Relapsed or refractory tumors in children
Conditions
Interventions
Product Name: Ribociclib
Product Code: LEE011
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: RIBOCICLIB
Current Sponsor code: LEE011
Concentration unit: mg milligram(s)
Concentration type: eq
Sponsors
Gustave Roussy
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must be diagnosed with a malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists. 2. Age 12 years of age) or Lansky Play score (for patients =12 years of age) = 70%. 7. Life expectancy = 3 months 8. Adequate organ function: 9. Able to comply with scheduled follow-up and with management of toxicity. 10. Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to initiation of treatment. 11. For all oral medications patients must be able to comfortably swallow capsules (except for those for which an oral solution is available; nasogastric or gastrostomy feeding tube administration is allowed only if indicated). 12. Written informed consent from parents/legal representative, patient, and age-appropriate assent before any study-specific screening procedures are conducted, according to local, regional or national guidelines. 13. Patient affiliated to a social security regimen or beneficiary of the same according to local requirements. Are the trial subjects under 18? yes Number of subjects for this age range: 285 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 4 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or require increasing doses of corticosteroids or local CNS-directed therapy to control their CNS disease. Patients on stable doses of corticosteroids for at least 7 days prior to receiving study drug may be included. 2. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome). 3. Clinically significant, uncontrolled heart disease (including history of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening) 4. Active viral hepatitis or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection. 5. Presence of any = CTCAE grade 2 treatment-related toxicity with the exception of alopecia, ototoxicity and peripheral neuropathy. 6. Systemic anticancer therapy within 21 days of the first study dose or 5 times its half-life, whichever is less. 7. Previous myeloablative therapy with autologous hematopoietic stem cell rescue within 8 weeks of the first study dose 8. Allogeneic stem cell transplant within 3 months prior to the first dose. Patients receiving any agent to treat or prevent graft-versus-host disease (GVHD) post bone marrow transplant are not eligible for this trial. 9. Radiotherapy (non-palliative) within 21 days prior to the first dose of drug (or within 6 weeks for therapeutic doses of MIBG or craniospinal irradiation). 10. Major surgery within 21 days of the first dose. Gastrostomy, ventriculo-peritoneal shunt, endoscopic ventriculostomy, tumor biopsy and insertion of central venous access devices are not considered major surgery, but for these procedures, a 48 hour interval must be maintained before the first dose of the investigational drug is administered. 11. Currently taking medications with a known risk of prolonging the QT interval or inducing Torsades de Pointes (Refer to Appendix 8). 12. Currently taking medications that are mainly metabolized by CYP3A4/5, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or the drug transporters Pgp (MDR1), BCRP, OATP1B1, OATP1B3, OCT1 and OCT2 and have a low therapeutic index that cannot be discontinued at least 7 days or 5 x reported elimination half-life prior to start of treatment with any of the investigational drugs and for the duration of the study (Refer to Appendix 9). 13. Known hypersensitivity to any study drug or component of the formulation. 14. Pregnant or nursing (lactating) females. 15. Vaccinated with live, attenuated vaccines within 4 weeks of the first dose of study drug.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I: To define or validate that the adult single agent RP2D of the selected drug or combination of drugs is safe in children/adolescents and/or that the PK profile is equivalent to that seen in adults, in pediatric/adolescent patients with malignancies which are recurrent or refractory to standard therapy. Phase II: To determine the preliminary activity (as measured by tumor response) of these agents in patients harboring specific molecular alterations or tumor types that may be associated with the mechanism of action of these drugs (i.e. molecularly enriched patient cohorts, where possible). ;Secondary Objective: Secondary: 1.To characterize the toxicity profile of the agent(s) in pediatric/ adolescent patients. 2.To characterize single or multiple-dose PK of the agent(s). 3.To evaluate the progression free survival and incidence of long responders (>6 months). 4.To evaluate whether the response rate is higher in the enriched population as compared to the non-enriched population overall, by targeted treatment and by arm. Exploratory: 1.To explore, define and/or validate pharmacodynamic biomarkers of target inhibition, where possible. 2.To explore relationships between measures of tumor expression of the molecular target(s), circulating tumor DNA and tumor growth. ;Primary end point(s): The recommended phase II dose (RP2D) will be defined as the adult recommended dose (adjusted for weight or BSA) if toxicity and PK profiling are similar in children and in adults, or a higher dose, providing it is below the maximum tolerated dose (MTD). The maximum tolerate dose (MTD) will be defined as the dose associated with or closest to 25% of DLTs in cycle 1. Dose Limiting Toxicities (DLT) will be defined using CTC-AE v4.03. ;Timepoint(s) of evaluation of this end point: Cycle 1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall response rate (ORR), duration of response (DOR), progression-free survival (PFS) Adverse Events PK parameters, including but not limited to plasma concentration time profiles, AUClast, AUCtau, Cmin, Cmax, Tmax, Clearance, Half-life time. Relationship between the molecular profile of the tumor samples and tumor growth measured as modification of the sum of the diameters of the target lesions over time. ;Timepoint(s) of evaluation of this end point: Overall response rate (ORR), duration of response (DOR) will be defined as the time period between the first documented response (PR or CR) and the time of progression. Duration of response for patients free of progression at the cut-off date will be censored at the last Imaging response scan date; progression-free survival (PFS) will be defined as the time from treatment initiation until the date of first documented progression or death from any cause. Patients alive and free of progression at the cut-off date will be censored at the last assessment date. | — |
Countries
Denmark, France, Italy, Netherlands, Spain, United Kingdom
Contacts
Public ContactCRA Manager
Gustave Roussy
Outcome results
None listed