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NeuroblastomaPhase 1NEPENTHENCT02780128

Next Generation Personalized Neuroblastoma Therapy

A Phase 1 study testing Biopsy, Next Generation Sequencing and Tumor Scans in people with Neuroblastoma and Cancer, run by Yael P Mosse at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 1 year to 21 years
Conditions the study is for
Neuroblastoma, Cancer
What is being tested?
Biopsy, Next Generation Sequencing and Tumor Scans
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
1 siteUnited States
Study dates
Jul 2016to Aug 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • The Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

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

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.

Being tested
Biopsy, Next Generation Sequencing, Tumor Scans, Bone marrow Tests, Physical Exam
Keywords
neuroblastoma, cancer, genetic profiling, ceritinib, ribociclib, NEPENTHE
Medical subject headings
Neuroblastoma, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BiopsyProcedure or surgery

    Also called Genetic Sequencing

    Needle or incisional tumor biopsy

  • Next Generation SequencingGenetic

    Also called Molecular Profiling, Genetic Sequencing

    Tumor tissue will be sent to Foundation Medicine laboratory for molecular profiling.

  • Tumor ScansProcedure or surgery

    Participants will undergo different types of scans to look at your tumor. These scans include CT (computerized tomography), MIBG (meta-iodobenzylguanidine) PET (positron emission tomography), and MRI (magnetic resonance imaging). Participants may have more than one type of scan.

  • Bone marrow TestsProcedure or surgery

    Also called Bone marrow aspiration

    Participants will have needles inserted through their hip bone to remove fluid from inside the bone marrow. This test determines if participants have tumor in the bone marrow.

  • Physical ExamOther

    The exam includes taking participant weight, height, blood pressure, heart rate and respiratory rate and performing a examination of the participants body. The investigators may also check the participants vision with an eye chart.

  • Eye ExamOther

    Also called Ophthalmic Exam

    Participants will have their eyes will be evaluated using different instruments. Participants will also be asked to read an eye chart. The exams will take about 15 minutes.

  • LabsOther

    Also called Blood tests

    Standard blood tests will be done to measure different types of blood cells, to measure the amount of certain substances, and tests to check how well liver and kidneys are working. When possible, the investigators will take blood from the participants central line. If this is not possible, the investigators will take blood from a vein in the participants arm. First, the investigators will put some cream on the skin so that drawing blood will not be painful. Then the investigators will put a thin needle into the vein to draw the blood.

  • Pregnancy TestOther

    If the participant is 11 years old or older or has already started having periods, the participant will be asked to take a pregnancy test before starting this study. The results will be shared with the participant but not with the participants' parent(s). We strongly encourage the participant to share the results with the parents. If the participant is found to be pregnant, the participant will not be able to continue participation in the study. About 1 teaspoon of blood (or urine if a urine test) will be needed.

  • InterviewsBehavioural

    A team member will take the participant's medical history, along with a listing of any medications that are being taken. Throughout the study, participants will be asked to report if they think that anything bad has happened as a result of the study.

  • ECGOther

    Also called EKG, Electrocardiogram

    This is a test of electrical activity of the heart. The investigators will put electrodes (sticky pads attached to wires) on the participant's chest, arms and legs. The electrocardiogram (ECG) will not be uncomfortable, but the participant will have to lie still. It does not hurt and takes about 15 minutes.

  • EchocardiogramOther

    Also called ECHO

    The participant will have an Echocardiogram (ECHO), an ultrasound of the heart, taken to assess heart function. The investigators will put some gel on the skin and use a machine to take pictures of the heart.

  • RibociclibDrug

    Also called LEE011

    Participants will take ribociclib once per day orally for Days 1-21 of a 28-day cycle.

  • CeritinibDrug

    Also called LDK378

    Participants will take ceritinib once per day orally for 28 days of a 28-day cycle.

Study groups in NCT02780128
Study groupRoleWhat they receive
Molecular AnalysisOtherAll 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.
Receives: Procedure: Biopsy; Genetic: Next Generation Sequencing; Procedure: Tumor Scans; Other: Physical Exam; Other: Labs; Other: Pregnancy Test; Behavioral: Interviews
Group 1: ALKExperimentalQualified 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.
Receives: Procedure: Tumor Scans; Procedure: Bone marrow Tests; Other: Physical Exam; Other: Eye Exam; Other: Labs; Other: Pregnancy Test; Behavioral: Interviews; Other: ECG; Other: Echocardiogram; Drug: Ribociclib; Drug: Ceritinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of dose limiting toxicities when combining ceritinib with ribociclib

    The primary variable is the incidence of dose limiting toxicities (DLTs) during the first 28 days of therapy

    Measured: At the end of Cycle 1 (each cycle is 28 days)

  2. Area under the curve from time zero to last quantifiable concentration

    Area under the plasma concentration time-curve from zero to the last measured concentration

    Measured: At the end of Cycle 1 (each cycle is 28 days)

  3. Percentage of patients with overall objective response

    To describe whether the assigned targeted therapy can mediate anti-tumor effects in subjects with relapsed or refractory high-risk neuroblastoma within the context of a phase 1/phase1b biomarker-driven trial. Percentage of patients with objective response will be according to the International Neuroblastoma Response Criteria.

    Measured: 2 years

Secondary outcomes (1)

  1. Cataloguing of genomic alterations identified from biopsies performed at time of relapse in patients with relapsed or refractory neuroblastoma

    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.

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 May 2016 (estimated)
  2. Study startJul 2016
  3. Primary completionAug 2022
  4. Study completionAug 2022

Why it stopped: The goals of Part 1 (molecular screening) were met, but lack of therapies to match molecular aberrations made Part 2 (treatment) no longer feasible.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
66 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02780128
Sponsor's protocol ID
14-011071
Acronym
NEPENTHE
Status last verified
Mar 2026
First submitted
11 May 2016
Last updated
10 Mar 2026
Results posted
No
Data monitoring committee
Yes

Publications

  • Rader 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.

    PubMed 24045179

  • Bresler 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.

    PubMed 25517749

  • Bresler 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.

    PubMed 22072639

  • Carr-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.

    PubMed 20145180

  • Geoerger 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.

    PubMed 28432176

  • Hart LS, Rader J, Raman P, Batra V, Russell MR, Tsang M, Gagliardi M, Chen L, Martinez D, Li Y, Wood A, Kim S, Parasuraman S, Delach S, Cole KA, Krupa S, Boehm M, Peters M, Caponigro G, Maris JM. Preclinical Therapeutic Synergy of MEK1/2 and CDK4/6 Inhibition in Neuroblastoma. Clin Cancer Res. 2017 Apr 1;23(7):1785-1796. doi: 10.1158/1078-0432.CCR-16-1131. Epub 2016 Oct 11.

    PubMed 27729458

  • Mosse YP, Laudenslager M, Longo L, Cole KA, Wood A, Attiyeh EF, Laquaglia MJ, Sennett R, Lynch JE, Perri P, Laureys G, Speleman F, Kim C, Hou C, Hakonarson H, Torkamani A, Schork NJ, Brodeur GM, Tonini GP, Rappaport E, Devoto M, Maris JM. Identification of ALK as a major familial neuroblastoma predisposition gene. Nature. 2008 Oct 16;455(7215):930-5. doi: 10.1038/nature07261. Epub 2008 Aug 24.

    PubMed 18724359

  • Mosse YP, Lim MS, Voss SD, Wilner K, Ruffner K, Laliberte J, Rolland D, Balis FM, Maris JM, Weigel BJ, Ingle AM, Ahern C, Adamson PC, Blaney SM. Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children's Oncology Group phase 1 consortium study. Lancet Oncol. 2013 May;14(6):472-80. doi: 10.1016/S1470-2045(13)70095-0. Epub 2013 Apr 16.

    PubMed 23598171

  • Mosse YP, Voss SD, Lim MS, Rolland D, Minard CG, Fox E, Adamson P, Wilner K, Blaney SM, Weigel BJ. Targeting ALK With Crizotinib in Pediatric Anaplastic Large Cell Lymphoma and Inflammatory Myofibroblastic Tumor: A Children's Oncology Group Study. J Clin Oncol. 2017 Oct 1;35(28):3215-3221. doi: 10.1200/JCO.2017.73.4830. Epub 2017 Aug 8.

    PubMed 28787259

  • Padovan-Merhar OM, Raman P, Ostrovnaya I, Kalletla K, Rubnitz KR, Sanford EM, Ali SM, Miller VA, Mosse YP, Granger MP, Weiss B, Maris JM, Modak S. Enrichment of Targetable Mutations in the Relapsed Neuroblastoma Genome. PLoS Genet. 2016 Dec 20;12(12):e1006501. doi: 10.1371/journal.pgen.1006501. eCollection 2016 Dec.

    PubMed 27997549

  • Rihani A, Vandesompele J, Speleman F, Van Maerken T. Inhibition of CDK4/6 as a novel therapeutic option for neuroblastoma. Cancer Cell Int. 2015 Jul 30;15:76. doi: 10.1186/s12935-015-0224-y. eCollection 2015.

    PubMed 26225123

  • Van Maerken T, Rihani A, Dreidax D, De Clercq S, Yigit N, Marine JC, Westermann F, De Paepe A, Vandesompele J, Speleman F. Functional analysis of the p53 pathway in neuroblastoma cells using the small-molecule MDM2 antagonist nutlin-3. Mol Cancer Ther. 2011 Jun;10(6):983-93. doi: 10.1158/1535-7163.MCT-10-1090. Epub 2011 Apr 1.

    PubMed 21460101

  • Van Maerken T, Vandesompele J, Rihani A, De Paepe A, Speleman F. Escape from p53-mediated tumor surveillance in neuroblastoma: switching off the p14(ARF)-MDM2-p53 axis. Cell Death Differ. 2009 Dec;16(12):1563-72. doi: 10.1038/cdd.2009.138. Epub 2009 Sep 25.

    PubMed 19779493

  • Wood AC, Krytska K, Ryles HT, Infarinato NR, Sano R, Hansel TD, Hart LS, King FJ, Smith TR, Ainscow E, Grandinetti KB, Tuntland T, Kim S, Caponigro G, He YQ, Krupa S, Li N, Harris JL, Mosse YP. Dual ALK and CDK4/6 Inhibition Demonstrates Synergy against Neuroblastoma. Clin Cancer Res. 2017 Jun 1;23(11):2856-2868. doi: 10.1158/1078-0432.CCR-16-1114. Epub 2016 Dec 16.

    PubMed 27986745

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Biopsy, Next Generation Sequencing and Tumor Scans in people with Neuroblastoma and Cancer, run by Yael P Mosse at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 10 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The goals of Part 1 (molecular screening) were met, but lack of therapies to match molecular aberrations made Part 2 (treatment) no longer feasible.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose limiting toxicities when combining ceritinib with ribociclib (time frame: At the end of Cycle 1 (each cycle is 28 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02780128, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2026.

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Next Generation Personalized Neuroblastoma Therapy | AzTrials