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Combining Ribociclib with Topotecan and Temozolomide for Pediatric Cancer

Phase I/II Multicenter Study to Assess Efficacy and Safety of Ribociclib (LEE011) in Combination With Topotecan and Temozolomide (TOTEM) in Pediatric Patients With Relapsed or Refractory Neuroblastoma and Other Solid Tumors

Phase1; Phase2 Interventional Novartis · NCT05429502

This study is testing a new combination of three drugs to see if it can help children with tough-to-treat cancers like neuroblastoma feel better and improve their chances of recovery.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment231 (estimated)
Ages12 Months to 21 Years
SexAll
SponsorNovartis Industry-sponsored
Drugs / interventionsradiation
Locations13 sites (Boston, Massachusetts and 12 other locations)
Trial IDNCT05429502 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and effectiveness of ribociclib when used alongside topotecan and temozolomide in children with relapsed or refractory neuroblastoma and other solid tumors. It consists of a Phase I dose-finding part to determine the maximum tolerated dose, followed by multiple expansion cohorts to assess the treatment's preliminary antitumor activity. If successful, a Phase II randomized, double-blind, placebo-controlled trial will be conducted to further evaluate the treatment in pediatric patients. The study aims to provide a new therapeutic option for young patients facing aggressive cancers.

Who should consider this trial

Good fit: Ideal candidates are children aged 12 months to 21 years with relapsed or refractory neuroblastoma or other specified solid tumors.

Not a fit: Patients with solid tumors that have not progressed despite standard therapy or those with bone marrow-only disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new hope for pediatric patients with difficult-to-treat cancers.

How similar studies have performed: Other studies have shown promise in using similar combinations of therapies for pediatric cancers, suggesting potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Participants and/or guardian have the ability to understand and the willingness to sign a written informed consent document.
2. Age ≥ 12 months and ≤ 21 years at the time of signing consent form Note: The first dose level of Phase I - part A (dose finding) will enroll participants ≥ 12 years - 21 years old, and may expand to younger participants (≥ 12 months to \< 12 years) as determined by the data.
3. Histologically or cytologically confirmed solid tumors listed below that have progressed despite standard therapy or for which no effective standard therapy exists.

   1. Neuroblastoma (for Phase I and Phase II): Histologically proven neuroblastoma as per International Neuroblastoma Staging System (INSS); Relapsed or refractory disease; Measurable disease per International Neuroblastoma Response criteria (INRC); Bone marrow only disease not eligible; Available MYCN status before screening
   2. Medulloblastoma (for Phase I) regardless of genetic status (i.e. Groups 3 or 4 WNT-activated or non-WNT, SHH-activated or non-SHH)
   3. High-grade glioma (for Phase I): including HGG NOS, WHO Grade III or Grade IV; Glioblastoma, IDH-wildtype or IDH-mutant; Anaplastic astrocytoma, IDH-mutant; Anaplastic oligodendroglioma, IDH-mutant; Anaplastic pleomorphic xanthoastrocytoma; Diffuse midline gliomas, H3 K27-altered; Diffuse hemispheric glioma, H3 G34-mutant; Diffuse pediatric-type HGG, H3-wildtype and IDH-wildtype.
   4. Malignant rhabdoid tumor (for Phase I) includes diagnoses of atypical teratoid/rhabdoid tumor (AT/RT), and rhabdoid tumor of the kidney (RTK), and other soft tissues as defined by 2 of the 3 following criteria; either (1)+(2) or (1)+(3): (1) Morphology and immunophenotypic panel consistent with rhabdoid tumor; (2) Loss of SMARCB1 confirmed by immunohistochemistry; (3) Molecular confirmation of tumor-specific bi-allelic SMARCB1 loss/mutation is encouraged in cases where SMARCB1 immunohistochemistry is equivocal, and required if SMARCB1 immunohistochemistry is not available
   5. Rhabdomyosarcoma (for Phase I) independent of fusion status and subtype
4. Participants with CNS disease who are on corticosteroids should take stable doses for at least 7 days prior to first dose of ribociclib with no plans for escalation.
5. Performance status:

   1. ≤ 16 years: Lansky Play score ≥ 50%
   2. \>16 years: Karnofsky performance status ≥ 50% or ECOG \< 3
6. Life expectancy of ≥ 12 weeks at the time of enrollment
7. Adequate bone marrow function (bone marrow may be involved with tumor) and organ function
8. Adequate hepatic, renal, cardiac function
9. Females who are sexually active must agree to use highly effective contraception during and for 6 months after treatment. Additionally, females of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose of study medication. Pregnant or lactating females are not eligible for the study.
10. Sexually active males (including those that have had a vasectomy), who do not agree to abstinence, must be willing to use a condom during intercourse while on study treatment and for 6 months after stopping treatment.

Exclusion Criteria:

1. Known hypersensitivity to any of the excipients of ribociclib or topotecan or temozolomide.
2. Not recovered from clinical and laboratory acute toxicities related to prior anti-cancer therapies
3. Concurrent severe and/or uncontrolled concurrent medical conditions (serious infections or significant cardiac, pulmonary, hepatic, psychiatric, GI disease, or other organ dysfunction) that in the investigator's judgement could compromise their ability to tolerate or absorb protocol therapy or would interfere with the study procedures or results
4. Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality
5. History of QTc prolongation; taking medications with a known risk to prolong the QT interval hat cannot be discontinued or replaced by safe alternative medication
6. Currently taking medications that are mainly metabolized by CYP3A4/5 with a narrow therapeutic index, strong inducers or inhibitors of CYP3A4/5, herbal preparations/medications and dietary supplements
7. Vaccinated with live, attenuated vaccines within 4 weeks
8. Participated in a prior investigational study within 30 days
9. Received prior treatment with a CDK4/6 inhibitor
10. Received last dose of anticancer therapy (including experimental) within 4 weeks
11. Previous myeloablative therapy with autologous hematopoietic stem cell rescue within 8 weeks
12. Allogeneic stem cell transplant within 3 months
13. Has last fraction of radiation within 4 weeks
14. Major surgery within 2 weeks
15. Pregnant or nursing (breast feeding) female participant or female participant who plans to become pregnant or breast-feed during the trial.

Other protocol-defined inclusion/exclusion criteria may apply

Where this trial is running

Boston, Massachusetts and 12 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Neuroblastomaneuroblastomamedulloblastomahigh-grade gliomamalignant rhabdoid tumorsrhabdomyosarcomarelapsedrefractory
Last reviewed 2026-06-10 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.