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Study to assess safety and identify dose of ribociclib in combination of temozolomide and topotecan (TOTEM) in patients (12 months – 21 years old) with relapsed or refractory solid tumors (Phase I), and further assess efficacy and safety in patients (12 months – 21 years old) with relapsed or refractory neuroblastoma (Phase II)
EU CTIS ID: 2024-512095-35-00
What this study is testing
Phase I - part A: To determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of ribociclib in combination with TOTEM. Phase I - part B: To evaluate antitumor activity as assessed by Overall Response Rate (ORR) of ribociclib in combination with TOTEM. Phase II: To evaluate the treatment effect as assessed by ORR of ribociclib in combination with TOTEM versus placebo plus TOTEM.
- Phase I and Phase II (Integrated)- Other
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Signed informed consent/assent must be obtained prior to participation in the study. Participants and/or guardian must have the ability to understand and the willingness to sign a written informed consent document.
- Age ≥ 12 months and ≤ 21 years at the time of signing consent form.
- Histologically or cytologically confirmed solid tumors listed below that have progressed despite standard therapy or for which no effective standard therapy exists. a. Neuroblastoma (NB) (Phase I and Phase II) b. Medulloblastoma (MB) (Phase I) regardless of genetic status (i.e. Groups 3 or 4 WNT-activated or non-WNT, SHH-activated or non-SHH). c. High-grade glioma (HGG) (Phase I): Note: excluding any low grades (grade I or grade II) such as astrocytoma, oligodendroglioma, or mixed glioneuronal tumors d. Malignant rhabdoid tumor (MRT) (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 (i)+(ii) or (i)+(iii): e. Rhabdomyosarcoma (RMS) (Phase I) independent of fusion status and subtype.
- Participants with central nervous system (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. Note: participants with symptomatic CNS disease who are neurologically unstable or require local CNS-directed therapy to control their CNS disease are not eligible for the study
- Measurable disease per Revised Assessment in Neuro-Oncology (RANO) criteria for participants with HGG and per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for MB, MRT and RMS.
- Performance status: participants who are unable to walk because of paralysis, but who are able to sit upright unassisted in a wheelchair, will be considered ambulatory for the purpose of assessing performance score
You likely can't join if
- Known hypersensitivity to any of the excipients of ribociclib or topotecan or temozolomide.
- Participated in a investigational study within 30 days or 5 half-lives
- Received prior treatment with a CDK4/6 inhibitor
- Received anticancer therapy (including experimental) within 4 weeks
- Received myeloablative therapy with autologous hematopoietic stem cell rescue within 8 weeks
- Received allogeneic stem cell transplant within 3 months
See the full eligibility criteria
Who can join
- Signed informed consent/assent must be obtained prior to participation in the study. Participants and/or guardian must have the ability to understand and the willingness to sign a written informed consent document.
- Age ≥ 12 months and ≤ 21 years at the time of signing consent form.
- Histologically or cytologically confirmed solid tumors listed below that have progressed despite standard therapy or for which no effective standard therapy exists. a. Neuroblastoma (NB) (Phase I and Phase II) b. Medulloblastoma (MB) (Phase I) regardless of genetic status (i.e. Groups 3 or 4 WNT-activated or non-WNT, SHH-activated or non-SHH). c. High-grade glioma (HGG) (Phase I): Note: excluding any low grades (grade I or grade II) such as astrocytoma, oligodendroglioma, or mixed glioneuronal tumors d. Malignant rhabdoid tumor (MRT) (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 (i)+(ii) or (i)+(iii): e. Rhabdomyosarcoma (RMS) (Phase I) independent of fusion status and subtype.
- Participants with central nervous system (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. Note: participants with symptomatic CNS disease who are neurologically unstable or require local CNS-directed therapy to control their CNS disease are not eligible for the study
- Measurable disease per Revised Assessment in Neuro-Oncology (RANO) criteria for participants with HGG and per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for MB, MRT and RMS.
- Performance status: participants who are unable to walk because of paralysis, but who are able to sit upright unassisted in a wheelchair, will be considered ambulatory for the purpose of assessing performance score
- Life expectancy of ≥ 12 weeks at the time of enrollment.
- Adequate bone marrow function (bone marrow may be involved with tumor) and organ function defined as: a. Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3 without growth factor support within 7 days of the test b. Platelet count ≥ 75,000/mm3 without support within 7 days of the test c. Hemoglobin ≥ 8.0 g/dL (transfusion allowed) d. Total bilirubin ≤ 1.5 x ULN for age (in case of Gilbert's syndrome, ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN for age) e. Adequate liver function, defined as total serum bilirubin ≤ 1.5 x ULN AND alanine aminotransferase (ALT) / aspartate aminotransferase (AST) ≤ 2.5 x ULN (in case of liver metastases, AST / ALT ≤ 5 x ULN) f. Adequate renal function, defined as serum creatinine ≤ 1.5 x ULN based on age/gender normal. In participants with serum creatinine > 1.5 x ULN for age/gender normal, a calculated glomerular filtration rate (GFR) must be ≥ 60 mL/min/1.73 m2. g. Adequate cardiac function, defined as corrected QTc interval using Fridericia's correction (QTcF) ≤ 450 ms and shortening fraction (SF) > 29% (> 35% for participants < 3 years) and left ventricular ejection fraction (LVEF) ≥ 50% on echocardiogram h. The following laboratory values within normal limits or corrected to within normal limits with supplements before first dose of study medication: Potassium; Magnesium; Total calcium (corrected for serum albumin)
What rules you out
- Known hypersensitivity to any of the excipients of ribociclib or topotecan or temozolomide.
- Participated in a investigational study within 30 days or 5 half-lives
- Received prior treatment with a CDK4/6 inhibitor
- Received anticancer therapy (including experimental) within 4 weeks
- Received myeloablative therapy with autologous hematopoietic stem cell rescue within 8 weeks
- Received allogeneic stem cell transplant within 3 months
- Has radiation within 4 weeks (or 2 weeks if radiation therapy is given for palliation), or within 6 weeks of MIBG treatment
- Major surgery within 2 weeks and not recovered fully from the side effects
- Not recovered from clinical and laboratory acute toxicities related to prior anti-cancer therapies
- Concurrent severe and/or uncontrolled concurrent medical conditions 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
- Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality
- History of QTcF prolongation (i.e. QTcF interval of > 450 ms) or QTcF > 450 ms on screening ECG
- Currently taking medications with a known risk to prolong the QT interval or induce TdP that cannot be discontinued or replaced by safe alternative medication
- Currently taking medications that are known strong inducers or inhibitors of CYP3A4/5 cannot be discontinued at least 7 days or 5 halflives
- Currently taking medications that are mainly metabolized by CYP3A4/5 with a narrow therapeutic index that cannot be discontinued at least 7 days or 5 half-lives
- Vaccinated with live, attenuated vaccines within 4 weeks
The study team makes the final eligibility decision.
Where it's taking place
- Canada
- Singapore
- Taiwan
- Korea, Republic of
- Argentina
- Australia
- United Kingdom
- United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 0-17 years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Canada; Singapore; Taiwan; Korea, Republic of; Argentina; Australia and 2 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.