E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced solid tumours including lymphoma and tumours of the central nervous system. |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065143 |
E.1.2 | Term | Malignant solid tumour |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 …. |
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E.2.2 | Secondary objectives of the trial |
• 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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 <10 years of age; Karnofsky score ≥70 for children ≥10 to <16 years; or ECOG Status 0-2 for patients age 16 and older. • Adequate organ functions. • Patient has a Body Surface Area (BSA) that allows evaluation of the current dose level. (For Ridaforolimus-containing Parts 2 and 3 only). • For females of reproductive potential, a negative pregnancy test must be documented within 72 hours of receiving the first dose of study medication. • A patient who is of reproductive potential agrees to use (or have their partner use). two adequate barrier methods of contraception to prevent pregnancy or to abstain from heterosexual activity throughout the study, starting with Visit 1 through 30 days after the last dose of study drug. Approved contraceptive methods include for example: intra uterine device, diaphragm with spermicide, cervical cap with spermicide, male condoms, or female condom with spermicide. Spermicides alone are not an acceptable method of contraception. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
• First 21 days of treatment for safety endpoint • First days 1-8 for PK endpoints |
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E.5.2 | 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. |
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E.5.2.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
France |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last Subject Last Visit (LSLV). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 26 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 26 |