E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or refractory solid tumors or lymphoma in children Neuroblastoma Osteosarcoma Rhabdomyosarcoma Ewing sarcoma |
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E.1.1.1 | Medical condition in easily understood language |
Cancers that form in bone or soft tissue, the soft tissues in striated muscle, the large bones of the arm or leg or from immature nerve cells or solid cancers/lymphoma that come back in children |
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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 | PT |
E.1.2 | Classification code | 10025310 |
E.1.2 | Term | Lymphoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065147 |
E.1.2 | Term | Malignant solid tumor |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029260 |
E.1.2 | Term | Neuroblastoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10031291 |
E.1.2 | Term | Osteosarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039022 |
E.1.2 | Term | Rhabdomyosarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10015560 |
E.1.2 | Term | Ewing's sarcoma |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To establish the safety, maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of copanlisib in pediatric patients with a relapsed/refractory solid tumor or lymphoma |
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E.2.2 | Secondary objectives of the trial |
1. To characterize the PK of copanlisib 2. To assess the antitumor activity of copanlisib and to identify specific potential tumor type(s) for further development |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent form by patients and/or patients’ parents/legal guardians and age appropriate assent form by the patients obtained before any study specific procedure. 2. Male or female patients from 6 months to ≤ 21 years old at the time of study enrollment. 3. Confirmation of diagnosis: - Phase I: Patients must have histologic verification of a solid tumor or lymphoma malignancy at diagnosis for which there is no standard curative anti-cancer treatment or treatment is no longer effective and must have received ≥ 1 prior line of therapy. - Phase II: patients must have histologically verified tumor at initial diagnosis and radiologically or histologically confirmed status at inclusion as indicated in the following: neuroblastoma, osteosarcoma, rhabdomyosarcoma or Ewing sarcoma. - Patients with solid tumors must have measurable or evaluable (for neuroblastoma and Ewing sarcoma) disease. Tumor assessment will be done via computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography-computed tomography (PET-CT). Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, may be considered measurable if there has been demonstrated progression in the lesion. Bone scans (if clinically indicated) should be obtained within ≤ 4 weeks prior to the start of treatment. 4. Performance level: Lansky ≥ 50% for patients ≤ 16 years of age and Karnofsky ≥ 50% for patients > 16 years of age. 5. Adequate bone marrow, liver and renal function |
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E.4 | Principal exclusion criteria |
1. Active or uncontrolled infection (National Cancer Institute (NCI)-CTCAE Grade ≥ 2). 2. History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator). 3. Diabetes mellitus. 4. Uncontrolled arterial hypertension despite optimal medical management (per institutional guidelines). 5. Patients with central nervous system (CNS) malignancies. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Phase 1: The maximum tolerated dose (MTD) 2. Phase 1: Dose-limiting Toxicities(DLTs) 3. Phase 1: Number of subjects with Treatment-emergent Adverse Events(TEAEs) 4. Phase 1: Number of subjects with Serious Adverse Events (SAEs) 5. Phase 1: Number of subjects with Treatment-related Adverse Events (AEs). 6. Phase 2: Objective response rate (ORR) 7. Phase 2: Disease control rate (DCR) 8. Phase 2: Progression-free survival (PFS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Cycle 1 (28 days) 2. Cycle 1 (28 days) 3. Approximately 13 months 4. Approximately 13 months 5. Approximately 13 months 6. Up to 31 months 7. Up to 31 months 8. Up to 31 months |
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E.5.2 | Secondary end point(s) |
1. Phase 1: Copanlisib maximum drug concentration (Cmax) 2. Phase 1: Area under the curve (AUC(0-168)) 3. Phase 1: Objective response rate (ORR) 4. Phase 2: Duration of response (DOR) 5. Phase 2: PFS in each indication except for osteosarcoma 6. Phase 2: Overall survival (OS) 7. Phase 2: Number of subjects with Treatment-emergent AEs 8. Phase 2: Number of subjects with treatment emergent SAEs 9. Phase 2: Number of subjects with treatment-emergent clinically significant change in laboratory parameters, ECGs and vital signs |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Cycle 1 Day 1 and Day 15 2. Cycle 1 Day 1 and Day 15 3. Approximately 12 months 4. Up to 31 months 5. Up to 31 months 6. Up to 31 months 7. Up to 32 months 8. Up to 32 months 9. Up to 32 months |
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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 | Yes |
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 | No |
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 |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
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 | 5 |
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 | Yes |
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 | Yes |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |