Clinical trial NCT03084757: 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)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Cancer
Solid Tumor, Adult
Lead sponsor: Institut Curie
Sponsor class: OTHER
First posted: 2017-03-21
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

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.


Eligibility 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

Primary outcomes:
measure: Proportion of patients with a PFS2 to PFS1 ratio superior to 1.5.
timeFrame: 3 years
Secondary outcomes:
measure: Overall response rate (ORR) on both treatments
timeFrame: 3 years
measure: Overall survival (OS)
timeFrame: 3 years
measure: number of grade 3 or 4 adverse events and grade 1 or 2 adverse events that lead to dose modification or interruption
timeFrame: 3 years
measure: Ability of ctDNA to detect molecular alterations identified on tumor biopsies
timeFrame: at baseline
measure: Ability of fine-needle aspiration cytology to detect molecular alterations identified on tumor biopsies
timeFrame: at baseline
measure: Ability of sequential ctDNA sampling to predict response/resistance to treatment
timeFrame: through study completion, every 2 months
measure: 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
timeFrame: 3 years
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Institut Bergonié
city: Lyon
country: France
facility: Centre LEON BERARD
city: Paris
country: France
facility: Institut Curie
city: Saint-Cloud
country: France
facility: Institut Curie Hôpital René Huguenin
Study officials:
References:
citation: 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.