Clinical Trial Results:
A study to select rational therapeutics based on the analysis of matched tumor and normal biopsies in subjects with advanced malignancies
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Summary
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EudraCT number |
2013-000914-38 |
Trial protocol |
ES |
Global end of trial date |
31 Dec 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
13 Nov 2021
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First version publication date |
13 Nov 2021
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
WINTHER
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01856296 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
VHIR
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Sponsor organisation address |
Passeig Vall Hebron 119-129, Barcelona, Spain, 08035
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Public contact |
Joaquin Lopez-Soriano, VHIR, +34 934894779, joaquin.lopez.soriano@vhir.org
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Scientific contact |
Clinical Trials Office, Vall d'Hebron Institute of Oncology (VHIO), +34 9327460004922, gsala@vhio.net
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
31 Dec 2015
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Dec 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess the individual outcome of patients with advanced malignancies, by comparing the progression-free survival (PFS) using a treatment regimen selected by a molecular analysis of a patient?s tumor with the PFS for the most recent regimen on which the patient had experienced progression
- ARM A : PFS2/PFS1 >1.5 in 50% of patients
- ARM B : PFS2/PFS1 >1.5 in 40% of patients
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Protection of trial subjects |
Patients had a fresh biopsy of tumor and corresponding normal tissue after they enrolled in the study, and these biopsies were used for the genomic and transcriptomic assays, which determined the tretament
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 May 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 60
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Country: Number of subjects enrolled |
Canada: 20
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Country: Number of subjects enrolled |
Israel: 7
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Country: Number of subjects enrolled |
France: 20
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Worldwide total number of subjects |
107
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EEA total number of subjects |
80
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
80
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From 65 to 84 years |
27
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85 years and over |
0
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Recruitment
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Recruitment details |
The patients were accrued at four centers located in four countries: Spain, Israel, France and Canada, from April 2013 to December 2015. Patients had advanced cancers that had progressed on standard treatment. | |||||||||
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Pre-assignment
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Screening details |
Consented patients underwent a dual biopsy from the metastasis and from the histologically matched normal tissue | |||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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DNA screening | |||||||||
Arm description |
Tumor specimens collected for tissue NGS analysis were sent directly to Foundation Medicine. The FoundationOne genomic assay (http://www.foundationone.com/) (Clinical Laboratory Improvement Assessment-approved standards) assessed genetic alterations from the entire coding sequence of 236 cancer-related genes, plus rearrangements found in introns of an additional 28 cancer-related genes. Equivocal amplification in this assay refers to copy number 6 or 7, whereas amplification means copy number ≥8 (except for ERBB2, for which equivocal amplification means copy number 5 or 6 and amplification means copy number ≥7). To be reported by the FoundationOne assay, specific alterations must have been identifiable in at least 10% of tumor DNA and a sequencing coverage of 500 × | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Trastuzumab
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Investigational medicinal product code |
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Other name |
ERBB2 antibody
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Depending on patient and center
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Investigational medicinal product name |
Vemurafenib
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Investigational medicinal product code |
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Other name |
BRAF inhibitor
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Depending of patient and center
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Arm title
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RNA screening | |||||||||
Arm description |
All patients included in the study, whatever the status of their DNA analysis, had an analysis of their transcriptome attempted. But, per protocol, the transcriptomic information was only considered for navigation to a therapy in cases that had no match found or therapy available per arm A (DNA). The drug selection in arm B is based on the biological characteristics of the tumor of the individual to be treated in comparison to a normal sample from the same individual. Based on a score calculated (examining deregulated target genes), the match between genes deregulated to a literature-derived knowledge base of gene-drug-directed connections, the relative efficacy of the drugs was predicted for the individual. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Trastuzumab
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Investigational medicinal product code |
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Other name |
ERBB2 antibody
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Depending on patient and center
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Investigational medicinal product name |
Vemurafenib
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Investigational medicinal product code |
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Other name |
BRAF inhibitor
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Depending of patient and center
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End points reporting groups
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Reporting group title |
DNA screening
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Reporting group description |
Tumor specimens collected for tissue NGS analysis were sent directly to Foundation Medicine. The FoundationOne genomic assay (http://www.foundationone.com/) (Clinical Laboratory Improvement Assessment-approved standards) assessed genetic alterations from the entire coding sequence of 236 cancer-related genes, plus rearrangements found in introns of an additional 28 cancer-related genes. Equivocal amplification in this assay refers to copy number 6 or 7, whereas amplification means copy number ≥8 (except for ERBB2, for which equivocal amplification means copy number 5 or 6 and amplification means copy number ≥7). To be reported by the FoundationOne assay, specific alterations must have been identifiable in at least 10% of tumor DNA and a sequencing coverage of 500 × | ||
Reporting group title |
RNA screening
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Reporting group description |
All patients included in the study, whatever the status of their DNA analysis, had an analysis of their transcriptome attempted. But, per protocol, the transcriptomic information was only considered for navigation to a therapy in cases that had no match found or therapy available per arm A (DNA). The drug selection in arm B is based on the biological characteristics of the tumor of the individual to be treated in comparison to a normal sample from the same individual. Based on a score calculated (examining deregulated target genes), the match between genes deregulated to a literature-derived knowledge base of gene-drug-directed connections, the relative efficacy of the drugs was predicted for the individual. | ||
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End point title |
PFS2/PFS1>1.5 | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
End of study
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Statistical analysis title |
PFS2/PFS1 > 1.5 | ||||||||||||
Comparison groups |
DNA screening v RNA screening
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Number of subjects included in analysis |
107
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.48 | ||||||||||||
Method |
Fisher exact | ||||||||||||
Confidence interval |
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End point title |
Median PFS | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
All the study
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Stable Disease | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
All the study
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Statistical analysis title |
Stable Disease | ||||||||||||
Comparison groups |
DNA screening v RNA screening
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Number of subjects included in analysis |
107
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.37 | ||||||||||||
Method |
Fisher exact | ||||||||||||
Confidence interval |
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Adverse events information [1]
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Timeframe for reporting adverse events |
End of study
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
22
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Reporting groups
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Reporting group title |
Spanish patients
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Reporting group description |
Assay was only considered as a Clinical Trial in Spain. So only data are available in this country on adverse events. No non-seriuos events were reported. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Given the status of patients, all the detected adverse events were considered as serious. |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Patients had heavily pretreated disease, which may have limited capacity for response. Number of patients per arm was small. Trial was not designed to compare arms. Participating centers were located over a wide geographical territory. | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/31011205 |
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