Clinical trial NCT00777478: Capiri-sutent Phase-1 in Advanced Colo-rectal Cancer
Official title: A Phase I Dose Escalation Study With Sunitinib (SutentR) in Combination With Capecitabine and Irinotecan (Capiri) in Previously Treated Patients With Advanced Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Colorectal Cancer
Keywords: Sunitinib
Capecitabine
Irinotecan
colorectal cancer
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2008-10-22
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Maximum Tolerated Dose
timeFrame: after every completed doselevel
Secondary outcomes:
measure: determine the safety and toxicity profile using the CTCAE criteria.
timeFrame: after every completed doselevel
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: University Medical Center Nijmegen st Radboud
state: Gelderland
Study officials:
affiliation: UMCN st Radboud
name: C.M.L. van Herpen, MD, Phd
role: PRINCIPAL_INVESTIGATOR
References: