Advanced solid tumours including lymphoma and tumours of the central nervous system. MedDRA version: 14.0 Level: LLT Classification code 10065143 Term: Malignant solid tumour System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or female age 6 to 17 years (included) on day of signing informed consent are eligible for Parts 1-3 of this study. Additionally, children ages 3 to 5 years are eligible for treatment in the dalotuzumab monotherapy dose escalation cohort (Part 1). • Histologic or cytologic diagnosis of a malignant solid tumour, including tumours of the central nervous system and lymphoma that have progressed despite standard therapy or for which no effective standard therapy is known. • Patients may have measurable (per RECIST 1.1) or non-measurable disease for Parts 1 and 2. Patients enrolled in Part 3 must have measureable disease. • Patient must be able to swallow tablets. (Patients to be enrolled into Parts 2 & 3). • Performance Status: Lansky Play Scale =70 for children =65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: • Patients currently receiving any other investigational agents or using any investigational devices. • Patients with leukaemia. • Patients who have previously received dalotuzumab or other IGF-1R inhibitors (Part 1). • History of allergic reactions attributed to compounds of similar chemical or biologic composition to dalotuzumab (Patients to be enrolled into Parts 1-3) or ridaforolimus (Patients to be enrolled into Parts 2-3). • Patient has persistent acute toxicity from previous therapy = Grade 2 by NCI CTCAE Version 4 (excluding alopecia, neuropathy, or hearing loss). • Uncontrolled intercurrent illness. • Pregnancy or females who are breastfeeding. • Patients to be enrolled into Parts 2-3 only: Patient has a requirement for concurrent treatment with medications that are inducers or inhibitors of cytochrome P450 (CYP3A). Patients should be off these medications for at least 2 weeks prior to the first dose of ridaforolimus. • Patient who has received an allogeneic stem cell transplant. The use of autologous stem cell rescue for high-dose chemotherapy is allowed any time prior to enrollment as long as patients meet baseline hematologic criteria. • Patient has poorly controlled Type 1 or 2 diabetes, defined as a fasting glucose >160 mg/dL.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1 • To define the dose limiting toxicities(DLT) and maximum tolerated dose(MTD) of dalotuzumab when administered as monotherapy to children from 3 to less than 18 years of age with advanced solid tumours. • To characterize the pharmacokinetics-PK (amount of study drug in the blood) of dalotuzumab when administered as monotherapy to children from 3 to less than 18 years of age with advanced solid tumours. Part 2-Combination Therapy: To be conducted if the Part 1 pharmacokinetics hypothesis is met in MK-8669 PN062 and the primary pharmacokinetics hypothesis is met in MK-8669 PN056. • To define the dose limiting toxicities ….;Secondary Objective: • To assess for anti-tumour activity of dalotuzumab and ridaforolimus. Anti-tumour activity will be assessed using RECIST criteria 1.1 • To compare change from baseline pAKT in platelet rich plasma blood between ridaforolimus monotherapy (historical data) and the ridaforolimus + dalotuzumab combination at the corresponding ridaforolimus dose levels. pAKT is a protein (biomarker) for the PI3K (phosphatidylinositol3 kinase) pathway that plays a role in multiple cellular processes. Biomarkers are used as an indicator of a biological state, they are measured in blood and the concentration reflects the severity or presence of a disease. Also an exploratory objective of the study will be to assess for anti-tumour activity of dalotuzumab and ridaforolimus and to examine pre-treatment gene expression profiles to identify potential predictive biomarkers of response to treatment with dalotuzumab monotherapy and ridaforolimus + dalotuzumab combination therapy.;Primary end point(s): • Safety endpoint: DLT rate • Pharmacokinetics: Mean Day-5 log AUC 0-24 for ridaforolimus. Mean Day-22 pre-dose serum concentration exceeds 25 ng/mL. for dalotuzumab.;Timepoint(s) of evaluation of this end point: • First 21 days of treatment for safety endpoint • First days 1-8 for PK endpoints | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Response rate defined as the proportion of patients whose best response is PR or CR (per RECIST 1.1). • Summary of change in pAKT between ridaforolimus monotherapy (historical data) and the ridaforolimus plus dalotuzumab combination.;Timepoint(s) of evaluation of this end point: • For the duration of study (until discontinuation) for efficacy • For the duration of study (until discontinuation) for pAKT | — |
Countries
Canada, France, United Kingdom, United States
Contacts
Public ContactGlobal Clinical Trials Operations
Merck Sharp & Dohme Corp., a subsidiary of Merck
Outcome results
None listed