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

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT00387387

Collaborator

(none)

Enrollment

Locations

Arms

33.8

Actual Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Neoplasms, Colorectal	Drug: Pazopanib Drug: FOLFOX 6 Drug: CapeOx	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

50 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 20, 2006

Actual Primary Completion Date :

Aug 14, 2009

Actual Study Completion Date :

Aug 14, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FOLFOX 6 + Pazopanib Subjects will receive escalating doses of Pazopanib in combination with FOLFOX 6.	Drug: Pazopanib Pazopanib is an oral inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-kit kinases Drug: FOLFOX 6 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.
Experimental: CapeOx + Pazopanib 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 Pazopanib is an oral inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-kit kinases Drug: CapeOx 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.

Arm

Intervention/Treatment

Experimental: FOLFOX 6 + Pazopanib

Subjects will receive escalating doses of Pazopanib in combination with FOLFOX 6.

Drug: Pazopanib

Pazopanib is an oral inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-kit kinases

Drug: FOLFOX 6

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.

Experimental: CapeOx + Pazopanib

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

Pazopanib is an oral inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-kit kinases

Drug: CapeOx

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.

Outcome Measures

Primary Outcome Measures

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

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.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Hyderabad, Andhra Pradesh		India	500482
2	GSK Investigational Site	Parel		India	400012
3	GSK Investigational Site	Cambridge	Cambridgeshire	United Kingdom	CB2 2QQ
4	GSK Investigational Site	Oxford	Oxfordshire	United Kingdom	OX3 7LJ
5	GSK Investigational Site	Sutton	Surrey	United Kingdom	SM2 5PT