Study Of Sunitinib Plus FOLFOX In Patients With Solid Tumors

Neoplasms Clinical Trial

Official title:

Phase I Study Of SU011248 In Combination With Oxaliplatin, Leucovorin, And 5-Fluorouracil In Patients With Advanced Solid Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00599924
• Other study ID #: A6181048
• Status: Completed
• Phase: Phase 1
• First received: January 11, 2008
• Last updated: June 22, 2015
• Start date: September 2005
• Est. completion date: November 2008

Study information

• Verified date: June 2015
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study determined the maximum tolerated dose and safety of SU011248 (sunitinib malate, SUTENT) in combination with FOLFOX [Leucovorin + Fluorouracil (5-FU) + Oxaliplatin]. Three different dosing regimens with starting doses of sunitinib at 37.5 mg/day (Schedule 2/2, Schedule 4/2, and Continuous Dosing) were tested in patients with advanced solid tumors, including colorectal cancer.

Description:

Study Design: Treatment, Single Group Assignment (7 cohorts), Open Label, Non-Randomized, Safety Study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: November 2008
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Advanced solid tumor malignancy (during expansion at the maximum tolerated dose, entry will be limited to patients wtih adenocarcinoma of the colon or rectum)

• Eastern Cooperative Oncology Group (ECOG) 0 or 1

Exclusion Criteria:

• Prior treatment with more than 6 cycles of traditional alkylating agent-based chemotherapy regimens

• Prior treatment with more than 2 cycles of carboplating-based chemotherapy regimens

• For colorectal cancer patients in the expanded cohorts, prior treatment with more than 2 systemic chemotherapy regimens in the metastatic setting

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Neoplasms

Intervention

Drug:
• sunitinib + FOLFOX
37.5 mg sunitinib + modified FOLFOX6 (Schedule 2/2)
• sunitinib + FOLFOX
50 mg sunitinib + modified FOLFOX6 (Schedule 2/2)
• sunitinib + FOLFOX
50 mg sunitinib + modified FOLFOX6 ( CRC, only Schedule 2/2)
• sunitinib + FOLFOX
37.5 mg sunitinib + modified FOLFOX6 (Schedule 4/2)
• sunitinib + FOLFOX
50 mg sunitinib + modified FOLFOX6 (Schedule 4/2)
• sunitinib + FOLFOX
37.5 mg sunitinib + modified FOLFOX6 (Continuous Dosing)
• sunitinib + FOLFOX
25 mg sunitinib + modified FOLFOX6 (Continuous Dosing)

