European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors

Sponsor
Gustave Roussy, Cancer Campus, Grand Paris
Study ID
NCT02813135
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

  • Pediatric Cancer

Eligibility Criteria

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

Interventions

  • Ribociclib — DRUG
  • Topotecan — DRUG
  • Temozolomide — DRUG
  • Everolimus — DRUG
  • Adavosertib — DRUG
  • Carboplatin — DRUG
  • Olaparib — DRUG
  • Irinotecan — DRUG
  • Vistusertib — DRUG
  • Nivolumab — DRUG
  • Cyclophosphamide — DRUG
  • Selumetinib — DRUG
  • Enasidenib — DRUG
  • Lirilumab — DRUG
  • Fadraciclib — DRUG
  • Cytarabine — DRUG
  • Dexamethasone — DRUG
  • Ceralasertib — DRUG
  • Futibatinib — DRUG
  • Capmatinib — DRUG
  • Avelumab — DRUG
  • Peposertib — DRUG
  • Capivasertib — DRUG
  • Vinorelbine — DRUG

Study Details

This proof-of-concept platform trial is designed to cover the targeting of several survival pathways in oncogenesis that are currently not adequately employed for pediatric patients in Europe (Geoerger 2017; Geoerger 2019). The aims of the trial are: 1. To determine the recommended phase II dose (RP2D) of a specific anticancer agent and/or a relevant combination in a pediatric population, to document its tolerability and 2. To explore first signals of activity in a molecularly enriched study population.

Key Dates

Start date
Aug 3, 2016
Status verified
Jan 2026
Primary completion
Feb 28, 2031
Completion
Feb 28, 2031

Study Design

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

Arms

  • Experimental: Arm A. Ribociclib + Topotecan and Temozolomide
    Topotecan iv QD and temozolomide capsules orally QD Days 1 to 5; Ribociclib capsules or oral solution orally QD from Day 6 to 20 of a 28 day cycle.
  • Experimental: Arm B. Ribociclib + Everolimus
    Ribociclib capsules or oral solution orally QD for 21 days of each 28 day cycle; Everolimus orodispersible tablets orally QD for 28 days.
  • Experimental: ARM C. Adavosertib + Carboplatin
    Adavosertib capsules orally BID 3 days on / 4 days off in week 1; Carboplatin iv QD AUC 5 on Day 1 of a 21 day cycle.
  • Experimental: Arm D. Olaparib + Irinotecan
    Olaparib tablets orally BID on Day 1-10 of a 21 day cycle Irinotecan iv QD on Day 4-8 of a 21 day cycle.
  • Experimental: Arm E. Vistusertib single agent
    Vistusertib tablets orally BID 2 days on/5 days off per week of a 28 day cycle.
  • Experimental: Arm F. Vistusertib + Topotecan and Temozolomide
    Topotecan iv QD and temozolomide capsules orally QD Days 1 to 5; Vistusertib tablets orally BID 3 days on/4 days off per week of a 28 day cycle.
  • Experimental: Arm G. Nivolumab + Cyclophosphamide +/- Radiotherapy
    Nivolumab iv QD every 2 weeks of a 28 day cycle (Days 1 and 15); Cyclophosphamide tablets or oral solution orally BID, 1 week on/1 week off; Palliative irradiation/radiofrequency/cryotherapy starting 2 weeks after the first nivolumab injection.
  • Experimental: Arm H. Selumetinib + Vistusertib
    Selumetinib capsules twice daily on a continous administration. Vistusertib orally twice daily on an intermittent schedule : 2 days on / 5 days off per week of a 28 day cycle.
  • Experimental: Arm I. Enasidenib
    Enasidenib tablets or sprinkle solution orally on a continuous dosing once daily (QD) per 28 day cycle.
  • Experimental: Arm J. Lirilumab + Nivolumab
    Nivolumab iv QD on Day 1 and 15 of a 28 day cycle; Lirilumab iv QD on Day 1 of a 28 day cycle
  • Experimental: Arm K. Fadraciclib (CYC065) + Temozolomide
    Fadraciclib iv QD on Day 1 (+/- 15) of a 28 day cycle Temozolomide capsules orally QD on Day 1-5 of a 28 day cycle
  • Experimental: Arm L. Fadraciclib (CYC065) + Cytarabine
    Fadraciclib iv QD on Day 1 (+/- 15) of a 28 day cycle Cytarabine iv or sc on Day 2-5 and Day 8-11 of a 28 day cycle
  • Experimental: Arm M. Ribociclib + Everolimus +/- Dexamethasone
    Ribociclib capsules or tablets orally QD on Day 1-21 of a 28 day cycle. Everolimus dispersible tablets orally QD on a continuous dosing per 28 day cycle. For patients with leukemia and lymphoma: Dexamethasone orally or iv on Day 1-7 of each 28 day cycle. For patients with ALL, AML and Non-Hodgkin Lymphoma (NHL), Intrathecal chemotherapy will be administered additionally as per standard practice depending on CNS status.
  • Experimental: Arm N. Ceralasertib (AZD6738) + Olaparib
    Olaparib tablets orally BID per 28 days Ceralasertib tablets QD or BID per 28 day cycle
  • Experimental: Arm O. Futibatinib (TAS-120)
    Futibatinib tablets orally on a continuous dosing QD per 28 day cycle
  • Experimental: Arm P. Capmatinib (INC280) + Everolimus
    Capmatinib tablets orally on a continuous dosing BID per 28 day cycle. Everolimus dispersible tablets orally QD on a continuous dosing per 28 day cycle.
  • Experimental: Arm Q. Peposertib + Avelumab and Metronomic Temozolomide
    Peposertib tablets orally on a continuous dosing BID per 28 day cycle Avelumab IV QD on Day 1 and Day 15 of a 28 day cycle Temozolomide capsules orally QD 5 days/week of a 28 day cycle
  • Experimental: Arm R. Capivasertib + metronomic Vinorelbine
    Capivasertib tablets orally BID on Day 1-4/week (4 days on/3 days off, every week) of a 28 day cycle. Vinorelbine soft capsules orally once daily on Day 1, 3 and 5/week of a 28 day cycle.

Primary Outcome Measure

Recommended phase II dose (RP2D) [ Time Frame: During the first cycle ]

Central Contacts

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