Trial Outcomes & Findings for Comparison of In-House Methods and Cobas BRAF V600 Mutation Assay in Melanoma Tumor Samples (NCT NCT01744860)

NCT ID: NCT01744860

Last Updated: 2016-03-28

Results Overview

BRAF V600 mutation status was determined by INCa molecular laboratories "in-house" methods and Cobas 4800 BRAF V600 mutation test. Samples were analysed as V600 mutation, No V600 mutation and Non evaluable. Additionally, the type of V600 mutation (E, K, R, D, E2, other V600 mutation, not specified) was also evaluated only by INCa molecular laboratory "in-house" method.

• Recruitment status: COMPLETED
• Target enrollment: 420 participants
• Primary outcome timeframe: Up to 6 months
• Results posted on: 2016-03-28

Participant Flow

The study was conducted from 12 December 2012 to 03 April 2013 which evaluated 420 samples for detection of BRAF V600 mutation in France laboratories.

A total 420 melanoma tumor samples were analysed in 12 platform laboratories in France. The paraffin-embedded tumour samples were taken from biopsy or surgical specimen from the internal or external pathology laboratory.

Participant milestones

Measure	Melanoma Tumor Sample With BRAF V600 Mutation BRAF V600 mutations were analysed in melanoma tumor samples using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods and Cobas 4800 mutation test
Overall Study STARTED	420
Overall Study COMPLETED	420
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Comparison of In-House Methods and Cobas BRAF V600 Mutation Assay in Melanoma Tumor Samples

Baseline characteristics by cohort

Measure	Melanoma Tumor Sample With BRAF V600 Mutation n=420 Participants BRAF V600 mutations were analysed in melanoma tumor samples using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods and Cobas 4800 mutation test
Age, Categorical <=18 years	NA Participants n=5 Participants
Age, Categorical Between 18 and 65 years	NA Participants n=5 Participants
Age, Categorical >=65 years	NA Participants n=5 Participants
Sex: Female, Male Female	NA Participants n=5 Participants
Sex: Female, Male Male	NA Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis. n = number of samples with BRAF V600 mutation by "in-house method".

BRAF V600 mutation status was determined by INCa molecular laboratories "in-house" methods and Cobas 4800 BRAF V600 mutation test. Samples were analysed as V600 mutation, No V600 mutation and Non evaluable. Additionally, the type of V600 mutation (E, K, R, D, E2, other V600 mutation, not specified) was also evaluated only by INCa molecular laboratory "in-house" method.

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=420 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test n=420 Tumor Samples BRAF V600 mutations were analysed using Cobas 4800 mutation test
BRAF Mutation Status According to Cobas 4800 BRAF V600 Mutation Test vs. INCa Laboratories Molecular Genetics Laboratories BRAF V600 mutation - No	264 number of samples	266 number of samples
BRAF Mutation Status According to Cobas 4800 BRAF V600 Mutation Test vs. INCa Laboratories Molecular Genetics Laboratories Non evaluable	6 number of samples	11 number of samples
BRAF Mutation Status According to Cobas 4800 BRAF V600 Mutation Test vs. INCa Laboratories Molecular Genetics Laboratories Type of mutation, V600D, n = 150	1 number of samples	NA number of samples Type of BRAF V600 mutation could not be detected by this method
BRAF Mutation Status According to Cobas 4800 BRAF V600 Mutation Test vs. INCa Laboratories Molecular Genetics Laboratories Type of mutation, V600E, n = 150	133 number of samples	NA number of samples Type of BRAF V600 mutation could not be detected by this method
BRAF Mutation Status According to Cobas 4800 BRAF V600 Mutation Test vs. INCa Laboratories Molecular Genetics Laboratories Type of mutation, V600R, n = 150	2 number of samples	NA number of samples Type of BRAF V600 mutation could not be detected by this method
BRAF Mutation Status According to Cobas 4800 BRAF V600 Mutation Test vs. INCa Laboratories Molecular Genetics Laboratories BRAF V600 mutation- Yes	150 number of samples	143 number of samples
BRAF Mutation Status According to Cobas 4800 BRAF V600 Mutation Test vs. INCa Laboratories Molecular Genetics Laboratories Type of mutation, V600K, n = 150	14 number of samples	NA number of samples Type of BRAF V600 mutation could not be detected by this method

SECONDARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis

The type of tumor sample used for evaluation of BRAF V600 mutation whether it was a biopsy or surgical specimen were reported

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=420 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Tumor Sample Characteristics-Type of Tumor Sample Biopsy	87 number of samples	—
Tumor Sample Characteristics-Type of Tumor Sample Surgical specimen	333 number of samples	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis.

The source of tumor sample for BRAF V600 mutation detection whether taken from internal or external pathology laboratory were reported

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=420 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Tumor Sample Characteristics - Source of Tumor Sample External pathology laboratory	182 number of samples	—
Tumor Sample Characteristics - Source of Tumor Sample Internal pathology laboratory	238 number of samples	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis.

The external or internal pathology laboratories involved in the process of fixation or embedding of the tumor sample was evaluated.

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=420 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Type of Pathology Laboratory Performing the Fixation or Embedding-Pre-analytical Method External pathology laboratory	183 number of samples	—
Type of Pathology Laboratory Performing the Fixation or Embedding-Pre-analytical Method Internal pathology laboratory	237 number of samples	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis.

Time taken from the sampling to the fixation of the tumor sample was reported in range of 0-2 hours, 2-6 hours, >6 hours and unknown. Number of samples falling in each of the class were reported.

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=420 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Time From Sampling to Fixation- Pre-analytical Method 0-2 hours	140 number of samples	—
Time From Sampling to Fixation- Pre-analytical Method 2-6 hours	72 number of samples	—
Time From Sampling to Fixation- Pre-analytical Method >6 hours	3 number of samples	—
Time From Sampling to Fixation- Pre-analytical Method Unknown	205 number of samples	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis.

The different types of fixative Excell, formol, alcohol formol acetic acid and other, used to fix the tumor samples were reported.

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=420 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Type of Fixative Used- Pre-analytical Method Alcohol Formol Acetic acid (AFA)	19 number of samples	—
Type of Fixative Used- Pre-analytical Method Excell	10 number of samples	—
Type of Fixative Used- Pre-analytical Method Formol	389 number of samples	—
Type of Fixative Used- Pre-analytical Method Other	2 number of samples	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis.

Fixation duration is defined as the amount of time required in hours for the fixation of a samples. The fixation duration was categorized as <6 hours, 6-24 hours and >24 hours and unknown. Number of samples falling in each category were reported

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=420 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Fixation Duration by Pre-analytical Method <6 hours	25 number of samples	—
Fixation Duration by Pre-analytical Method 6-24 hours	107 number of samples	—
Fixation Duration by Pre-analytical Method >24 hours	82 number of samples	—
Fixation Duration by Pre-analytical Method Unknown	206 number of samples	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis.

Slice thickness of all the tumour samples was measured. The slice thickness was measured in micrometer.

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=420 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Slice Thickness by Pre-analytical Method	7.1 micrometer (µm) Standard Deviation 4.2	—

SECONDARY outcome

Timeframe: Up to 6 Months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis.

Dewaxing is a method to recover the DNA from samples. Dewaxing information was collected as "Yes, No or Missing"

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=420 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Dewaxing by Pre-analytical Method Missing	0 number of samples	—
Dewaxing by Pre-analytical Method No	39 number of samples	—
Dewaxing by Pre-analytical Method Yes	381 number of samples	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis. Only 341 samples out of 420 were analysed as the information on presence of necrosis was missing for 79 samples in the assessed zones.

The percentage of necrosis defined as the death of one or more cells in the analysed zone was reported.

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=341 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Necrosis Percentage Determination by Pre-analytical Method	3.6 percentage Standard Deviation 8.8	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis.

The percentage of tumor cells in the given tumor sample were reported.

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=420 Participants BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Percentage of Tumor Cells by Pre-analytical Method	70.8 percentage Standard Deviation 20.0	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis. Only available samples were included for analysis.

The tumor samples with presence of melanin were categorized as Important, Few, Medium and Absent.