Locations

Country	Name	City	State
United States	Pfizer Investigational Site	Aurora	Colorado
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)	All observed or volunteered AEs and SAEs regardless of treatment group or suspected causal relationship to the investigational product(s) were reported.	up to 20 weeks	Yes
Secondary	Objective Response (OR)	From the start of treatment until disease progression/recurrence. OR=confirmed Complete Response (CR) or confirmed Partial Response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR = disappearance of all target lesions. CR was confirmed if it persisted on repeat imaging study = 4 weeks after initial documentation of response. PR = = 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. PR was confirmed if it persisted on repeat imaging study = 4 weeks after initial documentation of response.	From start of treatment until Day 8 of Cycles 4 and 8 (2/2 Schedule), Day 8 of Cycles 3 and 6 (4/2 Schedule), and Day 1 of Cycles 3 and 7 (Continuous Dosing)	No
Secondary	Maximum Plasma Concentration (Cmax) of Sunitinib		pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose	No
Secondary	Time to Cmax (Tmax) of Sunitinib		pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose	No
Secondary	Minimum Plasma Concentration (Cmin) of Sunitinib		pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose	No
Secondary	Clearance (CL/F) of Sunitinib	Drug clearance (CL/F) = dose divided by area under the plasma concentration-time profile from time zero to twenty-four hours.	pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose	No
Secondary	Area Under Plasma Concentration-Time Profile From Time Zero to Twenty-Four Hours Postdose (AUC24) of Sunitinib	AUC24 = Area under the plasma concentration-time profile from time zero (pre-dose) to twenty-four hours. AUC24 was obtained by the Linear/Log trapezoidal method.	pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose	No
Secondary	Terminal Phase Half-Life (t1/2) of Sunitinib	t1/2 = terminal phase half-life. t1/2 was obtained by natural log of 2 (ln2) divided by the rate constant for terminal phase (kel).	pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose	No
Secondary	Cmax of SU-012662 (Sunitinib's Metabolite)		pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose	No
Secondary	Tmax of SU-012662 (Sunitinib's Metabolite)		pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose	No
Secondary	Cmin of SU-012662 (Sunitinib's Metabolite)		pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose	No
Secondary	AUC24 for SU-012662 (Sunitinib's Metabolite)	AUC24 = Area under the plasma concentration-time profile from time zero (pre-dose) to twenty-four hours. AUC24 was obtained by the Linear/Log trapezoidal method.	pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose.	No
Secondary	CL/F of SU-012662 (Sunitinib's Metabolite)	CL/F = dose divided by area under the plasma concentration-time profile from time zero to twenty-four hours.	pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose	No
Secondary	T1/2 of SU-012662 (Sunitinib's Metabolite)	t1/2 = terminal phase half-life. t1/2 was obtained by ln2 divided by kel.	pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose	No
Secondary	Cmax of Free Platinum	Oxaliplatin was metabolized to platinum and free platinum was measured.	pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose	No
Secondary	Tmax of Free Platinum	Oxaliplatin was metabolized to platinum and free platinum was measured.	pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose	No
Secondary	Area Under the Plasma Concentration-Time Profile From Time Zero to Infinity (AUCinf) for Free Platinum	Oxaliplatin was metabolized to platinum and free platinum was measured. AUCinf = Area under the plasma concentration-time profile from time zero (pre-dose) to infinity. AUCinf was obtained by the Linear/Log trapezoidal method.	pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose	No
Secondary	T1/2 for Free Platinum	t1/2 = terminal phase half-life. t1/2 was obtained by ln2 divided by kel. Oxaliplatin was metabolized to platinum and free platinum was measured.	pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose	No
Secondary	Cmax of Total Platinum	Oxaliplatin was metabolized to platinum and total platinum was measured.	pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose	No
Secondary	Tmax of Total Platinum	Oxaliplatin was metabolized to platinum and total platinum was measured.	pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose	No
Secondary	Area Under the Plasma Concentration-Time Profile From Time Zero to Forty-Eight Hours (AUC48) for Total Platinum	Oxaliplatin was metabolized to platinum and total platinum was measured. AUC48 = Area under the plasma concentration-time profile from time zero (pre-dose) to forty-eight hours. AUC48 was obtained by the Linear/Log trapezoidal method.	pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose	No
Secondary	Steady State Concentration (Css) of Fluorouracil (5-FU)	Steady state is reached when the amount of drug getting into the system per unit time is equal to the amount of drug cleared from the system.	pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose	No
Secondary	Steady State Clearance (CLss) of 5-FU	CLss was determined by total amount of drug received during infusion or duration of infusion (Ki) divided by Css.	pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose	No
Secondary	Area Under the Curve (AUC) of 5-FU		pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose	No
Secondary	Cmax of 5-FU		pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose	No
Secondary	T1/2 of Free Platinum, Total Platinum, and 5-FU	t1/2 = terminal phase half-life. t1/2 was obtained by ln2 divided by kel. Oxaliplatin was metabolized to platinum and free and total platinum were measured.	pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose	No
Secondary	CL/F of Free Platinum, Total Platinum, and 5-FU	CL/F = dose divided by area under the plasma concentration-time profile from time zero to twenty-four hours.	pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose	No
Secondary	Cmin of Free Platinum, Total Platinum, and 5-FU		pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose	No
Secondary	Volume Endothelial Transfer Constant (Ktrans) of Tumors in a Selected Group of Subjects Assessed by Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI)	Volume endothelial Ktrans was estimated by fitting the tissue contrast agent time course to the Kety equation (Tofts model for analysis of DCE-MRI data).	Cycle 3 (Day 1), Cycle 3 (Day 8)	No
Secondary	Initial Area Dnder the Contrast Agent Concentration-Time Curve (IAUC) of Tumors in a Selected Group of Subjects Assessed by DCE-MRI	IAUC: The initial area under the curve was estimated by integrating the area under the contrast agent concentration time course for the first 90 seconds after bolus arrival in the tumor.	Cycle 3 (Day 1) and Cycle 3 (Day 8)	No

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