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A Study of Pembrolizumab (MK-3475) in Pediatric Participants With an AdvancedSolid Tumor or Lymphoma (MK-3475-051/KEYNOTE-051)

Studio Clinico

Patologia: Melanoma, Linfomi, Altre neoplasie

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Monocentrico

Randomizzato: No

Fase di studio: I, II

Richiesta mandatoria di tessuto: 

Linee di trattamento: Non applicabile

Criteri di inclusione: 

- Between 6 months and <18 years of age (or between 3 years and <18 years of age for rrcHL participants) on day of signing informed consent/assent (the first 3 participants dosed in Part 1 are to be ≥ 6 years of age)
- Histologically- or cytologically-documented, locally-advanced, or metastatic solid malignancy or lymphoma that is incurable and has failed prior standard therapy, or for which no standard therapy exists, or for which no standard therapy is considered appropriate
- Any number of prior treatment regimens
- Tissue (or lymph node biopsy for rrcHL participants) available from an archival tissue sample or, if appropriate, a newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
- Advanced melanoma or PD-L1-positive advanced, relapsed, or refractory solid tumor or lymphoma
- Measurable disease based on RECIST 1.1 (Or based on IWG [Cheson, 2007] [i.e., measurement must be >15 mm in longest diameter or >10 mm in short axis] for rrcHL participants)
- Participants with neuroblastoma with only metaiodobenzylguanidine (MIBG)-positive evaluable disease may be enrolled
- Lansky Play Scale ≥50 for participants from 6 months up to and including 16 years of age; or Karnofsky score ≥50 for participants >16 years of age
- Adequate organ function
- Female participants of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication
- Female participants of childbearing potential must be willing to use 2 methods of contraception or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication
- Male participants of reproductive potential must agree to use an adequate method of contraception starting with the first dose of study medication through 120 days after the last dose of study medication

Criteri di esclusione: 

- Has undergone major surgery including local prostate intervention (excluding prostate biopsy) within 28 days prior to randomization and not recovered adequately from the toxicities and/or complications

Schema di trattamento: 

Pembrolizumab 200mg IV

Trattamento sperimentale: 

Pembrolizumab

Trattamento di controllo: 

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Obiettivi primari dello studio: 

1) To determine the safety and tolerability of pembrolizumab based on AEs and clinical and laboratory measures in children with rrcHL.
2) To evaluate anti-tumor activity of pembrolizumab in the rrcHL Cohort based on the ORR per blinded independent central radiology assessment according to the International Working group (IWG) response criteria [1], based on assessments every 12 weeks.
Hypothesis: IV administration of pembrolizumab in the rrcHL Cohort will result in an ORR of greater than 10% using IWG response criteria [1] per blinded independent central radiology assessmen

Primary Objectives for the Relapsed Refractory Classical Hodgkin Lymphoma Cohort
Part II:
1) To determine the safety and tolerability of pembrolizumab based on AEs and clinical and laboratory measures in children with rrcHL.
2) To evaluate anti-tumor activity of pembrolizumab in the rrcHL Cohort
based on the ORR per blinded independent central radiology assessment according to the International Working group (IWG) response criteria [1], based on assessments every 12 weeks.
Hypothesis: IV administration of pembrolizumab in the rrcHL Cohort will result in an ORR of greater than 10% using IWG response criteria [1] per blinded independent central radiology assessment.

Obiettivi secondari dello studio: 

1) To evaluate clinical activity of pembrolizumab within each tumor type as measured by site assessment:
   • Duration of response (DOR), disease control rate (DCR) and progression-free survival (PFS) by RECIST 1.1
   • ORR, DOR, DCR, and PFS by irRECIST
   • Overall survival
2) To assess at least 5 out of the following markers NRAS, BRAF, MEK, KIT, PDGF, TP53, RB1 and BRCA1, Akt phosphorylation, IL-17 and PD-L1, in tissue samples at baseline and, in available tissue samples, at the time of progression.
3) To assess the change in vaccinated antibody concentrations, and memory B- and T-cell counts
4) To evaluate the relationship between baseline tumor PD-L1 expression and clinical efficacy outcomes.

Secondary Objectives for Relapsed Refractory Classical Hodgkin Lymphoma
Part I and Part II:
1) To evaluate anti-tumor activity of pembrolizumab in the rrcHL Cohort according to the International Working group (IWG) response criteria [1], based on assessments every 12 weeks by the following endpoints:
   • ORR, DOR and PFS per site assessment.
   • ORR, DOR and PFS per blinded independent central radiology assessment .
   • Overall survival.
2) To assess at least 5 out of the following markers NRAS, BRAF, MEK, KIT, PDGF, TP53, RB1 and BRCA1, Akt phosphorylation, IL-17 and PD-L1, in tissue samples at baseline and, in available tissue samples, at the time of progression.
3) To assess the change in vaccinated antibody concentrations, and memory B- and T-cell counts.
4) To assess PD-L1 and PD-L2 expression and other biomarkers to compare the extent of pre-pembrolizumab PD-L1 expression in tissue biopsies for pembrolizumab responders versus non-responders.

Note generali: 

Italy is involved only in Part II study
With Amendment 8, enrollment of participants with solid tumors and of participants aged 6 months to <12 years with melanoma were closed. Enrollment of participants aged ≥12 years to ≤18 years with melanoma continues. Enrollment of participants with MSI-H solid tumors and Classical Hodgkin Lymphoma continues.

Data di inizio dell'arruolamento: 14.03.2015

Data di fine dell'arruolamento: 18.04.2022

Centri partecipanti

Centro Italia

Ospedale Pediatrico Bambin Gesù
Piazza Sant Onofrio 4 - 00165 Roma - RM

Riferimento: Prof. Franco Locatelli
Telefono: 0668592129
Email: franco.locatelli@opbg.net

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2014-002950-38

Data di inserimento: 27.09.2017

Data di aggiornamento: 20.09.2019

Promotore

Merck Sharp & Dohme Corp.

CRO

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Principal Investigator ITALIA

Ospedale Pediatrico Bambino Gesù, Roma

Riferimento: Prof. Franco Locatelli

Telefono: 0668592129

Email: franco.locatelli@opbg.net

Localita: Roma

 

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