Investigational Agent AG-013736 In Combinations With Standard Of Care Treatments For Patient's With Advanced Solid Tumor

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Pfizer

ClinicalTrials.gov Identifier:

NCT00454649

First received: March 29, 2007

Last updated: March 30, 2012

Last verified: March 2012

History of Changes

Purpose

To determine the best dose of this investigational agent AG-013736 in combination with various standard of care treatments for advanced solid tumors.

Condition	Intervention	Phase
Neoplasms	Drug: Axitinib + Paclitaxel + Carboplatin (Cohort 1) Drug: Axitinib + Paclitaxel + Carboplatin (Cohort 2) Drug: Axitinib + Paclitaxel + Carboplatin (Cohort 3) Drug: Axitinib + Paclitaxel (Cohort 4) Drug: Axitinib + Docetaxel + Carboplatin (Cohort 4a) Drug: Axitinib + Docetaxel (Cohort 5) Drug: Axitinib + Capecitabine (Cohort 6) Drug: Axitinib + Capecitabine (Cohort 7) Drug: Axitinib + Gemcitabine + Cisplatin (Cohort 8) Drug: Axitinib + Pemetrexed + Cisplatin (Cohort 9)	Phase 1


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 1 Dose-Finding Study Of The Anti-Angiogenesis Agent, AG-013736, In Combinations Of Paclitaxel/Carboplatin, Weekly Paclitaxel, Docetaxel, Capecitabine, Gemcitabine/Cisplatin and Pemetrexed/Cisplatin In Patients With Advanced Solid Tumors

Resource links provided by NLM:

Drug Information available for: Axitinib

U.S. FDA Resources

Further study details as provided by Pfizer:

Primary Outcome Measures:

Maximum Tolerated Dose (MTD) of Axitinib (AG-013736) in Combination With Chemotherapy [ Time Frame: Baseline to withdrawal from study or Day 21 of Cycle 1 [all cohorts except cohort 4 (Day 28 of Cycle 1)] ]
MTD defined as the dose level at which more than 1 out of 6 participants experienced a dose limiting toxicity (DLT). DLT included grade (Gr) 4 neutropenia or thrombocytopenia, greater than or equal to (>=) Gr 3 nonhematological toxicities or >=0.5 teaspoon/day hemoptysis or >=2 gram /24 hours proteinuria or inability to resume background chemotherapy or axitinib (AG-013736) dosing within 14 days of stopping due to treatment related toxicity.

Secondary Outcome Measures:

