E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent Malignancies (recurrent solid tumors): Target tumor types were osteosarcoma, Ewing sarcoma/peripheral
PNET, rhabdomyosarcoma, neuroblastoma (measurable disease), neuroblastoma (metaiodobenzylguanidine
[MIBG]+ evaluable disease), ependymoma, medulloblastoma/supratentorial PNET, and non-brainstem
high-grade glioma. |
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E.1.1.1 | Medical condition in easily understood language |
Recurrent Malignancies (recurrent solid tumors) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
The primary objective of Study H3E-MC-JMHW (JMHW) was to estimate the response
rates to pemetrexed administered intravenously every 21 days in children with relapsed or
refractory osteosarcoma, Ewing sarcoma/peripheral PNET, rhabdomyosarcoma,
neuroblastoma, ependymoma, medulloblastoma/supratentorial PNET, or non-brainstem
high-grade glioma and to further define and describe the toxicities of pemetrexed. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study were:
• to examine the relationship between the presence of the C677T polymorphism of
the methylene tetrahydrofolate reductase gene and toxicity of patients being
treated with pemetrexed
• to examine the relationship between the presence of a polymorphism in the TS
gene and/or gene promoter and toxicity of patients being treated with pemetrexed
• to examine the relationship between response and tumor expression of the
enzymes TS, DHFR, GARFT, reduced folate carrier, folylpolyglutamate synthase,
and gamma-glutamyl hydrolase. Also, the relationship between response and
methylthioadenosine phosphorylase deletion status will be examined.
The pharmacogenetic and correlative studies were optional and required a separate
consent. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must have osteosarcoma, Ewing's sarcoma, medulloblastoma, neuroblastoma, rhabdomyosarcoma, ependymoma or high-grade non-brainstem glioma
•Measurable disease
•Eastern Cooperative Oncology Group (ECOG) performance 0,1,2
•Adequate renal, liver and bone marrow function
•Patient's current disease state must be one with no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
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E.4 | Principal exclusion criteria |
Growth factors that support platelet or white cell number or function must not have been administered within the last 7 days prior to enrollment (14 days if Neulasta)
•Patients with central nervous system (CNS) tumors who have not been on a stable or decreasing dose of dexamethasone or other corticosteroid for 7 days prior to enrollment
•Patients with uncontrolled infection
•Patients who have received pemetrexed previously
•Patients with pleural effusions or ascites
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of Participants With Overall Tumor Response (Response Rate) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time Frame: baseline to measured progressive disease (up to 1 year) |
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E.5.2 | Secondary end point(s) |
Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug [ Time Frame: every cycle (up to 2 years and 7 months) ]
Pharmacogenomics - Measure the Response of Genes Related to Toxicity [ Time Frame: baseline ]
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Number of Patients With Adverse Events, Discontinuations, or Deaths Possibly Due to Study Drug [ Time Frame: every cycle (up to 2 years and 7 months) ]
Pharmacogenomics - Measure the Response of Genes Related to Toxicity [ Time Frame: baseline ]
|
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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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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) | 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 | 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 | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
|
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
|
Last visit of the last subject undergoing the trial |
|
E.8.9 Initial estimate of the duration of the trial |
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 | 5 |