.10.7 Monitoring and Oversight The RBR samples will be tracked in a manner consistent with Good Clinical Practice by a quality-controlled, auditable, and appropriately validated laboratory information management system, to ensure compliance with data confidentiality as well as adherence to authorized use of samples ... | [] |
NCT04102098 | 4.6 | TREATMENT, PATIENT, STUDY, AND SITE DISCONTINUATION | 4.6 TREATMENT, PATIENT, STUDY, AND SITE DISCONTINUATION | [] |
NCT04102098 | 4.6.1 | Study Treatment Discontinuation | 4.6.1 Study Treatment Discontinuation Patients must permanently discontinue study treatment (atezolizumab and bevacizumab) if they experience any of the following: - Intolerable toxicity related to study treatment, including development of an immune-mediated adverse event determined by the investigator to be unacceptab... | [] |
NCT04102098 | 4.6.2 | Patient Discontinuation from the Study | 4.6.2 Patient Discontinuation from the Study Patients have the right to voluntarily withdraw from the study at any time for any reason. In addition, the investigator has the right to withdraw a patient from the study at any time. Reasons for patient discontinuation from the study may include, but are not limited to, th... | [] |
NCT04102098 | 4.6.3 | Study Discontinuation | 4.6.3 Study Discontinuation 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: - The incidence or severity of adverse events in this or other studies indicates a potential health hazard to patients. - Patient enrollment is... | [] |
NCT04102098 | 4.6.4 | Site Discontinuation | 4.6.4 Site Discontinuation The Sponsor has the right to close a site at any time. Reasons for closing a site may include, but are not limited to, the following: - Excessively slow recruitment - Poor protocol adherence - Inaccurate or incomplete data recording - Non-compliance with the International Council for Harmonis... | [] |
NCT04102098 | 5 | ASSESSMENT OF SAFETY | 5. ASSESSMENT OF SAFETY | [] |
NCT04102098 | 5.1 | SAFETY PLAN | 5.1 SAFETY PLAN The safety plan for patients in this study is based on clinical experience with atezolizumab and bevacizumab in completed and ongoing studies. The anticipated important safety risks are outlined below (see Sections 5.1.15.1.3). Measures will be taken to ensure the safety of patients participating in thi... | [] |
NCT04102098 | 5.1.1 | Risks Associated with Atezolizumab | 5.1.1 Risks Associated with Atezolizumab Atezolizumab has been associated with risks such as the following: IRRs and immune-mediated hepatitis, pneumonitis, colitis, pancreatitis, diabetes mellitus, hypothyroidism, hyperthyroidism, adrenal insufficiency, hypophysitis, Guillain-Barré syndrome, myasthenic syndrome or mya... | [] |
NCT04102098 | 5.1.2 | Risks Associated with Bevacizumab | 5.1.2 Risks Associated with Bevacizumab Bevacizumab has been associated with risks such as the following: GI perforations, all-bladder perforation, hemorrhage, pulmonary hemorrhage, arterial thromboembolic events (ATE), fistulae, wound-healing complications, hypertension, congestive heart failure (CHF), cardiac disorde... | [] |
NCT04102098 | 5.1.3 | Risks Associated with Combination Use of Atezolizumab and Bevacizumab | 5.1.3 Risks Associated with Combination Use of Atezolizumab and Bevacizumab The risk of overlapping toxicities between atezolizumab and bevacizumab is anticipated to be minimal based on the known safety profile of each agent and available data from clinical studies. Nevertheless, the attribution and management of certa... | [] |
NCT04102098 | 5.2 | SAFETY PARAMETERS AND DEFINITIONS | 5.2 SAFETY PARAMETERS AND DEFINITIONS Safety assessments will consist of monitoring and recording adverse events, including serious adverse events and adverse events of special interest, performing protocol-specified safety laboratory assessments, measuring protocol-specified vital signs, and conducting other protocol-... | [] |
NCT04102098 | 5.2.1 | Adverse Events | 5.2.1 Adverse Events According to the ICH guideline for Good Clinical Practice, an adverse event is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. For patients in the active surveillance arm, an adverse event is any untoward m... | [] |
NCT04102098 | 5.2.2 | Serious Adverse Events (Immediately Reportable to the Sponsor) | 5.2.2 Serious Adverse Events (Immediately Reportable to the Sponsor) A serious adverse event is any adverse event that meets any of the following criteria: - Is fatal (i.e., the adverse event actually causes or leads to death) - Is life threatening (i.e., the adverse event, in the view of the investigator, places the p... | [] |
NCT04102098 | 5.2.3 | Adverse Events of Special Interest (Immediately Reportable to the Sponsor) | 5.2.3 Adverse Events of Special Interest (Immediately Reportable to the Sponsor) For patients receiving active treatment with atezolizumab plus bevacizumab, adverse events of special interest are required to be reported by the investigator to the Sponsor immediately (i.e., no more than 24 hours after learning of the ev... | [] |
NCT04102098 | 5.3 | METHODS AND TIMING FOR CAPTURING AND ASSESSING SAFETY PARAMETERS | 5.3 METHODS AND TIMING FOR CAPTURING AND ASSESSING SAFETY PARAMETERS The investigator is responsible for ensuring that all adverse events (see Section 5.2.1 for definition) are recorded on the Adverse Event eCRF and reported to the Sponsor in accordance with instructions provided in this section and in Sections 5.45.6.... | [] |
NCT04102098 | 5.3.1 | Adverse Event Reporting Period | 5.3.1 Adverse Event Reporting Period Investigators will seek information on adverse events at each patient contact (at clinic visits or using telemedicine). All adverse events, whether reported by the patient or noted by study personnel, will be recorded in the patient's medical record and on the Adverse Event eCRF. Af... | [] |
NCT04102098 | 5.3.2 | Eliciting Adverse Event Information | 5.3.2 Eliciting Adverse Event Information A consistent methodology of non-directive questioning should be adopted for eliciting adverse event information at all patient evaluation timepoints. Examples of non-directive questions include the following: "How have you felt since your last clinic visit?" "Have you had any n... | [] |
NCT04102098 | 5.3.3 | Assessment of Severity of Adverse Events | 5.3.3 Assessment of Severity of Adverse Events The adverse event severity grading scale for the NCI CTCAE (v5.0) will be used for assessing adverse event severity. Table 7 will be used for assessing severity for adverse events that are not specifically listed in the NCI CTCAE. Table 7 Adverse Event Severity Grading Sca... | [] |
NCT04102098 | 5.3.4 | Assessment of Causality of Adverse Events | 5.3.4 Assessment of Causality of Adverse Events Investigators should use their knowledge of the patient, the circumstances surrounding the event, and an evaluation of any potential alternative causes to determine whether an adverse event is considered to be related to study treatment, indicating "yes" or "no" according... | [
"Table 8 Causal Attribution Guidance"
] |
NCT04102098 | 5.3.5 | Procedures for Recording Adverse Events | 5.3.5 Procedures for Recording Adverse Events Investigators should use correct medical terminology/concepts when recording adverse events on the Adverse Event eCRF. Avoid colloquialisms and abbreviations. Only one adverse event term should be recorded in the event field on the Adverse Event eCRF. | [] |
NCT04102098 | 5.3.5.1 | Infusion-Related Reactions | 5.3.5.1 Infusion-Related Reactions Adverse events that occur during or within 24 hours after study treatment administration and are judged to be related to study treatment infusion should be captured as a diagnosis (e.g., "infusion-related reaction") on the Adverse Event eCRF. If possible, avoid ambiguous terms such as... | [] |
NCT04102098 | 5.3.5.2 | Diagnosis versus Signs and Symptoms | 5.3.5.2 Diagnosis versus Signs and Symptoms A diagnosis (if known) should be recorded on the Adverse Event eCRF rather than individual signs and symptoms (e.g., record only liver failure or hepatitis rather than jaundice, asterixis, and elevated transaminases). However, if a constellation of signs and/or symptoms canno... | [] |
