Metastatic Solid Tumors
Conditions
Keywords
Solid tumor, Metastatic, NTRK
Brief summary
This retrospective study has a primary objective to estimate the incidence of NTRK gene fusion depending on the histological diagnosis.
Detailed description
This retrospective study has a primary objective to estimate the incidence of NTRK gene fusion depending on the histological diagnosis. The tropomyosin receptor kinase (Trk) receptor family comprises 3 transmembrane proteins referred to as Trk A, B and C (TrkA, TrkB and TrkC) receptors that are encoded by the NTRK1, NTRK2 and NTRK3 genes, respectively. These receptor tyrosine kinases are expressed in human neuronal tissue and play an essential role in the physiology of development and function of the nervous system through activation by neurotrophins. Gene fusions involving NTRK genes lead to transcription of chimeric Trk proteins with constitutively activated or overexpressed kinase function conferring oncogenic potential. These genetic abnormalities have recently emerged as targets for cancer therapy, because novel compounds have been developed that are selective inhibitors of the constitutively active rearranged proteins. Developments in this field are being aided by next generation sequencing methods as tools for unbiased gene fusions discovery. However, the incidence of NTRK aberrations in solid tumors is unknown as well as the natural history of NTRK-rearranged tumors This study will provide better knowledge of NTRK gene fusion incidence to allow recommendations for pathological diagnosis. Subjects who are tested positive by Immunohistochemistry (IHC : Pan-Trk IHC testing with mAb EPR17341) will be the subject of molecular assays such as next-generation sequencing (Archer Dx fusion assay) of tumor material \[parrafin embedded material\]), so that tumor harboring NTRK1, NTRK2 or NTRK3 gene fusions, is identified properly.
Interventions
OTHERNo intervention (this is a retrospective cohort study)
No intervention (this is a retrospective cohort study) aimed at describing tumour samples. No treatment/intervention is being tested.
Sponsors
Bayer
Institut Bergonié
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
1 Months to 100 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥ 1 month. * Subject has/had a histologically or cytologically confirmed diagnosis of solid tumor including but not exclusively: soft tissue sarcoma, BRAF wild type melanoma, KRAS wild-type colorectal cancer, central nervous system, EGFR-wild type non-small cell lung cancer. * Subject has locally advanced/unresectable or metastatic disease. * Subject has received at least one systemic anti-cancer therapy for locally advanced/unresectable or metastatic disease for which there is available outcome information in terms of PFS, or the latter can be estimated based on the subject's records. * Subject has tumor material available for immunoscreening (IHC for NTRK gene fusions). * Written and voluntary informed consent understood, signed and dated, or a waiver of consent is granted according to French régulations.
Exclusion criteria
• Subjects who have not yet received or completed at least one systemic anti-cancer therapy for locally advanced/unresectable or metastatic cancer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Count of Participants With NRTK Fusions Among Participants Analyzed by NGS (Next-generation Sequencing). | at baseline (i.e. at the time of tumor removal) | A participant with NRTK fusion is defined as a participant with a tumor harboring NTRK1, NTRK2 or NTRK3 gene fusions, based on NGS (Next-generation sequencing methods). NGS (Next-generation sequencing methods) method: DNA and RNA were extracted from tumor tissue according to standard procedures. All samples had their RNA analyzed with Archer or full RNA sequencing to assess specific novel NTRK1, 2, and 3 rearrangements for the production of NTRK fusion transcripts. Alternatively, DNA was analyzed by using an hybrid-capture based NGS assay as previously described. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Count of Participants With NRTK Fusions Among Participants With With Positive Immunohistochemistry (IHC) | at baseline (i.e. at the time of tumor removal) | A participant with NRTK fusion is defined as a participant with a tumor harboring NTRK1, NTRK2 or NTRK3 gene fusions, based on Immunohistochemistry (IHC). Immunohistochemistry (IHC) mehtod : Pan-TRK: rabbit monoclonal antibody, clone C17F1, Cell signaling dilution 1/50°. Automate Benchmark: ULTRA Ventana, CC1 64', incubation 52', revelation kit Optiview |
Other
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) in Patients With NRTK Gene Fusion. | Two years after tumor removal | PFS is calculated using Kaplan-Meier method, in the population of patients with positive IHC results. |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Subjects With Locally Advanced/Unresectable or Metastatic Solid Tumors Tumor material was tested by immunohistochemistry (Pan-Trk ICH testing with mAb EPR17341). Tumor material tested positive were analyzed by next-generation sequencing to identify NTRK1, NTRK2 or NTRK3 gene fusions. | 3,820 |
| Total | 3,820 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | IHC not performed | 2,299 |
Baseline characteristics
| Characteristic | Subjects With Locally Advanced/Unresectable or Metastatic Solid Tumors | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 0 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment France | 3820 participants | — |
| Sex: Female, Male Female | 0 Participants | — |
| Sex: Female, Male Male | 0 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 0 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Count of Participants With NRTK Fusions Among Participants Analyzed by NGS (Next-generation Sequencing).
A participant with NRTK fusion is defined as a participant with a tumor harboring NTRK1, NTRK2 or NTRK3 gene fusions, based on NGS (Next-generation sequencing methods). NGS (Next-generation sequencing methods) method: DNA and RNA were extracted from tumor tissue according to standard procedures. All samples had their RNA analyzed with Archer or full RNA sequencing to assess specific novel NTRK1, 2, and 3 rearrangements for the production of NTRK fusion transcripts. Alternatively, DNA was analyzed by using an hybrid-capture based NGS assay as previously described.
Time frame: at baseline (i.e. at the time of tumor removal)
Population: Subjects with locally advanced/unresectable or metastatic solid tumors and for whom NGS (new generation sequencing) was performed
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Subjects With Locally Advanced/Unresectable or Metastatic Solid Tumors and NGS Performed. | Count of Participants With NRTK Fusions Among Participants Analyzed by NGS (Next-generation Sequencing). | 11 Participants |
Secondary
Count of Participants With NRTK Fusions Among Participants With With Positive Immunohistochemistry (IHC)
A participant with NRTK fusion is defined as a participant with a tumor harboring NTRK1, NTRK2 or NTRK3 gene fusions, based on Immunohistochemistry (IHC). Immunohistochemistry (IHC) mehtod : Pan-TRK: rabbit monoclonal antibody, clone C17F1, Cell signaling dilution 1/50°. Automate Benchmark: ULTRA Ventana, CC1 64', incubation 52', revelation kit Optiview
Time frame: at baseline (i.e. at the time of tumor removal)
Population: Participants with positive IHC results
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Subjects With Locally Advanced/Unresectable or Metastatic Solid Tumors and NGS Performed. | Count of Participants With NRTK Fusions Among Participants With With Positive Immunohistochemistry (IHC) | 1 Participants |
Other Pre-specified
Progression-free Survival (PFS) in Patients With NRTK Gene Fusion.
PFS is calculated using Kaplan-Meier method, in the population of patients with positive IHC results.
Time frame: Two years after tumor removal
Population: Only one patient had positive IHC results and had a gene NRTK fusion.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Subjects With Locally Advanced/Unresectable or Metastatic Solid Tumors and NGS Performed. | Progression-free Survival (PFS) in Patients With NRTK Gene Fusion. | NA years |