Proof -of -Concept Study To Stratify Targeted Therapies Adapted To Molecular Profiling

  • STATUS
    Recruiting
  • End date
    Jan 23, 2022
  • participants needed
    700
  • sponsor
    Gustave Roussy, Cancer Campus, Grand Paris
Updated on 23 January 2021

Summary

In the light of the development of high-throughput technologies enabling a biology-based reclassification of tumors and the increasing number of available specifically targeting anticancer agents the era of "precision medicine" has begun. Several clinical precision medicine trials with the aim of stratifying treatment according to molecular profiles (for example in France: 'MOlecular Screening for CAncer Treatment Optimization' MOSCATO-01, SHIVA, PROFILER, Safir01, Safir02) are ongoing in adults and have shown the feasibility of this approach. MOSCATO-01 is the first trial worldwide including pediatric patients, performing an on-purpose intervention and molecular profiling in recurrent tumors. Together with more than 500 adult patients, between December 2012 to August 2014, the tumors of 35 children and adolescents have been profiled, confirming that this approach is feasible in pediatric patients albeit with accelerated time stringencies. Importantly, the results of the first children and adolescents profiled showed that 2/3 of patients had 'actionable' alterations using hot spot mutations sequencing and CGH array (Geoerger B et al, ASCO 2014).

The project 'MAPPYACTS' will use both Whole Exome Sequencing (WES) and RNA Sequencing of tumor tissue to increase the number of targetable genomic alterations. Furthermore to improve understanding of the overall molecular profile and possible response to treatment, methylation array, miRNA expression profiles, and study of immunomodulators will be performed on tumor samples subsequently. CLIP2 (INCa-labeled early phase clinical trials centers) - SiRIC (INCa- labeled comprehensive cancer centers) molecular profiling and bioinformatics platforms will contribute with their expertise in molecular profiling projects and characterization of pediatric cancers. Data interpretation of molecular genetic alterations detected by WES and RNA Seq and treatment recommendation will be done within a multidisciplinary therapeutic molecular biology tumor board.

'MAPPYACTS' will produce one of the largest cohorts of molecularly characterized relapsed tumors reported to date, and thanks to increased access to clinical trials since the European pediatric legislation, the investigators expect that 20-30% of patients can be stratified into a targeted trial based on the detected profile.

It is the investigators' intention that this initiative paves the way to enrich ongoing clinical targeted agent trials, to increase the numbers of stratified clinical trials, to an earlier access to targeted agents, and will play a crucial role in the relevant development of these new agents in pediatric malignancies.

Details
Condition Relapsed or Refractory Pediatric Tumor
Treatment biopsy or surgical resection of tumor and blood sampling
Clinical Study IdentifierNCT02613962
SponsorGustave Roussy, Cancer Campus, Grand Paris
Last Modified on23 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Written informed consent signed by the patient, or parents or legal representative and assent of the minor child to perform biopsy/surgical resection/aspiral/sample and molecular analysis of the tumor and blood sample
Patient with confirmed solid tumor or leukemia which is recurrent or refractory to standard treatment and who is eligible for an early phase clinical trial
In case of solid tumor, lesion must be accessible for biopsy or surgical resection or cytological puncture
Age: Patients aged 6 months at time of inclusion and aged 18 years at the time of initial diagnosis
Performance status and life expectancy that allows treatment in an experimental trial: Karnofsky performance status 70% for patients > 12 years of age, Lansky play scale 70% for patients 12 years of age
Adequate organ function
Adequate hematopoietic function for patients with solid tumor (Leukemia
patients are excluded from hematological criteria) : Neutrophils >1.0 x 109/l
Platelets >100 x 109/l, Heamoglobin >80 g/l (transfusion allowed) In case of
bone marrow involvment: Neutrophils >/= 0.75 x 109/l (unsupported) , Platelet
count >/= 0.75 x 109/l (unsupported) Adequate hepatic function: ALAT/ASAT <2.5
x ULN, Bilirubin 1.5 x ULN (in case of tumor involvement of the liver
ALAT/ASAT <5 x ULN) Adequate renal function: Serum creatinemia <1.5 x ULN for
age. In case serum creatinine >1.5 ULN according to age, creatinine clearance
has to be >70mL/mL/1.73 m2 or glomerular filtration rate measurement >70% of
the expected value
Patients affiliated to a Social Security Regimen or beneficiary of the same as per local regulatory requirements

Exclusion Criteria

Life expectancy 3 months
Symptomatic CNS metastases
In case of leukemia, are excluded patients with isolated meningitis relapses
Coagulation disorder that prevents the accomplishment of a biopsy or surgery
Uncontrolled infections not responsive to antibiotics, antiviral medicines, or antifungal medicines
Presence of CTCAE grade 2 toxicity (except alopecia, ototoxicity, lymphopenia which are not excluded if grade 3 or less) due to prior cancer therapy
Malignant disease other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 3 years prior to study entry
Any concurrent illness or laboratory abnormality that in opinion of investigator may interfere with the interpretation of study results, may suppose a risk for the realization of biopsy/surgery, and in the judgment of the investigator would make the patient inappropriate for the study
Evidence of active viral Hepatitis B or C or known diagnosis of human immunodeficiency virus infection
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