capiri-sutent phase-1 in advanced colo-rectal cancer

Conditions: Colorectal Cancer

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.


Eligibility 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.

Keywords: sunitinib capecitabine irinotecan colorectal cancer