Colorectal Cancer
Conditions
Keywords
Sunitinib, Capecitabine, Irinotecan, colorectal cancer
Brief 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.
Interventions
DRUGcapiri-sutent
A dose escalating study in a 3 + 3 design will be performed. At MTD dose 14 additional patients will be treated. First, the optimal dose of sunitinib in a continuous schedule will be determined, thereafter, further dose escalation of capecitabine and irinotecan will be investigated.
Sponsors
Radboud University Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Tolerated Dose | after every completed doselevel |
Secondary
| Measure | Time frame |
|---|---|
| determine the safety and toxicity profile using the CTCAE criteria. | after every completed doselevel |
Countries
Netherlands
Contacts
Primary ContactC.M.L. van Herpen, Md, Phd
Outcome results
None listed