NCT04102098 | 5.3.5.3 | Adverse Events That Are Secondary to Other Events | 5.3.5.3 Adverse Events That Are Secondary to Other Events In general, adverse events that are secondary to other events (e.g., cascade events or clinical sequelae) should be identified by their primary cause, with the exception of severe or serious secondary events. A medically significant secondary adverse event that ... | [] |
NCT04102098 | 5.3.5.4 | Persistent or Recurrent Adverse Events | 5.3.5.4 Persistent or Recurrent Adverse Events A persistent adverse event is one that extends continuously, without resolution, between patient evaluation timepoints. Such events should only be recorded once on the Adverse Event eCRF. The initial severity (intensity or grade) of the event will be recorded at the time t... | [] |
NCT04102098 | 5.3.5.5 | Abnormal Laboratory Values | 5.3.5.5 Abnormal Laboratory Values Not every laboratory abnormality qualifies as an adverse event. A laboratory test result must be reported as an adverse event if it meets any of the following criteria: - Is accompanied by clinical symptoms - Results in a change in study treatment (e.g., dosage modification, treatment... | [] |
NCT04102098 | 5.3.5.6 | Abnormal Vital Sign Values | 5.3.5.6 Abnormal Vital Sign Values Not every vital sign abnormality qualifies as an adverse event. A vital sign result must be reported as an adverse event if it meets any of the following criteria: - Is accompanied by clinical symptoms - Results in a change in study treatment (e.g., dosage modification, treatment inte... | [] |
NCT04102098 | 5.3.5.7 | Abnormal Liver Function Tests | 5.3.5.7 Abnormal Liver Function Tests The finding of an elevated ALT or AST (3 baseline value) in combination with either an elevated total bilirubin ( 2 ULN) or clinical jaundice in the absence of cholestasis or other causes of hyperbilirubinemia is considered to be an indicator of severe liver injury (as defined by H... | [] |
NCT04102098 | 5.3.5.8 | Deaths | 5.3.5.8 Deaths For this protocol, mortality is an efficacy endpoint. Deaths that occur during the protocol-specified adverse event reporting period (see Section 5.3.1) that are attributed by the investigator solely to progression of HCC should be recorded on the Death Attributed to Progressive Disease eCRF. All other d... | [] |
NCT04102098 | 5.3.5.9 | Preexisting Medical Conditions | 5.3.5.9 Preexisting Medical Conditions A preexisting medical condition is one that is present at the screening visit for this study. Such conditions should be recorded on the General Medical History and Baseline Conditions eCRF. A preexisting medical condition should be recorded as an adverse event only if the frequenc... | [] |
NCT04102098 | 5.3.5.10 | Lack of Efficacy or Worsening of Hepatocellular Carcinoma | 5.3.5.10 Lack of Efficacy or Worsening of Hepatocellular Carcinoma Events that are clearly consistent with the expected pattern of disease recurrence should not be recorded as adverse events. These data will be captured as efficacy assessment data only. However, in situations in which there is no confirmation of diseas... | [] |
NCT04102098 | 5.3.5.11 | Hospitalization or Prolonged Hospitalization | 5.3.5.11 Hospitalization or Prolonged Hospitalization Any adverse event that results in hospitalization (i.e., inpatient admission to a hospital) or prolonged hospitalization should be documented and reported as a serious adverse event (per the definition of serious adverse event in Section 5.2.2), except as outlined b... | [] |
NCT04102098 | 5.3.5.12 | Cases of Accidental Overdose or Medication Error | 5.3.5.12 Cases of Accidental Overdose or Medication Error Accidental overdose and medication error (hereafter referred to as "special situations") are defined as follows: - Accidental overdose: accidental administration of a drug in a quantity that is higher than the assigned dose - Medication error: accidental deviati... | [] |
NCT04102098 | 5.3.5.13 | Patient-Reported Outcome Data | 5.3.5.13 Patient-Reported Outcome Data Adverse event reports will not be derived from PRO data by the Sponsor. Sites are not expected to review the PRO data for adverse events. | [] |
NCT04102098 | 5.4 | IMMEDIATE REPORTING REQUIREMENTS FROM INVESTIGATOR TO SPONSOR | 5.4 IMMEDIATE REPORTING REQUIREMENTS FROM INVESTIGATOR TO SPONSOR Certain events require immediate reporting to allow the Sponsor to take appropriate measures to address potential new risks in a clinical trial. The investigator must report such events to the Sponsor immediately; under no circumstances should reporting ... | [] |
