So More

Institut Jules Bordet

rue Héger Bordet 1, Bruxelles, Belgium, 1000

Dr. Alain Hendlisz, Institut Jules Bordet, 32 025413196, alain.hendlisz@bordet.be

Dr. Alain Hendlisz, Institut Jules Bordet, 32 025413196, alain.hendlisz@bordet.be

No

No

No

Final

05 Jan 2016

Yes

04 Dec 2013

Yes

20 Dec 2016

No

a) To obtain a preliminary assessment about the activity of the combination by estimating overall survival of the study population at a fixed time point (6 months) b) To compare as an exploratory analysis the overall survival of metabolic responders versus non-responders.

Some of the eligibility criteria that the subjects had to meet to be entered in the trial were chosen in order to minimize the risk of severe adverse events. In addition, the protocol planned rules for treatment modifications in case of the occurrence of specific adverse events. All subjects were free to withdraw from the clinical trial at any time for any reason given and the study was conducted in agreement with the declaration of Helsinki. It was controlled that the patients received before inclusion in the trial all standard medications that could be of benefit for them.

18 Feb 2011

No

No

Belgium: 97

97

97

0

0

0

0

0

0

63

34

0

Overall trial (overall period)

Not applicable

sorafenib

Film-coated tablet

Oral use

200 mg in the morning, 400 mg in the evening escalation to 400 mg twice daily continuous; dosing 21 days (3 weeks)

capecitabine

Film-coated tablet

Oral use

850 mg/m2 twice daily; days 1-14; weeks 1-2

Overall trial

Investigational medicinal products

Metabolic Response

Patients were classified according to the lesional distribution of mR; Class 1: no metabolic unresponsive lesion; Class 2: minority of unresponsive lesion among whole body target tumour load; Class 3: majority of whole body target tumour load does not respond; Class 4: all target lesions are non-responding, or, presence of progressive lesions [progression defined as >25% increase of FDG uptake on second PET, or appearance of a new lesion]. MR data were available for 79 patients: 37 (46.8%) were classified as class I; 14 (17.7%) as class II; 11 (13.9%) as class III; and 17 (21.5%) as class IV. Within Class IV, 8 patients (10%) showed early metabolic disease progression.

Survival data

This subject analysis set is used to assess OS and PFS. Patients were followed until objective disease progression and every 3 months thereafter for survival assessment.

Metabolic Response Class I

Patients with absence of any metabolically non-responding lesion

Metabolic Response Class II-III-IV

Patients with heterogeneous responses (minor part of whole body tumour load shows a non-response or major part of whole body target tumour load does not respond) and patients with all target lesions are non-responding, or presence of a progressive lesion.

Overall survival is defined as the time from start of therapy until death

Primary

start of therapy until death

The multivariate analysis was performed using Cox’s proportional hazard model. Variables with a univariate P-value < 0.20 were considered as possible predictors in the multivariate model. We performed stepwise forward selection of variables, i.e. forward selection but at each step variables already in the model could be dropped if their associated p-value became >0.05. To verify the final model, also backward selection of variables was performed on all variables with univariate p-value<0.20

Metabolic Response Class I v Metabolic Response Class II-III-IV

79

Pre-specified

2-sided

Progression free survival is defined as the interval between the start of treatment and the earliest date of disease progression or death due to any cause. Assessments of progression were made by investigator.

Secondary

start of therapy until disease progression

The multivariate analysis was performed using Cox’s proportional hazard model. Variables with a univariate P-value < 0.20 were considered as possible predictors in the multivariate model. We performed stepwise forward selection of variables, i.e. forward selection but at each step variables already in the model could be dropped if their associated p-value became >0.05. To verify the final model, also backward selection of variables was performed on all variables with univariate p-value<0.20

Metabolic Response Class II-III-IV v Metabolic Response Class I

79

Pre-specified

2-sided

Secondary

6 months after registration

Overall response is the number of participants who had a best outcome of a complete response (CR, all detectable tumour disappeared) or a partial response (PR, a >= 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum) per response evaluation criteria in solid tumours (RECIST v1.1) at some point during the study. Progressive disease (PD), a >= 20% increase in target lesions. RECIST radiological response was assessed locally every two cycles (6 weeks). Patients were followed until objective disease progression and every 3 months thereafter for survival assessment.

Secondary

baseline until either response or progression

Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first administration of study treatments until 30 days after the last dose of study treatments.

88 subjects were exposed to the investigational medicinal products.

19.1

All serious adverse events