131I-L19SIP Radioimmunotherapy (RIT) in Combination With External Beam Radiation in Patients With Multiple Brain Metastases From Solid Tumors

Inclusion Criteria: * 6.3.1 Inclusion Criteria for Dosimetric Study Part (diagnostic 131I-L19SIP or 124I-L19SIP) and therapeutic study part * Unresectable multiple brain metastasis 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 * RPA Class II * Life expectancy of at least 12 weeks * 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 * If of childbearing potential, agreement to use highly effective contraceptive methods (e.g., established use of oral, injected or implanted hormonal methods, placement of intrauterine device or intrauterine system, use of condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, male sterilization or true abstinence) beginning at the screening visit and continuing until 3 months following last treatment with study drug. * In case of treated males (including men who have had vasectomies) who have a partner who is pregnant or of child-bearing potential, agreement to use condoms beginning at the screening visit and continuing until 3 months following last treatment with study drug. * 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. Additional Inclusion Criteria for Therapeutic Study Part * Absolute neutrophil count \> 1.0 x 109/L, hemoglobin \> 8.0 g/dL (packed red cell transfusions allowed), and platelets \> 100 x 109/L * Total bilirubin ≤ 30 µmol/L (or ≤ 2.0 mg/dL). For patients with liver involvement with tumor total bilirubin ≤ 45 µmol/L (or ≤ 3.0 mg/dL). * ALT and AST ≤ 2.5 x the upper limit of normal (10 x ULN for patients with hepatic involvement with tumor 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 * Pregnant woman * 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 associated with a moderate or significant potential of hematotoxicity for rapidly progressive systemic disease during study treatment and up to 4 weeks after injection of therapeutic 131I-L19SIP. * Hyperthyroidism or autonomous thyroid nodule