E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rhabdomyosarcoma, non-rhabdomyosarcomatous soft tissue sarcoma (including synovial sarcoma, alveolar soft part sarcoma and desmoplastic small round cell tumor), Ewing sarcoma/peripheral Primitive Neuro Ectodermal Tumor (PNET), hepatoblastoma, neuroblastoma (measurable and evaluable), and osteosarcoma |
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E.1.1.1 | Medical condition in easily understood language |
Children, adolescents and young adults have one of the above tumors that have come back after treatment or is not responding to current treatment. |
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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 | HLT |
E.1.2 | Classification code | 10019825 |
E.1.2 | Term | Hepatoblastomas |
E.1.2 | System Organ Class | 100000005101 |
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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 | 15.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10041299 |
E.1.2 | Term | Soft tissue sarcomas |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
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 | HLT |
E.1.2 | Classification code | 10039023 |
E.1.2 | Term | Rhabdomyosarcomas |
E.1.2 | System Organ Class | 100000143528 |
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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 determine the investigator- assessed objective response rate of pazopanib in children, adolescents and young adults (patients) with relapsed or refractory solid tumors of the following types (each defining a cohort):
1. rhabdomyosarcoma,
2. non-rhabdomyosarcomatous soft tissue sarcoma, or
3. Ewing sarcoma/peripheral Primitive Neuro Ectodermal Tumor (PNET).
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E.2.2 | Secondary objectives of the trial |
To determine the investigator- assessed objective response rate of pazopanib in children, adolescents, and young adults (patients)
1 osteosarcoma,
2 neuroblastoma (measurable),
3 neuroblastoma (evaluable), or
4 hepatoblastoma
•To further define and describe the toxicities of oral pazopanib
•To further characterize the pharmacokinetics (PK) of pazopanib after administration of the powder suspension formulation
•To determine progression free-survival
•To determine the time to progression
•To determine the therapeutic activity
•To assess duration of response
•To further examine the biologic relationship between tumor response and angiogenic cytokines.
•To assess the genotype/phenotype relationships of VEGF in children with soft tissue sarcoma.
•To further explore pazopanib pharmacokinetic/pharmacodynamic
•To assess overall survival (OS) in patients with relapsed or refractory solid tumors per cohort |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Age: Patients must be at least 1 year and less than or equal to 18 years of age at the time of study entry.
•Diagnosis: Patients must have had histologic verification of one of the malignancies listed below at original diagnosis or at relapse.
1.Rhabdomyosarcoma
2.Non-rhabdomyosarcomatous Soft Tissue Sarcoma (including desmoplastic small round cell tumor)
3.Ewing Sarcoma/Peripheral PNET
4.Osteosarcoma
5.Neuroblastoma (Measurable)
6.Neuroblastoma (Evaluable)
7.Hepatoblastoma
•Patient must have disease that has either relapsed or is refractory to prior therapy
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E.4 | Principal exclusion criteria |
•Pregnant or breast-feeding women are not eligible for this study
•Concomitant Medications
1.Corticosteroids: Patients requiring corticosteroid who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible.
2.Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible.
3.Anti-Cancer Agents or Radiation Therapy: Patients who are currently receiving other anti-cancer agents or radiation therapy are not eligible.
4.Anti-hypertensive: Patients who are currently receiving more than one anti-hypertensive medication (Grade 3) or whose blood pressure is not controlled (i.e. as defined in Section 3.2.8.) are not eligible for study enrollment.
5.Anti-coagulation: Patients must not be on therapeutic anticoagulation. ((Warfarin (coumadin®) and/or low molecular weight heparin are prohibited.) Prophylactic anticoagulation (ie intraluminal heparin) of venous or arterial access devices is allowed.
6.CYP3A4 Substrates and drugs causing QTc prolongation: Patients receiving drugs with a known risk of torsades de pointes are not eligible. See Appendices IIIA and IIIB and Section 4.8 for a list of enzyme inducing, enzyme inhibiting and other adversely interacting drugs and the appropriate washout periods required prior to study enrollment
Note: This list includes the prohibition of grapefruit juice for 14 days prior to enrollment and while receiving pazopanib.
7.Thyroid Replacement Therapy: Patients who require thyroid replacement therapy are not eligible if they have not been receiving a stable replacement dose for at least 4 weeks prior to study enrollment
•Patients who are unable to swallow tablets or liquid are not eligible. Pazopanib cannot be administered via NG tube or G-tube |
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective response rate (ORR) for the 3 tumor types of primary interest |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary analysis will be performed 20 weeks after LPFV in the 3 cohorts of primary interest |
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E.5.2 | Secondary end point(s) |
ORR for the 4 tumor types of secondary interest
Progression-free survival (PFS)
Overall survival (OS)
Time to progression (TTP)
Safety measures
Duration of response (DoR) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
rimary analysis will be performed 20 weeks after LPFV in the 3 cohorts of primary interest |
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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 | Yes |
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) | No |
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) | 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 | 7 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
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 |
Czech Republic |
France |
Hungary |
Italy |
Slovakia |
Spain |
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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One year from the date of the last patient’s first visit. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |