Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.
An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.
Searching Both is inclusive of interventional and observational studies.
|Eligible Ages||12 Months - 21 Years|
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.
- (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.
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 myeloblative 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. Other protocol-defined inclusion/exclusion criteria may apply
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.
Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.
Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.
Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
|Phase 1/Phase 2|
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.
The person who is responsible for the scientific and technical direction of the entire clinical study.
|Principal Investigator Affiliation||Novartis Pharmaceuticals|
Category of organization(s) involved as sponsor (and collaborator) supporting the trial.
The disease, disorder, syndrome, illness, or injury that is being studied.
The study consists of Phase I -part A (dose finding) and Phase I
- - part B (multiple expansion cohorts).
- I. - Phase I-Part A (dose finding): a dose finding to determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of ribociclib in combination with TOTEM.
- - Phase I- Part B (multiple expansion cohorts): it will be initiated to confirm RP2D identified from Phase I-part A.
- - Phase II- Double-blind, randomized, placebo controlled in r/r NB: It is a two-arm randomized, double blinded, placebo controlled, parallel group trial in participants with r/r NB.
Experimental: Phase I-part A: Ribociclib+TOTEM
Participants with r/r NB, MB, HGG, MRT or RMS will be treated with ribociclib in combination with TOTEM to determine MTD and/or RP2D. Ribociclib dose will be scalated while topotecan and temozolomide will be administered at a fixed dose.
Experimental: Phase I- Part B: r/r NB Cohort
Participants with r/r NB will be treated with ribociclib in combination with TOTEM at the PR2D identified from Phase I-Part A
Experimental: Phase I- Part B: r/r MB Cohort
Participants with r/r MB will be treated with ribociclib in combination with TOTEM at the PR2D identified from Phase I-Part A
Experimental: Phase I-Part B: r/r HGG Cohort
Participants with r/r HGG will be treated with ribociclib in combination with TOTEM at the PR2D identified from Phase I-Part A
Experimental: Phase I-Part B: r/r MRT Cohort
Participants with r/r MRT will be treated with ribociclib in combination with TOTEM at the PR2D identified from Phase I-Part A
Experimental: Phase I- Part B: r/r RMS Cohort
Participants with r/r RMS will be treated with ribociclib in combination with TOTEM at the PR2D identified from Phase I-Part A
Experimental: Phase II- Ribociclib+TOTEM
Participants with r/r NB will be treated with ribocilib in combination with TOTEM at the RP2D defined from Phase I part A.
Placebo Comparator: Phase II: Placebo+TOTEM
Participants with r/r NB will be treated ribociclib matching placebo in combination with TOTEM
Drug: - Topotecan
Topotecan administered at the standard dose given to neuroblastoma patients
Drug: - Temozolomide
Temozolamide administered at the standard dose given to neuroblastoma patients
Drug: - Ribociclib
Ribociclib administered at the RP2D defined from Phase I-Part A.
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.