Capiri-sutent Phase-1 in Advanced Colo-rectal Cancer (sutent-capiri)

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Colorectal Cancer	Drug: capiri-sutent	Phase 1

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	32 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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 Start Date :	December 2008
Estimated Primary Completion Date :	May 2012
Estimated Study Completion Date :	December 2012

Arms and Interventions

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Intervention Details:

• 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.

Outcome Measures

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Primary Outcome Measures :

1. Maximum Tolerated Dose [ Time Frame: after every completed doselevel ]

Secondary Outcome Measures :

1. determine the safety and toxicity profile using the CTCAE criteria. [ Time Frame: after every completed doselevel ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

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Contacts

Contact: C.M.L. van Herpen, Md, Phd	0031 24 3610353	c.vanherpen@onco.umcn.nl

Locations

Netherlands
University Medical Center Nijmegen st Radboud	Recruiting
Nijmegen, Gelderland, Netherlands, 6525 GH
Principal Investigator: C.M.L van Herpen, Md, Phd

Sponsors and Collaborators

Radboud University

Investigators

Principal Investigator:	C.M.L. van Herpen, MD, Phd	UMCN st Radboud

More Information

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Responsible Party:	Radboud University
ClinicalTrials.gov Identifier:	NCT00777478 History of Changes
Other Study ID Numbers:	UMCNONCO20083
First Posted:	October 22, 2008
Last Update Posted:	February 3, 2012
Last Verified:	January 2012

Keywords provided by Radboud University:

Sunitinib; Capecitabine; Irinotecan; colorectal cancer

Additional relevant MeSH terms:

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Capecitabine; Irinotecan; Sunitinib	Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors