E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Desmoplastic small round cell tumour (DSRCT) |
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E.1.1.1 | Medical condition in easily understood language |
Desmoplastic small round cell tumour |
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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 | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064581 |
E.1.2 | Term | Desmoplastic small round cell 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 |
To evaluate the efficacy of ramucirumab in combination with cyclophosphamide and vinorelbine compared with cyclophosphamide and vinorelbine in pediatric and young adult patients with DSRCT (DSRCT= desmoplastic small round cell tumor). |
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E.2.2 | Secondary objectives of the trial |
-To evaluate the safety and tolerability of ramucirumab in combination with cyclophosphamide and vinorelbine compared with cyclophosphamide and vinorelbine in pediatric and young adult patients with DSRCT
- To characterize the PK of ramucirumab when co-administered with cyclophosphamide and vinorelbine in pediatric and young adult patients with DSRCT
- To assess the immunogenicity of ramucirumab when co-administered with cyclophosphamide and vinorelbine in pediatric and young adult patients with DSRCT |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients with relapsed, recurrent, or refractory DSRCT.
- Patients must be 12 months to ≤29 years of age at the time of study enrollment.
- Patients must have received at least one prior line of systemic treatment, have measurable disease by RECIST 1.1, and must not be eligible for surgical resection at time of enrollment.
- Patients who have a Lansky (<16 years of age; Lansky et al. 1987) or Karnofsky (≥16 years of age; Karnofsky et al. 1948) performance score of at least 50.
- Patient with adequate hematologic, coagulation, liver, cardiac, renal and bladder function, and adequate blood pressure (BP) control as per protocol. |
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E.4 | Principal exclusion criteria |
- Patients who have had allogeneic bone marrow or solid organ transplant are excluded.
- Patients who have active infections requiring therapy.
- Patients who have a history of fistula, gastrointestinal (GI) ulcer or perforation, or intra-abdominal abscess within 3 months of study enrolment are not eligible.
- Patients with a bowel obstruction, extensive intestinal resection or history or presence of inflammatory enteropathy or other GI pathology as per protocol.
- Patients with a history of hepatorenal syndrome.
- Patients with evidence of active bleeding or a history of significant (≥Grade 3) bleeding event, deep vein thrombosis requiring medical intervention (including pulmonary embolism), hemoptysis or other signs of pulmonary haemorrhage, or esophageal varices within 3 months of enrollment are not eligible.
- Patients with a bleeding diathesis or vasculitis are not eligible.
- Patients with a history of central nervous system (CNS) arterial/venous thromboembolic events (VTEs) including transient ischemic attack (TIA) or cerebrovascular accident (CVA) within 6 months of study enrollment are not eligible.
- Patients with myocardial infarction or unstable angina within the prior 6 months.
- Patients with significant vascular disease or peripheral vascular disease.
- Patients with a history of hypertensive crisis or hypertensive encephalopathy within 6 months of study enrollment are not eligible.
- Patients who have non-healing wound, unhealed or incompletely healed fracture, or a compound (open) bone fracture at the time of enrolment are not eligible.
- Patients previously treated and progressed on combination cyclophosphamide and vinorelbine regimen. (Patients who received combination as maintenance therapy, without progression, would be eligible.)
- Patients with known hypersensitivity to cyclophosphamide or vinorelbine.
- Patients who have previously received any exposure to ramucirumab are not eligible.
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E.5 End points |
E.5.1 | Primary end point(s) |
progression-free survival (PFS) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary analysis will be triggered when PFS events have occurred for approximately 80% of the enrolled patients |
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E.5.2 | Secondary end point(s) |
Serious adverse event, Adverse event, Safety laboratory assessments, Vital signs, Overall response rate, Duration of response, Complete response, Incidence of immunogenicity, Cmax (maximum concentration) and Cmin (minimum concentration) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | 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 | Yes |
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.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
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 |
Australia |
Belgium |
France |
Germany |
Italy |
Japan |
Netherlands |
Spain |
United Kingdom |
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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LVLS - Last visit or last scheduled procedure for the last patient. |
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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 | 7 |
E.8.9.1 | In the Member State concerned days | 19 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 19 |