SHIVA02 - Evaluation of the Efficacy of Targeted Therapy Based on Tumor Molecular Profiling in Patients With Advanced Cancer Using Each Patient as Its Own Control (SHIVA02) (SHIVA02)

• ClinicalTrials.gov Identifier: NCT03084757
• Recruitment Status: Active, not recruiting
• First Posted: March 21, 2017
• Last Update Posted: May 20, 2022
• Sponsor: Institut Curie
• Information provided by (Responsible Party): Institut Curie

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cancer; Solid Tumor, Adult	Diagnostic Test: research of druggable molecular alterations on tumor biopsy	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 170 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Screening
• Official Title: SHIVA02 - Evaluation of the Efficacy of Targeted Therapy Based on Tumor Molecular Profiling in Patients With Advanced Cancer Using Each Patient as Its Own Control
• Actual Study Start Date: May 26, 2017
• Estimated Primary Completion Date: September 26, 2022
• Estimated Study Completion Date: November 26, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: research of druggable molecular alterations on tumor biopsy	Diagnostic Test: research of druggable molecular alterations on tumor biopsy; 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

Outcome Measures

Primary Outcome Measures :

1. Proportion of patients with a PFS2 to PFS1 ratio superior to 1.5. [ Time Frame: 3 years ]
   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

Secondary Outcome Measures :

1. Overall response rate (ORR) on both treatments [ Time Frame: 3 years ]
   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.
2. Overall survival (OS) [ Time Frame: 3 years ]
   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. number of grade 3 or 4 adverse events and grade 1 or 2 adverse events that lead to dose modification or interruption [ Time Frame: 3 years ]
   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
4. Ability of ctDNA to detect molecular alterations identified on tumor biopsies [ Time Frame: at baseline ]
   Percentage of patients for whom all druggable molecular alterations detected on the tumor biopsy are also detected on ctDNA.
5. Ability of fine-needle aspiration cytology to detect molecular alterations identified on tumor biopsies [ Time Frame: at baseline ]
   Percentage of patients for whom all druggable molecular alterations detected on the tumor biopsy are also detected on fine-needle aspiration cytology
6. Ability of sequential ctDNA sampling to predict response/resistance to treatment [ Time Frame: through study completion, every 2 months ]
   Changes in ctDNA levels and molecular alterations observed at different time points.
7. 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 [ Time Frame: 3 years ]
   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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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:

1. Patient with recurrent/metastatic solid tumor who failed or are not candidate for treatments usually proposed in first intention and for whom a prospective clinical trial has been indicated in a tumor board
2. Patient with a documented progression before the start of conventional therapy according to RECIST 1.1.
3. Patient ≥18 years old

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:

1. Patient for whom the Molecular Biology Board (MBB) has identified a druggable molecular alteration of the RAF/MEK signaling pathway and a treatment recommendation has been established by the MBB.
2. Patient with a documented progression during the conventional therapy according to RECIST 1.1.
3. Patient with imaging performed within 28 days prior to the planned start date of treatment

Exclusion criteria:

1. Patients below 18 years old
2. Patients with CNS involvement that has not been controlled for >3 months
3. Patients planned to receive a molecularly targeted agent
4. Patients who are candidate to receive a molecularly targeted agent that is approved for their disease
5. Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, including uncontrolled diabetes, cardiac disease, uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infection within one year, chronic liver or renal disease, active gastrointestinal tract ulceration, severely impaired lung function
6. Pregnant and/or breastfeeding women
7. Patients individually deprived of liberty or placed under the authority of a tutor
8. Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
9. Known HIV, HBV, or HCV infection

Contacts and Locations

Locations

France

Institut Bergonié

Bordeaux, France, 33076

Centre LEON BERARD

Lyon, France, 69373

Institut Curie

Paris, France, 75005

Institut Curie Hôpital René Huguenin

Saint-Cloud, France, 92210

Sponsors and Collaborators

Institut Curie

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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, Bièche 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.

• Responsible Party: Institut Curie
• ClinicalTrials.gov Identifier: NCT03084757
• Other Study ID Numbers: IC 2016-06
• First Posted: March 21, 2017
• Last Update Posted: May 20, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No