Safety, Tolerability and Pharmacokinetics of Oral Tablet of Irinotecan in Adult Patients With Solid Tumors

Inclusion Criteria:

• Signed written Informed Consent
• 18 years of age or older
• Capable of understanding the protocol requirements and risk associated with the study
• Patients must have histological confirmed malignancy (solid tumor) that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
• Patients with either measurable disease according to RECIST 1.1 or non-measurable disease
• Performance status 0-1 (ECOG)
• Life expectancy ≥ 3 months
• Coagulation INR < 1.3 and APTT within normal limits
• WBC ≥ 3000/mm3
• Absolute neutrophil count ≥ 1500/mm3
• Hemoglobin ≥ 6.0 mmol/L
• Platelet count ≥ 100.000/mm3
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN AST and ALT ≤ 2.5 times ULN. For patients with liver metastasis adequate hepatic function is defined by aspartate aminotransferase (AST) ≤ 5 x ULN and alanine aminotransferase ALT ≤ 5 x ULN
• No severe or uncontrolled renal condition (creatinine ≤ than 1.5 ULN)
• No significant cardiovascular disease (New York Heart Association Class III and IV)
• No other severe cardiac condition not defined above
• No significant cardiovascular disease (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year prior for patients to be enrolled and treated in combination with oral capecitabine
• No severe or uncontrolled pulmonary condition
• No known prior hypersensitivity reaction to irinotecan
• No known prior hypersensitivity to capecitabine or 5-fluorouracil for patients to be enrolled and treated in combination with oral capecitabine
• No chronic enteropathy (e.g. active inflammatory bowel disease, extensive intestinal resection or chronic diarrhea)
• No bowel obstruction or sub-obstruction
• No prior history of intestinal malabsorption
• Patients have to be able to swallow normally and have to be willing to comply with the intake of tablets
• No psychiatric condition that would preclude study participation
• No co-existing active infection requiring antibiotics or any co-existing medical conditions likely to interfere with study procedures
• No other condition that will preclude study participation
• A negative pregnancy test for women of childbearing potential. For men and women of child-producing potential, the use of effective contraceptives methods during the study and at least 3 months after discontinuations of the study drug is required.
• Not pregnant or nursing
• Peripheral neuropathy NCI CTCAE grade less than 2 for patients to be enrolled and treated in combination with oral capecitabine
• The patient is willing and able to comply with hospitalization for treatment and scheduled follow-up visits and examinations

Exclusion Criteria:

• Simultaneous participation in any other study involving investigational drugs or having participated in a study within 4 weeks prior to start of study treatment
• Symptomatic brain metastases
• Intake of any prohibited concomitant medication
• Known Dihydropyrimidine dehydrogenase (DPD) deficiency for patients to be enrolled and treated in combination with oral capecitabine.