Study On Pazopanib When Given With FOLFOX6 (Fluorouracil, Oxaliplatin, Leucovorin) Or CapeOx (Capecitabine, Oxaliplatin)

Study Overview
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Brief Summary
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This study will test the safety of treating colorectal cancer with a combination of drugs. The current standard treatments of FOLFOX6 or CapeOx will be give in combination with the GSK investigational drug pazopanib.

Official Title
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An Open-Label, Pharmacokinetic Study of the Safety and Tolerability of Pazopanib in Combination With FOLFOX 6 or CapeOx in Subjects With Colorectal Cancer

Conditions
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Neoplasms, Colorectal

Intervention / Treatment
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* Drug: Pazopanib
* Drug: FOLFOX 6
* Drug: CapeOx


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of locally advanced or metastatic colorectal cancer. No prior chemotherapy for metastatic disease. Presence of radiologically and/or clinically documented disease. Eastern Cooperative Oncology Group performance status of 0 or 1. Adequate bone marrow, hepatic, renal function, Urine Creatinine Ratio (UPC) of < A female subject must not be pregnant or breast feeding. Able to swallow and retain oral medications. Exclusion Criteria: Has had any major surgery, chemotherapy, hormone therapy, investigational agent, or radiotherapy within the last 28 days Prior treatment with pazopanib, or oxaliplatin. Known contraindications to the use of oxaliplatin, capecitabine, 5-fluorouracil, or folinic acid. Participation in any investigational study within 28 days prior to study treatment. Women who are pregnant or lactating. Poorly controlled hypertension. A history of cardiovascular disease, arrhythmias, or significant ECG abnormalities. Any history of stroke. Current use of therapeutic warfarin. Known brain metastases. History of disease significantly affecting gastrointestinal function or major resection of the stomach or small bowel. Active infections or other serious illness. History of allergy to platinum compounds or heparin. Poor venous access.

Ages Eligible for Study
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Minimum Age: 21 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FOLFOX 6 + Pazopanib<br>Subjects will receive escalating doses of Pazopanib in combination with FOLFOX 6. | Drug: Pazopanib<br>* Pazopanib is an oral inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-kit kinases<br>Drug: FOLFOX 6<br>* FOLFOX 6 treatment consists of intravenous (IV) oxaliplatin (100 milligram per meter^2[mg/m^2]), and folinic acid (400 mg/m^2), IV 5-fluorouracil bolus (400 mg/m^2) followed by IV 5-fluorouracil (2400 to 3000 mg/m^2) infusion over 48 hours on Day 1 of every 14-day cycle.<br>|
| Experimental: CapeOx + Pazopanib<br>Subjects will receive escalating doses of Pazopanib in combination with CapeOx. CapeOx treatment consisted of IV oxaliplatin (130 mg/m^2) on Day 1 plus oral capecitabine (1000 mg/m^2) twice daily on Days 2 through 14 of every 21-day cycle. Reduced CapeOx treatment was administered according to the same schedule as the CapeOx treatment, but the dose of capecitabine was reduced to 850 mg/m^2 twice daily. | Drug: Pazopanib<br>* Pazopanib is an oral inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-kit kinases<br>Drug: CapeOx<br>* CapeOx treatment consists of IV oxaliplatin (130 mg/m^2) on Day 1 plus oral capecitabine (1000 mg/m^2) twice daily on Days 2 through 14 of every 21-day cycle. Reduced CapeOx treatment will be administered according to the same schedule as the CapeOx treatment, but the dose of capecitabine will be reduced to 850 mg/m^2 twice daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma AUC(0-24) of pazopanib on Day 1, 14 and 21 Plasma AUC(0-46) of 5-FU and AUC(0-8) of platinum on Day 1 Plasma AUC(0-24) of capecitabine, 5-FU, and platinum on Day 1 |  | on Day 1, 14 and 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic endpoints (AUC, C24, Cmax, tmax, and half-life)collected predose and 1, 2, 3, 4, 5, 6, 8, and 24 hours on Day 1. Assessment of disease by imaging |  | collected predose and 1, 2, 3, 4, 5, 6, 8, and 24 hours on Day 1. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetics, colorectal cancer, pazopanib, capecitabine, CapeOx, 5-fluorouracil, oxaliplatin, combination therapy, FOLFOX 6