E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ovarian, Testicular, or Extragonadal germ cell tumours |
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E.1.1.1 | Medical condition in easily understood language |
Germ cell tumours develop from cells that produce eggs or sperm. However, it is also possible for a germ cell tumour to develop in other parts of the body. |
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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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10015800 |
E.1.2 | Term | Extragonadal primary germ cell tumour mixed stage I |
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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10015801 |
E.1.2 | Term | Extragonadal primary germ cell tumour mixed stage II |
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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10015802 |
E.1.2 | Term | Extragonadal primary germ cell tumour mixed stage III |
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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10043331 |
E.1.2 | Term | Testicular germ cell tumour mixed stage I |
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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10043332 |
E.1.2 | Term | Testicular germ cell tumour mixed stage II |
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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10043333 |
E.1.2 | Term | Testicular germ cell tumour mixed stage III |
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 | PT |
E.1.2 | Classification code | 10004433 |
E.1.2 | Term | Benign ovarian tumour |
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 | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006032 |
E.1.2 | Term | Borderline ovarian tumour |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1) To assess whether complete surgical resection followed by close observation and monitoring can maintain the excellent overall survival for patients when there is no visible disease left after surgery. 2) To compare two chemotherapy regimens of similar drugs (carboplatin vs. cisplatin) in the treatment of paediatric, adolescent and young adult patients with standard risk germ cell tumours i.e. to assess whether the drug with less anticipated severe side effects (carboplatin) is as effective as cisplatin in treating germ cell tumours.
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E.2.2 | Secondary objectives of the trial |
1) To compare the two chemotherapy regimens for the incidence of toxicity to the ears 2) To refine and validate a novel patient-reported measure of hearing (however, the UK is not taking part in this part of the trial) There are also a number of exploratory objectives: 1) To investigate correlation between tumour markers and clinical outcome 2) To compare the two chemotherapy regimens for self-reported nerve toxicity and other patient-reported outcomes 3) To assess how well a GCT responds to treatment, through measuring known tumour markers.
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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 |
‘Investigating circulating miRNAs’ sub-study Date: Version: 1.0 The aim of the sub-study is to investigate if a panel of four circulating microRNAs could be a universal specific and sensitive biomarker of diagnosis, recurrence and response to therapy to replace current surveillance imaging and potentially replace less sensitive and specific serum markers. Specific Objectives: • To investigate the prognostic significance of an established panel of four circulating miRNAs at diagnosis, during follow-up and at relapse in malignant GCTs. • To identify integrated messenger RNA/microRNA profiles in primary malignant GCTs that correlate with poor clinical outcomes. Samples for use on this sub-study will be collected in accordance with the trial Protocol under this ethical approval, however the analysis will be covered by a separate ethical approval. |
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E.3 | Principal inclusion criteria |
1. Histologic verification of a primary extracranial germ cell tumour (GCT) as outlined in any of the categories outline in the protocol. 2. Performance status corresponding to ECOG scores of 0, 1, 2 or 3. (Use Karnofsky for patients > 16 years of age and Lansky for patients ≤ 16 years of age). 3. For the low Risk Stratum patients must be < 50 years of age at enrolment. 4. For Standard Risk 1 patients must be < 11 years of age at enrolment. 5. For Standard Risk 2 patients must be ≥ 11 and < 25 years of age at enrolment. 6. For patients receiving chemotherapy (SR1 and SR2): a) Patients must have adequate renal function defined as; creatinine clearance or radioisotope GFR ≥70 mL/min/1.73 m2 or a serum creatinine based on age/gender as defined in the protocol. b) Patients must have adequate liver function defined as total bilirubin < or = 1.5 x upper limit of normal (ULN) for age, and – AST or ALT < 2.5 x upper limit of normal (ULN) for age (for the purpose of this study, the ULN for ALT is 45 U/L). c) Patients must have adequate pulmonary function defined as no evidence of dyspnoea at rest, no exercise intolerance, and a pulse oximetry > 94%. Pulmonary Function Tests are not required. |
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E.4 | Principal exclusion criteria |
1. Patients with any diagnoses not listed in the inclusion criteria of the protocol including: Pure dysgerminoma and pure seminoma, Pure mature teratoma, Pure immature teratoma COG Stage II - IV or FIGO Stage IC to IV, “Poor risk” GCT (age ≥ 11 years old and COG Stage IV ovarian, COG Stage III or IV EG, or IGCCC intermediate or poor risk testicular, or Primary CNS germ cell tumour). 2. Elevation of serum tumour markers without histologic confirmation. 3. Had no prior systemic therapy. 4. Had no prior radiation therapy except for CNS irradiation of brain metastases. 5. Patients with significant respiratory compromise due to either abdominal tumour limiting diaphragmatic excursion or pulmonary metastases. 6. Pregnancy and Breast Feeding - These criteria apply ONLY to patients who will receive chemotherapy (SR1 and SR2 patients): a) Female patients who are pregnant. b) Lactating females who plan to breastfeed their infants. c) Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.
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E.5 End points |
E.5.1 | Primary end point(s) |
1. LR: Stage I Ovarian Immature Teratoma, Grade 2 or 3: survival from the date of enrolment 2. LR: Stage I Malignant Germ Cell Tumour of Any Site: Survival from the date of enrolment 3. SR1: Event free survival (EFS) 4. SR2: EFS
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
For LR patients survival is defined as the time from the date of registration respectively to the date of the eventÍž patients will be censored at date last seen if lost to follow-up.
For SR patients EFS is defined as the time from the date of randomisation respectively to the date of the eventÍž patients will be censored at date last seen if lost to follow-up. |
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E.5.2 | Secondary end point(s) |
Feasibility outcome measure for delivery of carboplatin.
Ototoxicity: Patients will be monitored for hearing loss post-treatment. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Feasibility outcome measure for delivery of carboplatin: completion of protocol treatment with no more than one delay of more than 7 days in starting the next cycle – measured in the first 10 evaluable patients in SR1 and SR2.
Otoxicity: Occurrence of hearing loss at first off-treatment evaluation, 4 weeks after the last dose of platinum therapy. |
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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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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) | Yes |
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 | 19 |
E.8.5 | The trial involves multiple Member States | No |
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 |
India |
Japan |
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
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The end of the trial is defined as the completion of trial data collection. |
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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 | 10 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 10 |
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 | 1 |