A Study Evaluating the Activity of Anti-cancer Treatments Targeting Tumor Molecular Alterations/Characteristics in Advanced / Metastatic Tumors.

Sponsor
Centre Leon Berard
Study ID
NCT04116541
Phase
PHASE2
Status
Recruiting
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Conditions

  • Malignant Solid Tumor

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • HDM201 — DRUG
    HDM201 120mg, Every 3 weeks, Per os
  • Ribociclib — DRUG
    Ribociclib 200mg/day, once daily 2 weeks on/1 week off, Per os
  • Cabozantinib — DRUG
    Cabozantinib, 60 mg /day, continuous, Per os
  • Alectinib — DRUG
    Alectinib, 600mg twice daily, Per os
  • Regorafenib — DRUG
    Regorafenib 160mg, once daily, 3 weeks on/1 week off, Per os
  • Trametinib — DRUG
    Trametinib 2 mg/day, continuous, Per os
  • Dabrafenib — DRUG
    Dabrafenib 150 mg twice daily, Per os
  • Avapritinib — DRUG
    300 mg/day,continuous, Per os

Study Details

This trial is a multicenter, open-label, biology driven, phase II study using a sequential Bayesian design, aiming to assess the efficacy and safety of different Matched Targeted Therapy (MTT) in independent and parallel cohorts of treatment. Patients will be assigned to a treatment cohort based on molecular alterations/characteristics detected on tumor sample from primary tumor or metastatic lesion. In this protocol, several MTTs treatment cohorts are planned. This study is designed with the flexibility to open new MTTs treatment cohorts and to close existing MTTs treatment cohorts that demonstrate no clinical benefit. Each treatment cohort will be driven separately even though procedures, quality control and reporting, will be common. The protocol will be amended in order to include new treatments or combinations that emerge as being of interest for patients with advanced/metastatic cancers. All eligible patients will receive study drugs as long as patient experiences clinical benefit in the opinion of the investigator, or until unacceptable toxicity, or until symptomatic deterioration attributed to disease progression as determined by the investigator after an integrated assessment of radiographic data and clinical status, or withdrawal of consent. Patients will be permitted to continue study treatment after progressive disease according to RECIST v1.1 if they meet all of the following criteria and following validation of the Sponsor: * Evidence of clinical benefit as assessed by the investigators, * Absence of symptoms and signs (including worsening of laboratory values; e.g., new or worsening hypercalcemia) that indicate unequivocal progression of disease, * No decline in ECOG Performance Status (PS) that can be attributed to disease progression.

Key Dates

Start date
Jan 28, 2020
Status verified
Apr 2026
Primary completion
Oct 31, 2026
Completion
Oct 31, 2027

Study Design

Enrollment
455 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: HDM201 + Ribociclib
    Patient with documented amplification of Cyclin-dependent kinase 6 (CDK6) and/or Cyclin-dependent kinase 4 (CDK4), and/or cyclin dependent kinase inhibitor 2A (CDKN2A) homozygous deletion, and/or amplification of Cyclin D1 (CCND1) and/or Cyclin D3 (CCND3) with no deletion/losses more than single copy of retinoblastoma 1 (RB1) by copy number and P53 wild-type detected on tumor sample from primary tumor or metastatic lesion.
  • Experimental: Cabozantinib
    Patient with AXL, MET, vascular endothelial growth factor receptor (VEGFR), vascular endothelial growth factor (VEGF), RET, ROS1, MER, Tropomyosin receptor kinase B (TRKB),TIE-2 and/or Tyro3 activating mutations and/or amplification, and/or NTRK translocation and/or ROS1 translocation, and/or MET translocation detected on tumor sample from primary tumor or metastatic lesion.
  • Experimental: Alectinib
    Activating ALK alterations: translocation, or selected mutations,), or activating rearrangements following validation by central molecular tumor board of Centre Léon Bérard.
  • Experimental: Regorafenib
    Patient with Activating mutation and/or amplification and/or rearrangement of VEGFR1-3, TIE-2, KIT, RET, RAF1, BRAF (other than V600 mutations), CRAF, HRAS , PDGFR, FGFR1-2, FLT3 and/or CSF1R, and/or amplification of the ligands, and/or biallelic inactivation of SMAD4, following validation by central molecular tumor board of Centre Léon Bérard.
  • Experimental: Trametinib
    Patient with activating mutation and/or amplification of KRAS (except all KRAS G12 mutations), NRAS, HRAS and/or Mitogen-Activated Protein Kinase Kinase (MAP2K); and/or biallelic inactivation of Neurofibromin 1 (NF1); and/or activating mutation Protein Tyrosine Phosphatase Non-Receptor Type 11 (PTPN11); and/or amplification or translocation of BRAF ; and/or translocation RAF1
  • Experimental: Trametinib + Dabrafenib
    Patient with BRAF V600 mutation
  • Experimental: Avapritinib
    Activating mutations of KIT exon 17 or PDGFRA exon 18 associated or not to mutation on KIT exon 11 or PDGFRA exon 12/14

Primary Outcome Measure

Progression free rate after 3 months (12 weeks) of treatment [ Time Frame: 3 months (12 weeks) ]

Central Contacts

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