E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced solid tumors including lymphoma and tumors 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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065252 |
E.1.2 | Term | Solid tumor |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10007960 |
E.1.2 | Term | Central nervous system neoplasms malignant NEC |
E.1.2 | System Organ Class | 100000004852 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- To define the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of ridaforolimus when administered to children from 6 to less than 18 years of age with advanced solid tumors. - Characterize the pharmacokinetics (PK) of ridaforolimus when administered to children from 6 to less than 18 years of age with advanced solid tumors.
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E.2.2 | Secondary objectives of the trial |
- Assess for anti-tumor activity of ridaforolimus. For patients with measurable disease, overall response will be assessed every two cycles according to RECIST 1.1. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Merck will conduct Future Biomedical Research on specimens routinely and specifically collected during this clinical trial. This research may include genetic analyses (DNA), and/or the measurement of other analytes. |
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E.3 | Principal inclusion criteria |
1. The parent/guardian and patient voluntarily agree to participate by providing written informed consent and assent. The parent/guardian and patient may also provide consent and assent for Future Biomedical Research. However, they may participate in the main trial without participating in Future Biomedical Research. 2. Male or female age 6 to 17 years (included) on day of signing informed consent. 3. Histologic or cytologic diagnosis of a malignant solid tumor, including tumors of the central nervous system and lymphoma that have progressed despite standard therapy or for which no effective standard therapy is known. Patients who have received standard therapy and continue to have biopsy proven residual stable disease are eligible. In the absence of a biopsy, patients with sarcoma would be eligible on the basis of persistent PET activity or by MIBG in neuroblastoma. 4. Patients may have measurable (per RECIST 1.1) or non-measurable disease. 5. Patients with brainstem glioma or intrinsic pontine glioma do not require biopsy proof of the diagnosis. 6. For patients with CNS tumors ONLY: if baseline neurotoxicity is due to primary tumor involvement r post-operative complications, Grade 3 neurotoxicity is allowed if stable. 7. Patient must be able to swallow tablets. 8. 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. 9. Adequate organ functions as indicated by laboratory values: 10. Patient has a Body Surface Area (BSA) that allows evaluation of the current dose level. 11. For females of reproductive potential, a negative pregnancy test must be documented within 72 hours of receiving the first dose of study medication. 12. 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 |
1. Patients currently receiving any other investigational agents or using anyinvestigational devices. 2. Patients with leukemia. 3. Patients who have previously received ridaforolimus, rapamycin, or other rapamycin analogs. 4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to ridaforolimus. 5. Patient has persistent acute toxicity from previous therapy ≥Grade 2 by NCI CTCAE Version 4 (excluding alopecia, neuropathy, or hearing loss). 6. Uncontrolled intercurrent illness despite adequate therapy. 7. Pregnancy or females who are breastfeeding. 8. Known HIV, HBV, or HCV positive. Testing for HIV, HBV, or HCV is not required. 9. Patient who has received an allogeneic stem cell transplant. The use of autologous stem cell rescue after high-dose chemotherapy is allowed any time prior to enrollment as long as patients meet baseline hematologic criteria. 10. 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. 11. 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) |
1. Number of Participants Experiencing a Dose Limiting Toxicity (DLT) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4.0) 2. Area Under the Concentration-Time Curve of Ridaforolimus From Time 0 to 24 Hours (AUC0-24 hr) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Time Frame: Cycle 1 (cycle = 28 days) 2. Time Frame: Day 5 of Cycle 1 [28-day cycle]: pre-dose (0.0 hours) and 0.5, 1.0, 2.0, 4.0, 8.0, and 24.0 hours after administration of ridaforolimus |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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 | Yes |
E.7.1.3.1 | Other trial type description |
Pediatric pharmacokinetic |
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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 | Yes |
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.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 25 |