Secondary endpoints. Secondary safety endpoints include: · change from baseline in LV dimensions (end-systolic volume index, end-diastolic volume index, left ventricular mass) · change from baseline in regional (infarct related) and global wall motion score · change from baseline in ejection fraction · cardiac rupture · NT-proBNP
4.1 Summary of study design
Secondary endpoints.
1) Pathological and histologicalevaluation of the acute thermal effect, produced by the ANET device, on targeted pulmonary nodule/tumor and surrounding tissue to determine if the observed zone of ablation is localized and consistent with the predicted zone of ablation.
2) Characterize any effects on surrounding tissue outside the zone of predicted ablation.
Secondary endpoints. The secondary endpoints of this clinical trial include:
1. A reduction in spontaneous axillary sweat production assessed by gravimetric method at all time points following completion of study treatment(s), as measured by a 50% reduction or more compared to baseline.
a. Gravimetric method is performed by drying the surface of the skin, then applying a pre-weighed filter paper to the axilla for a period of time measured by a stopwatch. The paper is then weighed and the rate of sweat production is calculated in mg/min.
2. HDSS score reduction from a 3 or 4 to a 1 or 2 at 90 days post treatment #2.
3. Starch iodine test to assess area of efficacy.
a. Starch Iodine test is performed by applying an iodine solution to the sweaty area. After it dries, starch is sprinkled on the area. The starch-iodine combination turns a dark blue color wherever excess sweat is present. Digital images of the starch iodine test will be obtained.
Secondary endpoints. To describe the resilience scores at baseline and during and after the targeted interventions and to compare the results to a control population of the former BOUNCE prospective pilot study without interventions. The information about the usability of the tool and targeting the interventions will be collected from the trial nurse using the tool.
Secondary endpoints. The secondary endpoints of the study are to compare the following between the two treatment groups: • Safety as measured by adverse events, including clinically significant changes in physical examination, peripheral blood hematology, serum chemistry, urinalysis, and ECG. • The OS of patients with recurrent or metastatic SCCHN. • The ORR, DOBR, DCR, and DDC of patients with recurrent or metastatic SCCHN using irRECIST evaluated by independent radiology review.
Secondary endpoints. ● Objective response rate (OXX) as defined by RECIST v1.1 (Appendix B) Patients who respond to treatment and die without PD (including death from study disease), duration of response will be censored at the date of the last objective progression-free disease assessment. For responding patients not known to have died as of the data cut-off date and who do not have PD, duration of response will be censored at the last progression-free assessment date. For responding patients who receive subsequent anticancer therapy (after discontinuation from all study treatment excluding PCI) prior to disease progression, duration of response will be censored at the date of last progression-free assessment prior to the initiation of post discontinuation anticancer therapy ● Duration of overall response as defined by RECIST v1.1 (Appendix B) ● Safety and Adverse events by assessed by CTCAE version 5.0 ● Progression-free survival (PFS) as defined by RECIST v1.1 (Appendix B) ● Overall survival, which is defined as the time from the date of study enrollment to the date of death from any cause. For patients who are still alive as of the data cutoff date, OS time will be censored on the date of the patient’s last contact (last contact for patients in post discontinuation is last known alive date in mortality status).
Secondary endpoints. [***] from [***] will be [***] the [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***]
Secondary endpoints. PHARMACOKINETIC ENDPOINTS
i. For TID dosing, samples will be obtained before Dose 7 and 0.5, 1, 2, 4, and 6 hours after Dose 7. This serial PK sampling may be done for Dose 7, 8, or 9, based on site/patient convenience
ii. For BID dosing, samples will be obtained before Dose 5 and 0.5, 1, 2, 4, 6, and 8 hours after Dose 5. This serial PK sampling may be done for Dose 5, 6, or 7, based on site/patient convenience For blood samples (both TID and BID dosing), a ±10-minute window for time points ≤4 hours; ±15 minute for time points between 4 and 24 hours o At any early study discontinuation visits. The timing of these PK samples relative to the last 2 (most recent) doses will be recorded • Noncompartmental analysis will be performed for the following plasma PK parameters, when applicable and if data permit. Other PK parameters may also be calculated. PK parameters, where applicable, will be calculated based on actual times: o AUClast (area under the plasma concentration versus time curve from time 0 to the last quantifiable concentration) o AUCtau (area under the plasma concentration versus time curve over the dosing interval) o AUCinf (area under the plasma concentration versus time curve from time 0 to extrapolated to infinity) o Cmax o Tmax o t1/2z (apparent terminal elimination half-life) o CL/F for AT-281 only (apparent oral clearance) o Vz/F for AT-281 only (apparent volume of distribution)
Secondary endpoints. SAFETY ENDPOINTS
Secondary endpoints. IRRC-assessed XXX and PFS, and OS, in any-risk subjects with previously untreated RCC. Incidence of AEs in all treated subjects with previously untreated advanced or metastatic RCC Exploratory Endpoints: Overall safety and tolerability of NIVO+IPI versus sunitinib. IRRC-assessed XXX and PFS, and OS in favourable-risk subjects with previously untreated advanced or metastatic RCC. Explore potential predictive biomarkers of clinical response by analyzing tumor specimens and blood samples for proteins and genes involved in regulating immune responses. Evaluate HRQoL as assessed by FACT-G. Assess disease related symptoms in each arm based on NCCN FKSI-19. Assess changes in global health status based on EuroQol’s EQ-5D.