NCT04102098 | 5.4.1 | Emergency Medical Contacts | 5.4.1 Emergency Medical Contacts To ensure the safety of study participants, access to the Medical Monitors is available 24 hours per day, 7 days per week. Details will be provided separately. The Emergency Medical Call Center will also be available 24 hours per day, 7 days per week. The Emergency Medical Call Center w... | [] |
NCT04102098 | 5.4.2 | Reporting Requirements for Serious Adverse Events and Adverse Events of Special Interest | 5.4.2 Reporting Requirements for Serious Adverse Events and Adverse Events of Special Interest | [] |
NCT04102098 | 5.4.2.1 | Events That Occur prior to Study Treatment Initiation | 5.4.2.1 Events That Occur prior to Study Treatment Initiation After informed consent has been obtained but prior to initiation of study treatment or surveillance on Day 1 of Cycle 1, only serious adverse events caused by a protocol-mandated intervention should be reported. The paper Clinical Trial Adverse Event/Special... | [] |
NCT04102098 | 5.4.2.2 | Events That Occur after Study Treatment Initiation | 5.4.2.2 Events That Occur after Study Treatment Initiation After initiation of study treatment or surveillance on Day 1 of Cycle 1, serious adverse events and adverse events of special interest will be reported until 90 days after the final cycle (i.e., final cycle of treatment or surveillance) or until initiation of n... | [] |
NCT04102098 | 5.4.3 | Reporting Requirements for Pregnancies | 5.4.3 Reporting Requirements for Pregnancies | [] |
NCT04102098 | 5.4.3.1 | Pregnancies in Female Patients | 5.4.3.1 Pregnancies in Female Patients Female patients of childbearing potential will be instructed through the Informed Consent Form to immediately inform the investigator if they become pregnant during the study or within 5 months after the final dose of atezolizumab or 6 months after the final dose of bevacizumab. A... | [] |
NCT04102098 | 5.4.3.2 | Pregnancies in Female Partners of Male Patients | 5.4.3.2 Pregnancies in Female Partners of Male Patients Male patients will be instructed through the Informed Consent Form to immediately inform the investigator if their partner becomes pregnant during the study or within 6 months after the final dose of bevacizumab. The investigator should report the pregnancy on the... | [] |
NCT04102098 | 5.4.3.3 | Abortions | 5.4.3.3 Abortions A spontaneous abortion should be classified as a serious adverse event (as the Sponsor considers abortions to be medically significant), recorded on the Adverse Event eCRF, and reported to the Sponsor immediately (i.e., no more than 24 hours after learning of the event; see Section 5.4.2). If a therap... | [] |
NCT04102098 | 5.4.3.4 | Congenital Anomalies/Birth Defects | 5.4.3.4 Congenital Anomalies/Birth Defects Any congenital anomaly/birth defect in a child born to a female patient exposed to study treatment or the female partner of a male patient exposed to study treatment should be classified as a serious adverse event, recorded on the Adverse Event eCRF, and reported to the Sponso... | [] |
NCT04102098 | 5.5 | FOLLOW-UP OF PATIENTS AFTER ADVERSE EVENTS | 5.5 FOLLOW-UP OF PATIENTS AFTER ADVERSE EVENTS | [] |
NCT04102098 | 5.5.1 | Investigator Follow-Up | 5.5.1 Investigator Follow-Up The investigator should follow each adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the patient is lost to follow-up, or the patient withdraws consent. Every effort should be made to follow all serious adverse even... | [] |
NCT04102098 | 5.5.2 | Sponsor Follow-Up | 5.5.2 Sponsor Follow-Up For serious adverse events, adverse events of special interest, and pregnancies, the Sponsor or a designee may follow up by telephone, fax, email, and/or a monitoring visit to obtain additional case details and outcome information (e.g., from hospital discharge summaries, consultant reports, aut... | [] |
NCT04102098 | 5.6 | ADVERSE EVENTS THAT OCCUR AFTER THE ADVERSE EVENT REPORTING PERIOD | 5.6 ADVERSE EVENTS THAT OCCUR AFTER THE ADVERSE EVENT REPORTING PERIOD After the end of the reporting period for serious adverse events and adverse events of special interest (defined as 90 days after the final cycle or until initiation of new systemic anti-cancer therapy, whichever occurs first), all deaths, regardles... | [] |
NCT04102098 | 5.7 | EXPEDITED REPORTING TO HEALTH AUTHORITIES, INVESTIGATORS, INSTITUTIONAL REVIEW BOARDS, AND ETHICS COMMITTEES | 5.7 EXPEDITED REPORTING TO HEALTH AUTHORITIES, INVESTIGATORS, INSTITUTIONAL REVIEW BOARDS, AND ETHICS COMMITTEES The Sponsor will promptly evaluate all serious adverse events and adverse events of special interest against cumulative product experience to identify and expeditiously communicate possible new safety findin... | [] |
NCT04102098 | 6 | STATISTICAL CONSIDERATIONS AND ANALYSIS PLAN | 6. STATISTICAL CONSIDERATIONS AND ANALYSIS PLAN The statistical considerations and analysis plan are summarized below. Further details will be provided in the Statistical Analysis Plan (SAP) as part of the Data Analysis Plan. The global population will include all patients enrolled during the global enrollment phase (i... | [] |
NCT04102098 | 6.1 | DETERMINATION OF SAMPLE SIZE | 6.1 DETERMINATION OF SAMPLE SIZE A total of approximately 662 patients will be randomized in the global enrollment phase of this study using a 1:1 randomization ratio to allocate patients to either the atezolizumab plus bevacizumab arm (Arm A) or the active surveillance arm (Arm B). The primary efficacy endpoint for th... | [] |
NCT04102098 | 6.2 | SUMMARIES OF CONDUCT OF STUDY | 6.2 SUMMARIES OF CONDUCT OF STUDY Study enrollment, study treatment administration, reasons for discontinuation from the study treatment, and reasons for study discontinuation will be summarized by study arm for all randomized patients (the ITT population). Major protocol deviations, including major deviations with reg... | [] |
NCT04102098 | 6.3 | SUMMARIES OF TREATMENT GROUP COMPARABILITY | 6.3 SUMMARIES OF TREATMENT GROUP COMPARABILITY Demographic characteristics such as age, sex, race/ethnicity, and baseline disease characteristics (e.g., ECOG Performance Status) will be summarized by study arm for the ITT population. Descriptive statistics (mean, median, standard deviation, and range) will be presented... | [] |
NCT04102098 | 6.4 | EFFICACY ANALYSES | 6.4 EFFICACY ANALYSES The analyses of RFS, OS, time to recurrence (TTR), and time to extrahepatic spread (EHS) or macrovascular invasion will be performed on the basis of all randomized patients (the ITT population), with patients grouped according to the treatment assigned at randomization, regardless of whether they ... | [] |
NCT04102098 | 6.4.1 | Primary Efficacy Endpoint | 6.4.1 Primary Efficacy Endpoint The primary efficacy endpoint is IRF-assessed RFS, defined as the time from randomization to the first documented occurrence of intrahepatic or extrahepatic HCC, or death from any cause (whichever occurs first). Patients who have not experienced disease recurrence or death at the time of... | [] |
NCT04102098 | 6.4.2 | Secondary Efficacy Endpoints | 6.4.2 Secondary Efficacy Endpoints The secondary efficacy endpoints are OS, investigator-assessed RFS, investigator-assessed and IRF-assessed TTR, , investigator- and IRF-assessed RFS rate at 24 months and 36 months, OS rate at 24 months and 36 months, investigator-assessed time to EHS or macrovascular invasion, and in... | [] |
NCT04102098 | 6.4.2.1 | Overall Survival | 6.4.2.1 Overall Survival The OS will be defined as the time from randomization to death from any cause. Patients who are alive at the time of the analysis will be censored at the last date the patient was known to be alive. Patients with no postbaseline information will be censored at the date of randomization. The ana... | [] |
NCT04102098 | 6.4.2.2 | InvestigatorAssessed Recurrence Free Survival | 6.4.2.2 InvestigatorAssessed Recurrence Free Survival The analysis methods for investigator-assessed RFS are analogous to those described for IRF-assessed RFS (see Section 6.4.1). | [] |
NCT04102098 | 6.4.2.3 | Time to Recurrence | 6.4.2.3 Time to Recurrence The TTR is defined as the time from randomization to first documented occurrence of intrahepatic or extrahepatic HCC. Patients who have not experienced disease recurrence at the time of the analysis will be censored at the date of the last assessment for HCC occurrence. Patients with no postb... | [] |
NCT04102098 | 6.4.2.4 | IRF-Assessed and Investigator-Assessed RFS at 24-Month and 36-Month Landmark Analysis | 6.4.2.4 IRF-Assessed and Investigator-Assessed RFS at 24-Month and 36-Month Landmark Analysis The IRF- and investigator-assessed RFS rates at 24 months and 36 months will be estimated for each study arm through use of the Kaplan-Meier method, with 95% CIs calculated through use of Greenwood's formula. | [] |
NCT04102098 | 6.4.2.5 | Overall Survival 24-Month and 36-Month Landmark Analysis | 6.4.2.5 Overall Survival 24-Month and 36-Month Landmark Analysis The OS rates at 24 months and 36 months will be estimated for each study arm through use of the Kaplan-Meier method, with 95% CIs calculated through use of Greenwood's formula. | [] |
NCT04102098 | 6.4.2.6 | Time to Extrahepatic Spread or Macrovascular Invasion | 6.4.2.6 Time to Extrahepatic Spread or Macrovascular Invasion Time to EHS or macrovascular invasion is defined as the time from randomization to the first appearance of EHS or macrovascular invasion. The analysis of time to EHS or macrovascular invasion will be conducted for the study period prior to crossover. Events ... | [] |
NCT04102098 | 6.4.2.7 | Recurrence-Free Survival among Patients with PD-L1High Tumors | 6.4.2.7 Recurrence-Free Survival among Patients with PD-L1High Tumors The RFS among patients in the PD-L1high subgroup is defined in an analogous manner to the primary endpoint and will be analyzed through use of same methods described for the primary endpoint (see Section 6.4.1). The analysis of RFS in the PD-L1high s... | [] |
NCT04102098 | 6.4.3 | Exploratory Efficacy Endpoints | 6.4.3 Exploratory Efficacy Endpoints
Exploratory Overall Survival Analyses The OS among patients in the PD-L1high subgroup is defined in an analogous manner to OS in the ITT population and will be analyzed through use of the same methods described for OS in the ITT population (see Section 6.4.2.1). The cutoff to defin... | [
"Exploratory Overall Survival Analyses",
"Exploratory Patient-Reported Outcome Analyses",
"Exploratory Efficacy Analyses in Arm B Patients Who Cross Over to Treatment with Atezolizumab Plus Bevacizumab"
] |
NCT04102098 | 6.5 | SAFETY ANALYSES | 6.5 SAFETY ANALYSES The safety analysis population will consist of all patients randomized to Arm A who received at least one full or partial dose of study treatment (atezolizumab and/or bevacizumab) and all patients randomized to Arm B who underwent at least one safety assessment. Safety analyses will be conducted sep... | [] |
NCT04102098 | 6.6 | PHARMACOKINETIC ANALYSES | 6.6 PHARMACOKINETIC ANALYSES The PK analysis population will consist of all patients with at least one PK assessment. Serum concentrations of atezolizumab will be reported as individual values and summarized (geometric mean and geometric mean coefficient of variation) by cycle, when appropriate and as data allow. Indiv... | [] |
NCT04102098 | 6.7 | IMMUNOGENICITY ANALYSES | 6.7 IMMUNOGENICITY ANALYSES The immunogenicity analysis population will consist of all patients with at least one ADA assessment. Patients will be grouped according to treatment received or, if no treatment is received prior to study discontinuation, according to treatment assigned. The numbers and proportions of ADA-p... | [] |
NCT04102098 | 6.8 | BIOMARKER ANALYSES | 6.8 BIOMARKER ANALYSES Although no formal statistical analysis of exploratory biomarkers will be performed, biomarker data may be analyzed in the context of this study and in aggregate with data from other studies. | [] |
NCT04102098 | 6.9 | HEALTH UTILITY ANALYSES | 6.9 HEALTH UTILITY ANALYSES Health utility data from the EQ-5D-5L will be evaluated in pharmacoeconomic models. The results from the health economic data analyses will be reported separately from the clinical study report. | [] |
NCT04102098 | 6.10 | INTERIM ANALYSES | 6.10 INTERIM ANALYSES | [] |
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