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=391 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Tumor Samples With Presence of Melanin by Pre-analytical Method Medium	43 number of samples	—
Tumor Samples With Presence of Melanin by Pre-analytical Method Important	19 number of samples	—
Tumor Samples With Presence of Melanin by Pre-analytical Method Absent	202 number of samples	—
Tumor Samples With Presence of Melanin by Pre-analytical Method Few	127 number of samples	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis.

This method assessed DNA from the tumor samples was extracted by Automated method or Manual method.

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=420 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
DNA Extraction - Extraction Method by Pre-analytical Method Automated extraction method	188 number of samples	—
DNA Extraction - Extraction Method by Pre-analytical Method Manual extraction method	232 number of samples	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis.

Median DNA elution volume microliters [mcl] was reported.

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=420 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Median DNA Elution Volume by Pre-analytical Method	100 mcl Interval 25.0 to 185.0	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis.

The DNA concentration in the tissue elute was measured in nanogram per microliter (ng/mcL).

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=420 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Mean DNA Concentration by Pre-analytical Method	155.25 ng/mcl Standard Deviation 206.85	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis.

The total DNA concentration extracted from the tissue was measured in nanogram (ng).

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=420 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Amount of DNA by Pre-analytical Method	11816 ng Standard Deviation 14407	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis.

The method described the size of amplicon used. It was measured in base pairs (bp).

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=420 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Size of Amplicons Used by "In-house" Analytical Method	120 bp Interval 70.0 to 232.0	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis.

Allele-specific PCR, High Resolution Melting (HRM) + Sanger sequencing, Pyrosequencing, Sanger sequencing, Real time PCR, SNaPshot were used for BRAF V600 mutation detection.

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=420 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Method of Mutation Detection by "In-house" Analytical Method Allele-specific PCR	128 number of samples	—
Method of Mutation Detection by "In-house" Analytical Method HRM + Sanger sequencing	118 number of samples	—
Method of Mutation Detection by "In-house" Analytical Method Pyrosequencing	67 number of samples	—
Method of Mutation Detection by "In-house" Analytical Method Real time PCR	26 number of samples	—
Method of Mutation Detection by "In-house" Analytical Method SNaPshot	30 number of samples	—
Method of Mutation Detection by "In-house" Analytical Method Sanger sequencing	51 number of samples	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis.

Total number of samples for whom punch was used in 'in-house analytical' method are reported.

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=420 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Number of Samples Punched in In-house Analytical Method Yes	117 number of samples	—
Number of Samples Punched in In-house Analytical Method No	303 number of samples	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis. Data for the samples where the punch was not used were considered for analysis.

The mean of number of slices per sample when no punch was used are reported.

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=303 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Mean Number of Slices Per Sample Used for "In-house"- Analytical Method	2.6 number of samples Standard Deviation 1.6	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis.

This In-house analytical method measured the time between receipt of samples to the result determination. It measured the time in days.

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=420 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Median Time Between Receipt of Samples and Determination of Result by "In-house" Analytical Method	7 days Interval 1.0 to 30.0	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis.

The working time required by the technician from the time of DNA extraction to the time to obtain the results was measured in hours.

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=420 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Technician Work Time Between DNA Extraction and Result by "In-house" Analytical Method	7 hours Interval 2.0 to 28.0	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis.

The DNA concentration as assessed by COBAS 4800 BRAF V600 Mutation assay was reported. The unit used to measure the DNA concentration was nanogram/microlitre (ng/mcl)

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=420 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Mean DNA Concentration as Measured by COBAS 4800 BRAF V600 Mutation Test-Analytical Method	64.62 ng/mcl Standard Deviation 78.01	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis.

The punch done during Cobas 4800 BRAF V600 Mutation Test on the sample was described as Yes or No.

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=420 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Punch Used for Cobas 4800 BRAF V600 Mutation Test- Analytical Method Yes	45 number of samples	—
Punch Used for Cobas 4800 BRAF V600 Mutation Test- Analytical Method No	375 number of samples	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis. Data for the samples where the punch was No=375, was used for analysis.

This describes the Cobas 4800 BRAF V600 Mutation Test, for the mean of number of slices when No punch method, was used. Of the 420 samples, punch was Yes, for 45 samples and punch was No, for 375 samples.

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=375 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Number of Slices Used When No Punch Was Used for Cobas 4800 BRAF V600 Mutation Test- Analytical Method	2.3 number of samples Standard Deviation 1.6	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis.

This analytical method for cobas 4800 BRAF V600 Mutation Test measured the time between receipt of samples to the result determination. It measured the time in days.

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=420 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Median Time Between Receipt of Sample and Determination of Result by Cobas 4800 BRAF V600 Mutation Test -Analytical Method	6 days Interval 1.0 to 98.0	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All samples meeting the inclusion criteria and not meeting the exclusion criteria were considered for analysis.

This cobas 4800 BRAF V600 Mutation Test analytical method measures the working time required by the technician from the time of DNA extraction to the time to obtain the results. The time duration was measured in hours.

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=420 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Technician Work Time Between DNA Extraction and Result by Cobas 4800 BRAF V600 Mutation Test - Analytical Method	5 hours Interval 1.0 to 15.0	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: The discordant sample population is defined as the samples whose result for BRAF V600 mutation by the "in-house" method did not show similar outcome with the cobas 4800 mutation test.

Crossing DNA, DNA from In-House method analysed with cobas, SNaPshot, DNA from cobas analysed with In-House method, external site control test, Sanger sequencing, Kit CE-IVD Therascreen RGQ Qiagen, Kit Therascreen RGQ BRAF + Pyrosequencing by another platform (PF), Pyrosequencing, Mutation detection On Another Block, (primitive tumor [prm. tmr]), Sequencing And Therascreen kit (Qiagen) were used for management of discordance between "in-house" method and Cobas 4800 mutation test.

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=28 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Management of Discordance- Method Used to Manage Discordance SNaPshot	4 number of samples	—
Management of Discordance- Method Used to Manage Discordance DNA from cobas analysed with In-House method	2 number of samples	—
Management of Discordance- Method Used to Manage Discordance Mutation detection on other Block, (prm. tmr)	1 number of samples	—
Management of Discordance- Method Used to Manage Discordance Crossing DNA	7 number of samples	—
Management of Discordance- Method Used to Manage Discordance DNA from In-House method analysed with cobas	6 number of samples	—
Management of Discordance- Method Used to Manage Discordance External site control test	2 number of samples	—
Management of Discordance- Method Used to Manage Discordance Sanger sequencing	2 number of samples	—
Management of Discordance- Method Used to Manage Discordance Kit CE-IVD Therascreen RGQ Qiagen	1 number of samples	—
Management of Discordance- Method Used to Manage Discordance KIT THERASCREEN RGQ BRAF+PYROSEQ. by other PF	1 number of samples	—
Management of Discordance- Method Used to Manage Discordance Pyrosequencing	1 number of samples	—
Management of Discordance- Method Used to Manage Discordance Sequencing and Therascreen kit (Qiagen)	1 number of samples	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: The discordant sample population is defined as the samples whose result for BRAF V600 mutation by the "in-house" method did not show similar outcome with the cobas 4800 mutation test.

The final results obtained by discordance management of the 28 discordant samples were BRAF V600 mutation, No BRAF V600 mutation and Non-evaluable. These results were further assessed by the Investigator and interpreted as final result.

Outcome measures

Measure	INCa Molecular Genetics Laboratory "in House" Methods n=28 Tumor Samples BRAF V600 mutations were analysed using INCa (Institut National du Cancer \[French National Cancer Institute\]) molecular genetics laboratories using "in-house" methods	Cobas 4800 Mutation Test BRAF V600 mutations were analysed using Cobas 4800 mutation test
Management of Discordance-Final Result for BRAF V600 Mutation Detection BRAF V600 mutation	19 number of samples	—
Management of Discordance-Final Result for BRAF V600 Mutation Detection No BRAF V600 mutation	7 number of samples	—
Management of Discordance-Final Result for BRAF V600 Mutation Detection Non evaluable	2 number of samples	—

Adverse Events

INCa Molecular Genetics Laboratory "in House" Methods

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Cobas 4800 Mutation Test

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Roche Trial Information Hotline

F. Hoffmann-La Roche AG

Phone: +41 61 6878333

Email: global.trial_information@roche.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER