E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with multiple brain metastases (>1) of solid tumors, who have not received prior external beam irradiation to the brain |
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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 |
To evaluate the safety of the administration of radioimmunotherapy with 131I-L19SIP combined with whole brain radiation treatment (the standard treatment)and to determine the selective uptake of the study drug (131I-L19SIP) in the brain lesions. |
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E.2.2 | Secondary objectives of the trial |
To determine the anti-tumour activity of 131I-L19SIP at the level of the brain metastases as well as on overall tumor growth. Furthermore the duration of response and the quality of life are evaluated. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Unresectable multiple brain metastasis (>1) from histologically or cytologically confirmed solid tumors. In exceptional cases also patients with a single brain metastasis if not amenable for surgical treatment might be included. •Males or females, age > 18 years •Measurable disease defined as at least one metastatic brain lesion that can be accurately and serially measured by the modified RECIST criteria (version 1.1) •Prior therapy for metastatic disease allowed •GPA score 2&3 [50] •Life expectancy of at least 12 weeks •Absolute neutrophil count > 1.5 x 109/L, hemoglobin > 9.0 g/dL and platelets > 100 x 109/L •Total bilirubin ≤ 30 µmol/L (or ≤ 2.0 mg/Dl) •ALT and AST ≤ 2.5 x the upper limit of normal (5.0 x ULN for patients with hepatic involvement with tumor •Serum creatinine < 1.5 x ULN •All toxic effects of prior therapy must have resolved to ≤ Grade 1 unless otherwise specified above •Negative serum pregnancy test (for women of child-bearing potential only) at screening •Patients with microhaemorrhage can be included if the microhaemorrhage does not appear to significantly contribute to symptoms caused by the particular brain lesion and if the microhaemorrhage does not appear to significantly contribute to a possible mass effect of the brain lesion in question.
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E.4 | Principal exclusion criteria |
•Primary ocular melanoma •Patients with brain metastasis amenable for surgical excision or stereotactic irradiation (radiosurgery) •Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (TA, Tis & Ti) or any cancer curatively treated < 5 years prior to study entry •Patients with history of whole brain irradiation •History of HIV infection or infectious hepatitis B or C •Presence of active infections (e.g. requiring antimicrobial therapy) or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study. •Inadequately controlled cardiac arrhythmias including atrial fibrillation •Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria) •Uncontrolled hypertension •Ischemic peripheral vascular disease (Grade IIb-IV) •Severe diabetic retinopathy •Active autoimmune disease •History of organ allograft or stem cell transplantation •Recovery from major trauma including surgery within 4 weeks prior to administration of study treatment •Breast feeding female •Previous in vivo exposure to monoclonal antibodies for biological therapy in the 6 weeks before administration of study treatment •Growth factors or immunomodulatory agents within 7 days of the administration of study treatment •Patients in need of systemic treatment for rapidly progressive systemic disease during study treatment and up to 6 weeks after injection of therapeutic 131I-L19SIP •Hyperthyroidism or autonomous thyroid nodule
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure for this study is the determination of radiation dosimetry for healthy organs and for each target lesion either using SPECT methodologies [1], planar images [2] or ImmunoPET [3]. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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 | 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 | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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Last visit of the last subject undergoing the trial |
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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 | 1 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |