Capiri-sutent Phase-1 in Advanced Colo-rectal Cancer

• Status: Unknown status
• Trial end date: 2012-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of this Phase 1 study is to identify the recommended dose of capiri and of sunitinib for combination therapy subsequent phase II trials.

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

Details

• Lead Sponsor: Radboud University
• Treatments: Capecitabine; Irinotecan; Sunitinib

Criteria

Inclusion Criteria:

• Histological proof of colorectal cancer

• Patients should have failed one previous line of systemic treatment for advanced disease (and not more than one treatment line), either with fluoropyrimidine monotherapy or in combination with oxaliplatin and/or bevacizumab.

• No prior treatment with irinotecan or sunitinib

• Age ≥ 18 years

• WHO PS 0-1 (see Appendix 3, corresponding with Karnofsky ≥ 70% )

• Life expectancy ≥ 12 weeks

• Written informed consent

Exclusion Criteria:

• No measurable disease according to RECIST criteria.

• Prior anti-cancer therapy < 3 weeks before first dose. For cetuximab < 30 days or bevacizumab < 60 days prior to the first dose.

• Unresolved toxicity > CTC gr 1 from previous anti-cancer therapy (including radiotherapy) except for alopecia.

• Inadequate bone marrow function (Hb ≤ 5.6 mmol/L, absolute neutrophil count (ANC) ≤ 1.5 x 109/L, platelets ≤100 x 109/L)

• renal dysfunction (serum creatinine ≥ 1.5x ULN and glomerular filtration rate ≤ 50 ml/min)

• Prothrombin time (PT) and activated partial thromboplastin time (APTT) > 2x ULRR

• Hepatic dysfunction (serum bilirubin ≥ 1.5x ULN, serum transaminases ≥ 2.5 x ULN)

• Greater than +1 proteinuria on two consecutive dipsticks taken no less then 2 weeks apart unless urinary protein < 1,5 g in a 24 Hr period.

• Pregnant or lactating women

• History of clinical signs/symptoms of CNS metastases

• Previous intolerance of fluoropyrimidine therapy, known dihydropyrimidine dehydrogenase (DPD) deficiency. Known hypersensitivity to irinotecan or sunitinib of their excipients.

• No major surgery < 4 weeks prior to study entry.

• No radiotherapy < 4 weeks prior to study entry except for palliative radiotherapy at focal sites.

• Any evidence of concurrent severe or uncontrolled disease (i.e. uncontrolled hypertension, congestive heart failure, myocardial infarction < 6 months, chronic active infection, poorly regulated diabetes mellitus)

• Any previous significant cardiovascular event during previous fluoropyrimidine therapy (i.e.

myocardial ischemia or infarction, arterial thrombosis, pulmonary emboli)

• Mean Qtc with Bazetts correction > 470 msec in screening ECG, or a history with familial long QT syndrome

• Significant haemorrhage (>30 ml bleeding/episode in the last 3 months) or haemoptysis (>5 ml fresh blood in previous 4 weeks)

• History of impairment of gastrointestinal function or -disease that may significantly impair the absorption of oral drugs (i.e. uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome, bowel obstruction, or inability to swallow tablets)

• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

• Concomitant use medication that may significantly affect hepatic cytochrome P450 drug metabolizing activity by way of enzyme induction or inhibition < 2 weeks if the first dose and throughout the study period (see Appendix 2)

• Other concomitant anti-cancer therapy.