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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I Dose Escalation Study With Sunitinib (SutentR) in Combination With Capecitabine and Irinotecan (Capiri) in Previously Treated Patients With Advanced Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: capiri-sutent


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: capiri-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.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose |  | after every completed doselevel | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| determine the safety and toxicity profile using the CTCAE criteria. |  | after every completed doselevel | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sunitinib, Capecitabine, Irinotecan, colorectal cancer