E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pediatric solid tumors for which prior treatment has proven to be ineffective (i.e., relapsed or refractory) or intolerable |
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E.1.1.1 | Medical condition in easily understood language |
Pediatric solid tumors for which prior treatment has proven to be ineffective (i.e., relapsed or refractory) or intolerable |
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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 | 19.0 |
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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029547 |
E.1.2 | Term | Non-Hodgkin's 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 | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047987 |
E.1.2 | Term | Wilms' tumor |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020328 |
E.1.2 | Term | Hodgkin's 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 | 19.0 |
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) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
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) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10075333 |
E.1.2 | Term | Soft tissue sarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
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 evaluate the safety and tolerability of atezolizumab (MPDL3280A), focusing on the nature, frequency, and severity of serious and non-serious adverse events, as well as effects on laboratory values, vital signs, or other safety biomarkers |
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E.2.2 | Secondary objectives of the trial |
To characterize the pharmacokinetics of atezolizumab (MPDL3280A); To evaluate the immune response to atezolizumab (MPDL3280A) based on the incidence of anti-therapeutic antibodies (ATAs); to evaluate the anti-cancer activity of atezolizumab (MPDL3280A) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Age at study entry < 30 years
•Weight ≥ 3kg
•Histologically or cytologically confirmed solid tumor,with
known or expected PD-L1 pathway involvement for which prior treatment had proven to be ineffective (i.e., relapsed or refractory) or intolerable
•Current disease state for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
•Disease that is measurable or evaluable
•Archival tumor tissue block available for submission, or willingness to undergo a core or excisional biopsy prior to enrollment
•Lansky Performance Status (patients <16 years old) or Karnofsky
Performance Status (patients > 16 years old) > 50
•Life expectancy >3 months
•For patients of childbearing potential: agreement to remain abstinent
(refrain from heterosexual intercourse) or use two adequate methods of
contraception, including at least one method with a failure rate of < 1%
per year, during the treatment period and for at least 5 months after the
last dose of study drug |
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E.4 | Principal exclusion criteria |
•Primary central nervous system (CNS) malignancy, untreated CNS metastases or treated but symptomatic CNS metastases
•Prior allogeneic hematopoietic stem-cell transplant or prior solid-organ transplantation
•Pregnant or lactating, or intending to become pregnant during the study
•Treatment with a live vaccine or a live, attenuated vaccine within 4
weeks prior to initiation of study drug Prior treatment with CD137
agonists or immune checkpoint blockade therapies, including anti-
CTLA4, anti-PD-1, or anti-PD-L1 therapeutic antibodies
•Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to initiation of study drug, or anticipated requirement for systemic immunosuppressive medications during the trial
•Current treatment with therapeutic anticoagulants
•Known active infection (excluding fungal infection of nail beds) within 28 days prior to initiation of study drug that has not completely resolved
•History of autoimmune disease
•History of severe asthma or presence of uncontrolled asthma at the time of screening evaluation |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety and tolerability: All adverse events, all serious adverse events
Pharmacokinetic: PK parameters are to include Cmax (Day 1 Cycle 1) and Cmin. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
PK collections are to include at least 2 samples on Day 1 of Cycle 1 (prior to infusion and one 30 minutes after the infusion). Pre -dose trough samples will be taken on Day 1 of cycles Cycles 2, 3, and 8, 12 and 16 (and every 8 cycles thereafter). In addition, a sample will be taken at the end of treatment and at least 90 days after last dose of study drug (washout) |
|
E.5.2 | Secondary end point(s) |
Immunogenicity: Anti therapeutic antibodies
Efficacy: objective response rate and progression-free survival
Exploratory endpoints for efficacy: Duration of objective response and overall survival
Other exploratory endpoints: Determination of pharmacodynamic parameters of atezolizumab (MPDL3280A), including PD-L1 status evaluation (archival tumor tissue; blood for PD evaluations will be drawn pretreatment and on day 1 of cycles 2, 3, 8, 12, 16 and every subsequent 8th cycle. In addition, blood for PD will be drawn at the time of study drug discontinuation and at least 90 days after the last dose of study drug (washout). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Anti therapeutic antibodies - pretreatment, and on Day 1 of Cycles 2,3, and 8 12, 16 and every 8 cycles thereafter. A sample will also be drawn at the end of treatment and after washout.
ORR and PFS -tumor assessment will be performed every two cycles [6 weeks] for the first 8 cycles; following cycle 8 tumor assessments will be done every 4 cycles.
Duration of OR and OSS -tumor assessment will be performed every two cycles [6 weeks] for the first 8 cycles; following cycle 8 tumor assessments will be done every 4 cycles.
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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 | No |
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 |
first in paediatric population |
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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.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 44 |
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 |
Austria |
Canada |
Denmark |
France |
Germany |
Ireland |
Israel |
Italy |
Netherlands |
Spain |
Switzerland |
United Kingdom |
United States |
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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
|
The end of this study is defined as the date when LPLV occurs, or 5 years after the last patient
is enrolled, whichever occurs first. |
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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 | 7 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 1 |