Clinical Study Synopsis

Transcription

1 Clinical Study Synopsis This Clinical Study Synopsis is provided for patients and healthcare professionals to increase the transparency of Bayer's clinical research. This document is not intended to replace the advice of a healthcare professional and should not be considered as a recommendation. Patients should always seek medical advice before making any decisions on their. Healthcare Professionals should always refer to the specific labelling information approved for the patient's country or region. Data in this document or on the related website should not be considered as prescribing advice. The study listed may include approved and non-approved formulations or regimens. Data may differ from published or presented data and are a reflection of the limited information provided here. The results from a single trial need to be considered in the context of the totality of the available clinical research results for a drug. The results from a single study may not reflect the overall results for a drug. The following information is the property of Bayer HealthCare. Reproduction of all or part of this report is strictly prohibited without prior written permission from Bayer HealthCare. Commercial use of the information is only possible with the written permission of the proprietor and is subject to a license fee. Please note that the General Conditions of Use and the Privacy Statement of bayerhealthcare.com apply to the contents of this file.

2 14 th Nov Page: 1 of 8 Date of study report: 24th July 2014 Study title: NEXTAR - NEXavar as first TARgeted for patients with advanced Renal Cell Carcinoma Sponsor s study (NX1111) number: NCT number: NCT EudraCT number: Not applicable Sponsor: Bayer HealthCare Clinical phase: Non-Interventional Post Authorization Study Study objectives: Primary Objective: Determination of the duration of Nexavar when Nexavar was used as first targeted for patients with advanced RCC (Renal Cell Carcinoma) under current practice conditions in both oncological as well as urological clinics and practices. Secondary objectives: Health related quality of life (HRQoL) Progression free survival (PFS) Time to progression (TTP) Time to failure (progression, or discontinuation due to toxicity) Overall Survival (OS) Tumor status at different visits General subjective rating of efficacy of Nexavar from the treating investigator Incidence of -emergent adverse events (TEAE) Overall tolerability assessment Addressing possible prognostic factors Test drug: Sorafenib (Nexavar, BAY ) Name of active Sorafenib ingredient(s): Dose: According to the recommendations written in the local product information Route of Oral use administration: Duration of : According to the recommendations written in the local Summary of medicinal Product Characteristics (SmPC): decision is made at the discretion of the attending investigator

3 14 th Nov Page: 2 of 8 Reference drug: Not applicable Indication: Renal Cell Carcinoma Inclusion criteria: Diagnosis and main criteria for inclusion: Patients with a diagnosis of advanced RCC for whom the decision has been taken by the investigator to prescribe Nexavar Patients who failed cytokine therapy or who are not suitable for cytokines for whom Nexavar was the first targeted drug Written informed consent Exclusion criteria: Prior targeted therapy for RCC Study design: Contraindications of Nexavar described in the Summary of Product Characteristics This prospective, non-interventional, multi-center study documented observational data on patients under routine of advanced renal cell carcinoma with Nexavar. The observation period for each patient covered the period with Nexavar until the end of Nexavar. For each patient, the investigator or a delegate collected data as defined in the case report form at an initial visit, follow-up visits and final visit. Methodology: The investigator collected historic data (demographic and clinical characteristics) from medical records if available, or else by interviewing the patient. Likewise, the investigator collected related data during initial visit and follow-up visits. At initial visit, at each follow-up visit and at final visit the investigator asked the patient to fill out a QoL-questionnaire (FKSI-10). The observation period covered the whole with Nexavar. Followup visits were documented every 2 to 3 months (depending on the individual visit schedule of the patient). At each follow-up time point, the patient s condition and a assessment were documented. The final data collection (last visit) was at discontinuation of therapy or at end of study (whatever was earlier). At this final observation point, the patient s condition and a assessment were documented. At the end of the study all investigators were asked regarding the current and status of their patients. The investigator or a delegate used an electronic case report form (ecrf) to document the study data. The data were recorded in an electronic data capture (EDC) system. Study center(s): 60 centers in Germany Publication(s) based on None at the time of report creation the study (references):

4 14 th Nov Page: 3 of 8 Study period: Study Start Date: 16 Jul 2012 Study Completion Date: 31-Mar-2014 Early termination: Data cutoff date: 31st December 2013, due to lack of recruitment. Number of subjects: Planned: 400 Criteria for evaluation Analyzed: 20 Efficacy: [Primary]: Duration of Nexavar [Secondary]: Health related quality of life (HRQoL) Progression-free survival (PFS) Time to progression (TTP) Time to failure Overall Survival (OS) Tumor status General subjective rating of efficacy of Nexavar from the treating investigator Addressing possible prognostic factors Safety: Incidence of Treatment-emergent Adverse Events (TEAE) Overall tolerability assessment

5 14 th Nov Page: 4 of 8 Statistical methods: Substantial protocol changes: Statistical analyses were primarily of explorative and descriptive nature. All issues concerning patient validity, data consistency checks, permissible data modifications were described in detail in the Data Management Plan. All statistical issues including calculated variables and proposed format and content of tables were detailed in the Statistical Analysis Plan. Patients who took at least one dose of Nexavar and had sufficient information whether they had an adverse event or not (i.e. who had a followup visit page and/or an AE page) were valid for safety analysis. Patients who took at least one dose of Nexavar and had any information regarding efficacy of sorafenib were valid for intent-to-treat efficacy analysis. Demographic data, baseline characteristics, diagnosis and prior of RCC and concomitant diseases were described with summary statistics such as mean, SD, minimum, 1, 5, 25, 75, 95, 99 percentiles, median, maximum for continuous variables, and category counts and frequencies (percentages) for categorical variables. Concomitant diseases on the case report form correspond to MedDRA terms. Concomitant medication was listed. Adverse events were summarized using the MedDRA and the CTCAE coding system. Event rates for single adverse events were calculated based on the total number of patients valid for safety. Adverse events were categorized according to relation, seriousness, CTCAE grade (version 4.03), discontinuation of therapy, action taken and outcome. Special attention was paid to serious adverse events. Tolerability was listed. Protocol Amendments were not performed. The study was conducted according the Protocol version 1.1 dated 2011-OCT-24. Subject disposition and baseline All patients had a first targeted and had given their informed consent. Their median age at informed consent was 74 years, 57.9% of them were male and nearly all patients were white (94.7%). Furthermore, the median height was 166 cm, the median weight at initial diagnosis 75 kg and the median BMI 25.5 kg/m². The tumor stage at initial diagnosis was in most cases stage III (31.6%) or stage IV (26.3%) and the tumor grade G2 (moderately well differentiated) (52.6%). Clear cell carcinoma was the only documented tumor subtype. Regarding the prior s, 14 patients (73.7%) had a nephrectomy for primary tumor, 2 patients (10.5%) had a cytokine therapy for RCC and one patient (5.3%) other systemic anti-cancer therapies for RCC. Specifying the cytokine therapies, interferon alpha and interleukin 2 were administered in both cases. The best response of the last before Nexavar was stable disease in 2 patients and progressive disease in one patient. 57.9% of the patients were unsuitable for cytokine therapy, mostly because they were older than 65 years (90.9%). 31.6% of the patients were suitable for therapy but did not get one. Beyond, the only other systemic anti-cancer for RCC was Nexavar. Hypertension was the most often documented concomitant disease and occurred in 73.7% of the patients.

6 14 th Nov Page: 5 of 8 Efficacy evaluation 11 patients (57.9%) discontinued the therapy permanently. The duration of Nexavar therapy ranged from 31 days to 510 days for the 11 patients who discontinued the therapy permanently and at least from 223 days to 485 days for the patients with an ongoing therapy. The health related quality of life was measured by FKSI-10 as detailed in Listing 1 (see below). Six patients showed a progression, which occurred between 71 to 241 days after last. Three patients died, one without progression. The best response was mainly stable disease (79%, 15 patients), followed by partial response and progressive disease (10.5%, 2 patients, respectively). The general subjective rating of efficacy of Nexavar by the treating investigator was good or very good in 79% of the cases (15 patients); only 10.5% (2 patients) were rated as insufficient. The tolerability of the was mostly good or very good (42.1%, 8 patients). Only in one case it was regarded as poor. During Nexavar therapy only one dose change was documented, which was not due to AE, whereas the 5 interruptions being documented were due to the occurrence of AE. The therapy was discontinued in 11 cases. Not all objectives were evaluated due to low recruitment. Listing 1: Health related quality of life HRQoL (FKSI-10) Patient No. Visit Days since start of FKSI- 10 GP1: I a lack of energy GP5: I am bothered by side effects of GP4: I C2: I am losing weight BP1: I bone HI7: I feel fatigued GF3: I am able to enjoy life B1: I been short of breath GE6: I worry that my condition will get worse C6: I a good appetite Initial visit Follow-up Follow-up Follow-up visit Final visit Initial visit Follow-up Final visit Follow-up Follow-up Follow-up Follow-up visit Final visit Initial visit visit

7 14 th Nov Page: 6 of 8 Patient No. Visit visit5 visit6 visit7 visit8 0 Days since start of FKSI- 10 GP1: I a lack of energy GP5: I am bothered by side effects of GP4: I C2: I am losing weight BP1: I bone HI7: I feel fatigued GF3: I am able to enjoy life B1: I been short of breath GE6: I worry that my condition will get worse C6: I a good appetite Final visit Initial visit visit4 visit5 visit6 visit Final visit Initial visit Follow-up Follow-up Initial visit Final visit Initial visit Follow-up Follow-up Follow-up Follow-up visit Follow-up visit Initial visit Follow-up Follow-up Follow-up Final visit Initial visit

8 14 th Nov Page: 7 of 8 Patient No. Visit Follow-up Days since start of FKSI- 10 GP1: I a lack of energy GP5: I am bothered by side effects of GP4: I C2: I am losing weight BP1: I bone HI7: I feel fatigued GF3: I am able to enjoy life B1: I been short of breath GE6: I worry that my condition will get worse C6: I a good appetite Initial visit Follow-up Follow-up Follow-up Final visit Initial visit Follow-up Follow-up Follow-up Final visit Initial visit Follow-up Follow-up Unknown Follow-up Follow-up visit Final visit Initial visit Unknown Follow-up Follow-up Initial visit Follow-up Unknown Safety evaluation A total of 64 adverse events occurred in 12 patients. The most common AE was diarrhea (36.8%, 7 patients), followed by palmar-plantar erythrodysaesthesia syndrome (PPES) (21.1%, 4 patients) and fatigue and (15.8%, 3 patients). Half of the AE (32 events) were of grade 1, 15 events (23.4%) of grade 2, 13 events (20.3%) of grade 3, and only 4 events (6.3%) were of grade 5. Furthermore, 17 adverse events (26.6%) were classified as serious and occurred in 7 patients. Additionally, 27 of the adverse events (42.2%) occurring in 8 patients were documented to be in causal relationship with

9 14 th Nov Page: 8 of 8 Nexavar. The most common were diarrhea (31.6%, 6 patients), followed by palmar-plantar erythrodysaesthesia syndrome (21.1%, 4 patients), alopecia (2 patients), and nausea (2 patients). 17 of the 64 adverse events were classified as serious (26.6%). 4 serious adverse events turned out to be drug-related (acute myocardial infarction and jugular vein thrombosis occurring in one patient, intracranial hemorrhage and convulsion were observed in another patient). In addition, three patients (15.8%) experienced a serious adverse event with fatal outcome. One patient died due to intracranial hemorrhage and convulsion, two further patients died due to tumor progression. Overall conclusions The aim of this NIS was the evaluation of feasibility, efficacy and tolerability of Nexavar of patients with advanced or metastatic Renal Cell Carcinoma (RCC) in daily routine practice. Due to premature termination of the study, only few data of 19 evaluable patients are available. Hence, the above mentioned endpoints could not be addressed adequately. As far as conclusion can be drawn from this study, sorafenib at doses of routine practice result in acceptable and well tolerated salvage for patients with metastatic/advanced RCC, who failed or were not suitable for prior cytokine therapy and for whom Nexavar constituted first targeted therapy. The adverse events reported in this study are in line with the known adverse event profile of former studies and as specified in the SmPC of Nexavar. The only exception was 1 serious adverse event jugular vein thrombosis, that was attributed to be drug-related, but is not described in the SmPC. Besides, no new and unexpected safety findings were noted. The results confirm the antitumor activity and good safety profile of sorafenib in the of metastatic/advanced RCC, and do support the use of sorafenib as a first targeted therapy in this setting.

10 Appendix to Clinical Study Synopsis Product Identification Information Product Type US Brand/Trade Name(s) Brand/Trade Name(s) ex-us Generic Name Main Product Company Code Other Company Code(s) Chemical Description Other Product Aliases Drug Nexavar Nexavar Sorafenib BAY BAY (1) 2-Pyridinecarboxamide, 4-[4-[[[[4-chloro- 3trifluoromethyl)phenyl]amino]carbonyl]amino]phenoxy]-Nmethyl-(2) 4-(4-{3.[4-chloro-3- (trifluoromethyl)phenyl]ureido}phenoxy)-n2- methylpyridine-2-carboxamide Sorafenib tosylate Date of last Update/Change: 28 Apr 2012