Clinical Trial: NCT02780128 - My Cancer Genome

NCT02780128

Description:

The purpose of this research study is to match genomic aberrations in tumor cells at time of relapse to rationally designed combinations of molecularly targeted agents. This study will be done in two parts: Part I: Tumor will be accessed at study entry via a biopsy and subjected to deep sequencing to identify protocol-specified biomarkers for therapy assignment. Part II: If the tumor contains a genetic change defined by the study as being actionable, and other criteria are met, participants will be assigned to therapy based upon the genetic changes identified in the tumor biopsy.

Related Conditions:

Neuroblastoma

Recruiting Status:

Recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT02780128

Trial Eligibility

Document

Title

Brief Title: Next Generation Personalized Neuroblastoma Therapy
Official Title: Next Generation Personalized Neuroblastoma Therapy (The NEPENTHE Trial)

Clinical Trial IDs

ORG STUDY ID: 14-011071
NCT ID: NCT02780128

Conditions

Neuroblastoma
Cancer

Interventions

Drug	Synonyms	Arms
Ribociclib	LEE011	Group 1: ALK
Ceritinib	LDK378	Group 1: ALK

Purpose

Trial Arms

Name	Type	Description	Interventions
Molecular Analysis	Other	All participants with relapsed or refractory neuroblastoma will have a tumor biopsy to identify genetic mutations. There is no drug given in this arm of the trial.
Group 1: ALK	Experimental	Qualified participants whose tumors show certain mutations in the anaplastic lymphoma kinase (ALK) pathway (based on genetic sequencing results) will receive a combination therapy of ceritinib and ribociclib, to be administered orally in 28-day cycles. Two different doses of ceritinib and three different doses of ribociclib will be evaluated. Once the investigators have identified the highest safe dose of both drugs that can be given at the same time, additional participants will be enrolled in the study at this dose level. It is possible that if starting at a lower dose, participants may take a higher dose once that dose has been deemed safe.	Ribociclib Ceritinib

Eligibility Criteria

        Inclusion Criteria:

          -  Aged ≥1 years to ≤ 21 years

          -  Relapsed or refractory neuroblastoma

          -  A sufficient interval between the last dose of prior anti-cancer therapy (including
             cytotoxic and biological therapies) and enrollment in this study, to allow recovery
             from the acute toxic effects of all prior anti-cancer therapy. Please contact site for
             specific details

          -  Adequate bone marrow function (bone marrow may be involved with tumor. Contact site
             for specific details)

          -  Adequate renal function, defined as Creatinine clearance or radioisotope glomerular
             filtration rate (GFR) ≥ 70 mL/min/1.73 m2 OR serum creatinine based on age/gender
             normal (contact site for details)

          -  Adequate liver function, defined as total serum bilirubin ≤ 1.5 times the upper limit
             of normal AND alanine transaminase (ALT) ≤ 110 U/L.

          -  Adequate cardiac function, defined as corrected QT interval (QTc) ≤ 480 msec AND
             shortening fraction > 27%

          -  Males and females who are sexually active must agree to use effective contraception
             during and for 3 months after treatment

        Exclusion Criteria:

          -  Subjects taking certain drugs or herbal medications that impact drug metabolism and/or
             cardiac function that cannot be discontinued (contact site for details).

          -  Subjects with concurrent severe and/or uncontrolled concurrent medical conditions that
             could compromise participation in the study (contact site for details)

          -  Other concomitant therapies:

          -  Corticosteroids initiated for tumor therapy within 7 days prior to study enrollment

          -  Other anti-cancer agents

          -  Other investigational drugs

          -  Hematological growth factors

          -  Radiation therapy

          -  Subjects < 0.5m2

          -  Pregnant or lactating females

          -  Sexually active males unless they use a condom during intercourse while taking study
             drug/s and for 3 months after study drug discontinuation and thus do not attempt to
             father a child in this period.

Maximum Eligible Age:	21 Years
Minimum Eligible Age:	1 Year
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Incidence of dose limiting toxicities when combining ceritinib with ribociclib
Time Frame:	At the end of Cycle 1 (each cycle is 28 days)
Safety Issue:
Description:	The primary variable is the incidence of dose limiting toxicities (DLTs) during the first 28 days of therapy

Secondary Outcome Measures

Measure:	Cataloguing of genomic alterations identified from biopsies performed at time of relapse in patients with relapsed or refractory neuroblastoma
Time Frame:	3 years
Safety Issue:
Description:	Neuroblastomas undergo substantial mutational evolution during therapy, and relapsed disease is more likely to be driven by a targetable oncogenic pathway. Genomic alterations measured by next-generation sequencing at time of disease progression will be characterized and reported in a descriptive manner.

Details

Phase:	Phase 1
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	Yael P Mosse

Trial Keywords

neuroblastoma
cancer
genetic profiling
ceritinib
ribociclib
NEPENTHE

Last Updated

August 19, 2021

Clinical Trials /

Next Generation Personalized Neuroblastoma Therapy