Clinical trial · Interventional
Next Generation Personalized Neuroblastoma Therapy
Next Generation Personalized Neuroblastoma Therapy (The NEPENTHE Trial)
NCT02780128CI-TRIAL-00105132NEPENTHEterminatedPhase 1ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Why stopped (as posted): The goals of Part 1 (molecular screening) were met, but lack of therapies to match molecular aberrations made Part 2 (treatment) no longer feasible.
Summary
Brief summary (as posted)
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.
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Cancer | Malignant Neoplasm | ALIAS | 0.90 |
| Neuroblastoma | Neuroblastoma | ONTOLOGY_EXACT | 0.90 |
Interventions
Interventions (13)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Biopsy | Procedure | — | UNRESOLVED |
| Bone marrow Tests | Procedure | — | UNRESOLVED |
| Ceritinib | Drug | Ceritinib | ALIAS |
| ECG | Other | — | UNRESOLVED |
| Echocardiogram | Other | — | UNRESOLVED |
| Eye Exam | Other | — | UNRESOLVED |
| Interviews | Behavioral | — | UNRESOLVED |
| Labs | Other | — | UNRESOLVED |
| Next Generation Sequencing | Genetic | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- OTHER
- label
- Molecular Analysis
- description
- 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.
- interventionNames
- Procedure: Biopsy
- Genetic: Next Generation Sequencing
- Procedure: Tumor Scans
- Other: Physical Exam
- Other: Labs
- Other: Pregnancy Test
- Behavioral: Interviews
- type
- EXPERIMENTAL
- label
- Group 1: ALK
- description
- 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.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 1 Year
- Maximum age
- 21 Years
Show eligibility criteria text
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.
References
Publications (14)
- BACKGROUNDRader J, Russell MR, Hart LS, Nakazawa MS, Belcastro LT, Martinez D, Li Y, Carpenter EL, Attiyeh EF, Diskin SJ, Kim S, Parasuraman S, Caponigro G, Schnepp RW, Wood AC, Pawel B, Cole KA, Maris JM. Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(22):6173-82. doi: 10.1158/1078-0432.CCR-13-1675. Epub 2013 Sep 17. PMID 24045179
- BACKGROUNDBresler SC, Weiser DA, Huwe PJ, Park JH, Krytska K, Ryles H, Laudenslager M, Rappaport EF, Wood AC, McGrady PW, Hogarty MD, London WB, Radhakrishnan R, Lemmon MA, Mosse YP. ALK mutations confer differential oncogenic activation and sensitivity to ALK inhibition therapy in neuroblastoma. Cancer Cell. 2014 Nov 10;26(5):682-94. doi: 10.1016/j.ccell.2014.09.019. Epub 2014 Nov 10. PMID 25517749
- BACKGROUNDBresler SC, Wood AC, Haglund EA, Courtright J, Belcastro LT, Plegaria JS, Cole K, Toporovskaya Y, Zhao H, Carpenter EL, Christensen JG, Maris JM, Lemmon MA, Mosse YP. Differential inhibitor sensitivity of anaplastic lymphoma kinase variants found in neuroblastoma. Sci Transl Med. 2011 Nov 9;3(108):108ra114. doi: 10.1126/scitranslmed.3002950. PMID 22072639
- BACKGROUNDCarr-Wilkinson J, O'Toole K, Wood KM, Challen CC, Baker AG, Board JR, Evans L, Cole M, Cheung NK, Boos J, Kohler G, Leuschner I, Pearson AD, Lunec J, Tweddle DA. High Frequency of p53/MDM2/p14ARF Pathway Abnormalities in Relapsed Neuroblastoma. Clin Cancer Res. 2010 Feb 15;16(4):1108-18. doi: 10.1158/1078-0432.CCR-09-1865. Epub 2010 Feb 9. PMID 20145180
- BACKGROUNDGeoerger B, Bourdeaut F, DuBois SG, Fischer M, Geller JI, Gottardo NG, Marabelle A, Pearson ADJ, Modak S, Cash T, Robinson GW, Motta M, Matano A, Bhansali SG, Dobson JR, Parasuraman S, Chi SN. A Phase I Study of the CDK4/6 Inhibitor Ribociclib (LEE011) in Pediatric Patients with Malignant Rhabdoid Tumors, Neuroblastoma, and Other Solid Tumors. Clin Cancer Res. 2017 May 15;23(10):2433-2441. doi: 10.1158/1078-0432.CCR-16-2898. Epub 2017 Apr 21. PMID 28432176