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

• Status: Completed
• Trial end date: 2018-10-30
• Target enrollment: 0
• Participant gender: All

Summary

This study evaluates the safety, tolerability and pharmacokinetics of oral administration of irinotecan in adult patients. Oral irinotecan will be administered as monotherapy in a dose escalation trial to establish the Maximal Tolerated Dose. Totally 25 patients will be treated with irinotecan tablets as mono-therapy. As an extension trial 12 patients will be treated with oral irinotecan in combination with oral capecitabine

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Dorte Nielsen
• Treatments: Camptothecin; Capecitabine; Irinotecan

Criteria

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.