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The study will evaluate the efficacy of targeted therapy based on tumor molecular profiling versus conventional chemotherapy in patients with advanced cancer using each patient as its own control. This study is a study involving patients with advanced cancer. All types of solid tumors will be allowed in the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| research of druggable molecular alterations on tumor biopsy | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| research of druggable molecular alterations on tumor biopsy | Diagnostic Test | The study will run in 2 steps. Before starting a new treatment, patients with advanced cancer will undergo a tumor biopsy of a metastatic site in order to perform molecular analyses seeking for druggable molecular alterations |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of patients with a PFS2 to PFS1 ratio superior to 1.5. | PFS1 is defined as the time to a documented progression under conventional therapy according to RECIST 1.1. PFS2 is defined as the time to a documented progression or death when patients are treated by targeted therapy according to RECIST 1.1 | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Overall response rate (ORR) on both treatments | Evaluation of the best objective response rate (ORR) for each treatment according to RECIST 1.1 The best ORR is the best response reached during treatment according to RECIST 1.1 criteria. | 3 years |
| Overall survival (OS) |
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Inclusion criteria:
Inclusion will proceed in 2 steps. First step for molecular analyses and second step in order to be included in the efficacy analysis.
Inclusion criteria for Step 1:
3) Disease amenable to biopsy 5) ECOG performance status of 0 or 1 6) Measurable disease 7) Adequate renal function defined by a serum creatinine <1.5xUNL (upper normal limit) 8) Adequate liver function test defined by SGOT & SGPT <3xUNL (5xUNL in case of liver metastases), and bilirubin level <1.5xUNL 9) Adequate bone marrow function defined by platelets >100,000/mm3, hemoglobin >9 g/dL, and neutrophils >1,000/mm3 10) Patient must be affiliated to the French Social Security System 11) Signed informed consent 12 For female of child-bearing potential: a negative pregnancy test <72 hours before starting study treatment is required. If sexually active, female of childbearing potential must use "highly effective" methods of contraception for the study duration and for 3 months following the last treatment 13) For male of reproductive potential: any sexually active male patient must use a condom while on study treatment and for 3 months following the last treatment
Inclusion criteria for Step 2:
Exclusion criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institut Bergonié | Bordeaux | 33076 | France | |||
| Centre LEON BERARD |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32750212 | Derived | Dupain C, Masliah-Planchon J, Gu C, Girard E, Gestraud P, Du Rusquec P, Borcoman E, Bello D, Ricci F, Hescot S, Sablin MP, Tresca P, de Moura A, Loirat D, Frelaut M, Vincent-Salomon A, Lecerf C, Callens C, Antonio S, Franck C, Mariani O, Bieche I, Kamal M, Le Tourneau C, Servois V. Fine-needle aspiration as an alternative to core needle biopsy for tumour molecular profiling in precision oncology: prospective comparative study of next-generation sequencing in cancer patients included in the SHIVA02 trial. Mol Oncol. 2021 Jan;15(1):104-115. doi: 10.1002/1878-0261.12776. Epub 2020 Sep 15. |
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Investigators will share de-identified data sets with interested researchers, educators or clinicians. Materials generated under the project will be disseminated in accordance with Institut Curie policies.
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Data requests can be submitted starting 9 months after article publication and will be made accessible for up to 12 months.
Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific reserach, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).
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|
Evaluation of overall survival (OS) defined as the time between inclusion and death, whatever the cause is. Alive patients will be censored at their last known contact date. |
| 3 years |
| number of grade 3 or 4 adverse events and grade 1 or 2 adverse events that lead to dose modification or interruption | Evaluation of toxicities related to treatments according to CTCAE v4.03. Only grade 3 or 4 adverse events and grade 1 or 2 adverse events that lead to dose modification or interruption | 3 years |
| Ability of ctDNA to detect molecular alterations identified on tumor biopsies | Percentage of patients for whom all druggable molecular alterations detected on the tumor biopsy are also detected on ctDNA. | at baseline |
| Ability of fine-needle aspiration cytology to detect molecular alterations identified on tumor biopsies | Percentage of patients for whom all druggable molecular alterations detected on the tumor biopsy are also detected on fine-needle aspiration cytology | at baseline |
| Ability of sequential ctDNA sampling to predict response/resistance to treatment | Changes in ctDNA levels and molecular alterations observed at different time points. | through study completion, every 2 months |
| Proportion of patients with a PFS2 to PFS1 ratio superior to 1.5, including patients who were treated with matched therapy based on a molecular alteration outside of RAF/MEK pathway | PFS1 is defined as the time to a documented progression under conventional therapy according to RECIST 1.1. PFS2 is defined as the time to a documented progression or death when patients are treated by targeted therapy according to RECIST 1.1 | 3 years |
| Lyon |
| 69373 |
| France |
| Institut Curie | Paris | 75005 | France |
| Institut Curie Hôpital René Huguenin | Saint-Cloud | 92210 | France |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
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