Area Under the Curve From Time Zero to Time 24 Hours [AUC (0-24)] for Axitinib (AG-013736) [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 6, 8 hr post-dose on Day -1 for cohort 1, 2, 3, 5 and 8; on Day 22 of Cycle 1 for cohort 4; on Day 18 of Cycle 1 for cohorts 6 and 7; 0 (pre-dose), 1.2, 2.2, 3.2, 4.2, 6.2, 8.2 hr post-dose on Day -1 for cohort 9 ]
AUC (0-24) = Area under the plasma concentration versus time curve from time zero (pre-dose) to time 24 hours (0-24).
Maximum Observed Plasma Concentration (Cmax) for Axitinib (AG-013736) [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 6, 8 hr post-dose on Day -1 for cohort 1, 2, 3, 5 and 8; on Day 22 of Cycle 1 for cohort 4; on Day 18 of Cycle 1 for cohorts 6 and 7; 0 (pre-dose), 1.2, 2.2, 3.2, 4.2, 6.2, 8.2 hr post-dose on Day -1 for cohort 9 ]
Minimum Observed Plasma Trough Concentration (Cmin) for Axitinib (AG-013736) [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 6, 8 hr post-dose on Day -1 for cohort 1, 2, 3, 5 and 8; on Day 22 of Cycle 1 for cohort 4; on Day 18 of Cycle 1 for cohorts 6 and 7; 0 (pre-dose), 1.2, 2.2, 3.2, 4.2, 6.2, 8.2 hr post-dose on Day -1 for cohort 9 ]
Apparent Oral Clearance (CL/F) for Axitinib (AG-013736) [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 6, 8 hr post-dose on Day -1 for cohort 1, 2, 3, 5 and 8; on Day 22 of Cycle 1 for cohort 4; on Day 18 of Cycle 1 for cohorts 6 and 7; 0 (pre-dose), 1.2, 2.2, 3.2, 4.2, 6.2, 8.2 hr post-dose on Day -1 for cohort 9 ]
Clearance (CL) of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes and F is the absolute oral bioavailability. Apparent oral clearance(CL/F) is obtained following oral administration.
Plasma Decay Half Life (t1/2) for Axitinib (AG-013736) [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 6, 8 hr post-dose on Day -1 for cohort 1, 2, 3, 5 and 8; on Day 22 of Cycle 1 for cohort 4; on Day 18 of Cycle 1 for cohorts 6 and 7; 0 (pre-dose), 1.2, 2.2, 3.2, 4.2, 6.2, 8.2 hr post-dose on Day -1 for cohort 9 ]
t1/2 is the time measured for the plasma concentration to decrease by one half.
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Paclitaxel [ Time Frame: 0 (pre-dose), 1, 2, 3, 3.25, 3.5, 4, 5, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 1-3; 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 4 ]
AUC (0-∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞).
Maximum Observed Plasma Concentration (Cmax) for Paclitaxel [ Time Frame: 0 (pre-dose), 1, 2, 3, 3.25, 3.5, 4, 5, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 1-3; 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 4 ]
Minimum Observed Plasma Trough Concentration (Cmin) for Paclitaxel [ Time Frame: 0 (pre-dose), 1, 2, 3, 3.25, 3.5, 4, 5, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 1-3; 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 4 ]
Plasma Clearance (CL) for Paclitaxel [ Time Frame: 0 (pre-dose), 1, 2, 3, 3.25, 3.5, 4, 5, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 1-3; 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 4 ]
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the plasma.
Plasma Decay Half Life (t1/2) for Paclitaxel [ Time Frame: 0 (pre-dose), 1, 2, 3, 3.25, 3.5, 4, 5, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 1-3; 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 4 ]
t1/2 is the time measured for the plasma concentration to decrease by one half.
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Docetaxel [ Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 5 ]
AUC (0-∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞).
Maximum Observed Plasma Concentration (Cmax) for Docetaxel [ Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 5 ]
Minimum Observed Plasma Trough Concentration (Cmin) for Docetaxel [ Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 5 ]
Plasma Clearance (CL) for Docetaxel [ Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 5 ]
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the plasma.
Plasma Decay Half Life (t1/2) for Docetaxel [ Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 5 ]
t1/2 is the time measured for the plasma concentration to decrease by one half.
Area Under the Curve From Time Zero to Time 24 Hours [AUC (0-24)] for Capecitabine [ Time Frame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 hr post-dose on Day 1 of Cycle 2 for cohort 6 and 7 ]
AUC (0-24) = Area under the plasma concentration versus time curve from time zero (pre-dose) to time 24 hours (0-24).
Maximum Observed Plasma Concentration (Cmax) for Capecitabine [ Time Frame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 hr post-dose on Day 1 of Cycle 2 for cohort 6 and 7 ]
Minimum Observed Plasma Trough Concentration (Cmin) for Capecitabine [ Time Frame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 hr post-dose on Day 1 of Cycle 2 for cohort 6 and 7 ]
Apparent Oral Clearance (CL/F) for Capecitabine [ Time Frame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 hr post-dose on Day 1 of Cycle 2 for cohort 6 and 7 ]
Clearance (CL) of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes and F is the absolute oral bioavailability. Apparent oral clearance(CL/F) is obtained following oral administration.
Plasma Decay Half Life (t1/2) for Capecitabine [ Time Frame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 hr post-dose on Day 1 of Cycle 2 for cohort 6 and 7 ]
t1/2 is the time measured for the plasma concentration to decrease by one half.
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Gemcitabine [ Time Frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4 hr after start of infusion on Day 1 of Cycle 2 for cohort 8 ]
AUC (0-∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞).
Maximum Observed Plasma Concentration (Cmax) for Gemcitabine [ Time Frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4 hr after start of infusion on Day 1 of Cycle 2 for cohort 8 ]
Minimum Observed Plasma Trough Concentration (Cmin) for Gemcitabine [ Time Frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4 hr after start of infusion on Day 1 of Cycle 2 for cohort 8 ]
Plasma Clearance (CL) for Gemcitabine [ Time Frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4 hr after start of infusion on Day 1 of Cycle 2 for cohort 8 ]
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the plasma.
Plasma Decay Half Life (t1/2) for Gemcitabine [ Time Frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4 hr after start of infusion on Day 1 of Cycle 2 for cohort 8 ]
t1/2 is the time measured for the plasma concentration to decrease by one half.
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Carboplatin [ Time Frame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 5 hr after start of infusion on Day 1 of Cycle 2 for cohort 1-3 ]
AUC (0-∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞).
Maximum Observed Plasma Concentration (Cmax) for Carboplatin [ Time Frame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 5 hr after start of infusion on Day 1 of Cycle 2 for cohort 1-3 ]
Minimum Observed Plasma Trough Concentration (Cmin) for Carboplatin [ Time Frame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 5 hr after start of infusion on Day 1 of Cycle 2 for cohort 1-3 ]
Plasma Clearance (CL) for Carboplatin [ Time Frame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 5 hr after start of infusion on Day 1 of Cycle 2 for cohort 1-3 ]
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the plasma.
Plasma Decay Half Life (t1/2) for Carboplatin [ Time Frame: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 5 hr after start of infusion on Day 1 of Cycle 2 for cohort 1-3 ]
t1/2 is the time measured for the plasma concentration to decrease by one half.
Area Under the Curve From Time Zero to Time 8 Hours [AUC (0-8)] for Cisplatin [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 7 hr after start of infusion on Day 1 of Cycle 2 for cohort 8 and 9 ]
AUC (0-8) = Area under the plasma concentration versus time curve from time zero (pre-dose) to time 8 hours (0-8).
Maximum Observed Plasma Concentration (Cmax) for Cisplatin [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 7 hr after start of infusion on Day 1 of Cycle 2 for cohort 8 and 9 ]
Minimum Observed Plasma Trough Concentration (Cmin) for Cisplatin [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 7 hr after start of infusion on Day 1 of Cycle 2 for cohort 8 and 9 ]
Plasma Clearance (CL) for Cisplatin [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 7 hr after start of infusion on Day 1 of Cycle 2 for cohort 8 and 9 ]
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the plasma.
Plasma Decay Half Life (t1/2) for Cisplatin [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 7 hr after start of infusion on Day 1 of Cycle 2 for cohort 8 and 9 ]
t1/2 is the time measured for the plasma concentration to decrease by one half.
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Pemetrexed [ Time Frame: 0 (pre-dose), 10 minutes (end of infusion), 0.5, 1, 1.5, 2, 4, 6, 8 hr after end of infusion on Day 1 of Cycle 2 for cohort 9 ]
AUC (0-∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞).
Maximum Observed Plasma Concentration (Cmax) for Pemetrexed [ Time Frame: 0 (pre-dose), 10 minutes (end of infusion), 0.5, 1, 1.5, 2, 4, 6, 8 hr after end of infusion on Day 1 of Cycle 2 for cohort 9 ]
Minimum Observed Plasma Trough Concentration (Cmin) for Pemetrexed [ Time Frame: 0 (pre-dose), 10 minutes (end of infusion), 0.5, 1, 1.5, 2, 4, 6, 8 hr after end of infusion on Day 1 of Cycle 2 for cohort 9 ]
Plasma Clearance (CL) for Pemetrexed [ Time Frame: 0 (pre-dose), 10 minutes (end of infusion), 0.5, 1, 1.5, 2, 4, 6, 8 hr after end of infusion on Day 1 of Cycle 2 for cohort 9 ]
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the plasma.
Plasma Decay Half Life (t1/2) for Pemetrexed [ Time Frame: 0 (pre-dose), 10 minutes (end of infusion), 0.5, 1, 1.5, 2, 4, 6, 8 hr after end of infusion on Day 1 of Cycle 2 for cohort 9 ]
t1/2 is the time measured for the plasma concentration to decrease by one half.
Percentage of Participants With Objective Response [ Time Frame: Baseline and thereafter every 2 cycles up to disease progression or discontinuation from study or up to 155 weeks ]
Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. Confirmed response are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR are defined as the disappearance of all lesions (target and/or non target). PR are those with at least 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.


Enrollment:	102
Study Start Date:	December 2005
Study Completion Date:	April 2011
Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Axitinib [AG-013736] + chemotherapy combination The following separate groups were included: axitinib plus carboplatin/paclitaxel in three different schedules plus paclitaxel plus docetaxel/carboplatin plus docetaxel plus capecitabine plus gemcitabine/cisplatin plus pemetrexed/cisplatin	Drug: Axitinib + Paclitaxel + Carboplatin (Cohort 1) Axitinib (AG-013736) 1 milligram (mg) tablet orally twice daily (BID) as lead in dose from Day -5, -4 or -3 through Day 2 of Cycle 1 (21 days). Axitinib (AG-013736) 5 mg tablet orally BID from Day 3 to Day 18 of Cycle 1 and Day 3 to Day 20 of Cycle 2 (21 days) and all subsequent cycles (21 days). Paclitaxel [200 milligram/square meter (mg/m^2)] 3-hour infusion followed by carboplatin 30-minutes infusion at a dose to target area under the concentration-time curve (AUC) of 6.0 milligramminute/milliliter (mgmin/mL) on Day 1 of Cycle 1 and all subsequent cycles. Drug: Axitinib + Paclitaxel + Carboplatin (Cohort 2) Axitinib (AG-013736) 3 tablets of 1 mg orally BID as lead in dose from Day -5, -4 or -3 through Day 2 of Cycle 1 (21 days). Axitinib (AG-013736) 5 mg tablet orally BID from Day 3 to Day 18 of Cycle 1 and Day 3 to Day 20 of Cycle 2 (21 days) and all subsequent cycles (21 days). Paclitaxel (200 mg/m^2) 3-hour infusion followed by carboplatin 30-minutes infusion at a dose to target AUC of 6.0 mgmin/mL on Day 1 of Cycle 1 and all subsequent cycles. Drug: Axitinib + Paclitaxel + Carboplatin (Cohort 3) Axitinib (AG-013736) 5 mg tablet orally BID as lead in dose from Day -5, -4 or -3 through Day 2 of Cycle 1 (21 days). Axitinib (AG-013736) 5 mg tablet orally BID from Day 3 to Day 18 of Cycle 1 and Day 3 to Day 20 of Cycle 2 (21 days) and all subsequent cycles (21 days). Paclitaxel (200 mg/m^2) 3-hour infusion followed by carboplatin 30-minutes infusion at a dose to target AUC of 6.0 mgmin/mL on Day 1 of Cycle 1 and all subsequent cycles. Drug: Axitinib + Paclitaxel (Cohort 4) Axitinib (AG-013736) 5 mg tablet orally BID from Day 1 to Day 25 of Cycle 1 (28 days) and then without interruption from Day 3 for Cycle 2 (28 days) and all subsequent cycles (28 days). Paclitaxel (90 mg/m^2) 60-minute infusion on Day 1, 8, and 15 of each cycle. Drug: Axitinib + Docetaxel + Carboplatin (Cohort 4a) Axitinib (AG-013736) 5 mg tablet orally BID as lead in dose from Day -5, -4 or -3 through Day 2 of Cycle 1 (21 days). Axitinib (AG-013736) 5 mg tablet orally BID from Day 3 to Day 18 of Cycle 1 and Day 3 to Day 20 of Cycle 2 (21 days) and all subsequent cycles (21 days). Docetaxel (75 mg/m^2) 60-minute infusion on Day 1 of every cycle. Carboplatin 30-minutes infusion at a dose to target AUC of 6.0 mg*min/mL on Day 1 of Cycle 1 and all subsequent cycles. Drug: Axitinib + Docetaxel (Cohort 5) Axitinib (AG-013736) 5 mg tablet orally BID as lead in dose from Day -5, -4 or -3 through Day 2 of Cycle 1. Axitinib (AG-013736) 5 mg oral tablet BID administered from Day 3 to Day 18 of Cycle 1 (21 days) and then without interruption from Day 3 of Cycle 2 and all subsequent cycles. Docetaxel (100 mg/m^2) 60-minute infusion on Day 1 of each cycle. Drug: Axitinib + Capecitabine (Cohort 6) Axitinib (AG-013736) 5 mg tablet orally BID from Day 1 to Day 18 of Cycle 1 (21 days) and then without interruption from Day 3 of Cycle 2 and all subsequent cycles. Capecitabine (1000 mg/m^2) orally BID from Day 1 to Day 14 of each cycle. Drug: Axitinib + Capecitabine (Cohort 7) Axitinib (AG-013736) 5 mg tablet orally BID from Day 1 to Day 18 of Cycle 1 (21 days) and then without interruption from Day 3 of Cycle 2 and all subsequent cycles. Capecitabine (1250 mg/m^2) orally BID from Day 1 to Day 14 of each cycle. Drug: Axitinib + Gemcitabine + Cisplatin (Cohort 8) Axitinib (AG-013736) 5 mg tablet orally BID from Day -5, -4 or -3 to Day 18 of Cycle 1 (21 days) and then without interruption from Day 3 of Cycle 2 and all subsequent cycles. Gemcitabine (1250 mg/m^2) 30-minute infusion on Day 1 and Day 8 of Cycle 1 and all subsequent cycles followed by cisplatin (80 mg/m^2) infusion on Day 1 of each cycle. Drug: Axitinib + Pemetrexed + Cisplatin (Cohort 9) Axitinib (AG-013736) 5 mg tablet orally BID from Day -5, -4 or -3 to Day 18 of Cycle 1 (21 days) and then without interruption from Day 3 of Cycle 2 and all subsequent cycles. Pemetrexed (500 mg/m^2) 10-minute infusion followed by cisplatin (75 mg/m^2) infusion on Day 1 of each cycle.

Arms

Assigned Interventions

Experimental: Axitinib [AG-013736] + chemotherapy combination

The following separate groups were included:

axitinib

plus carboplatin/paclitaxel in three different schedules
plus paclitaxel
plus docetaxel/carboplatin
plus docetaxel
plus capecitabine
plus gemcitabine/cisplatin
plus pemetrexed/cisplatin

Drug: Axitinib + Paclitaxel + Carboplatin (Cohort 1)

Axitinib (AG-013736) 1 milligram (mg) tablet orally twice daily (BID) as lead in dose from Day -5, -4 or -3 through Day 2 of Cycle 1 (21 days). Axitinib (AG-013736) 5 mg tablet orally BID from Day 3 to Day 18 of Cycle 1 and Day 3 to Day 20 of Cycle 2 (21 days) and all subsequent cycles (21 days). Paclitaxel [200 milligram/square meter (mg/m^2)] 3-hour infusion followed by carboplatin 30-minutes infusion at a dose to target area under the concentration-time curve (AUC) of 6.0 milligram*minute/milliliter (mg*min/mL) on Day 1 of Cycle 1 and all subsequent cycles.

Drug: Axitinib + Paclitaxel + Carboplatin (Cohort 2)

Axitinib (AG-013736) 3 tablets of 1 mg orally BID as lead in dose from Day -5, -4 or -3 through Day 2 of Cycle 1 (21 days). Axitinib (AG-013736) 5 mg tablet orally BID from Day 3 to Day 18 of Cycle 1 and Day 3 to Day 20 of Cycle 2 (21 days) and all subsequent cycles (21 days). Paclitaxel (200 mg/m^2) 3-hour infusion followed by carboplatin 30-minutes infusion at a dose to target AUC of 6.0 mg*min/mL on Day 1 of Cycle 1 and all subsequent cycles.

Drug: Axitinib + Paclitaxel + Carboplatin (Cohort 3)

Axitinib (AG-013736) 5 mg tablet orally BID as lead in dose from Day -5, -4 or -3 through Day 2 of Cycle 1 (21 days). Axitinib (AG-013736) 5 mg tablet orally BID from Day 3 to Day 18 of Cycle 1 and Day 3 to Day 20 of Cycle 2 (21 days) and all subsequent cycles (21 days). Paclitaxel (200 mg/m^2) 3-hour infusion followed by carboplatin 30-minutes infusion at a dose to target AUC of 6.0 mg*min/mL on Day 1 of Cycle 1 and all subsequent cycles.

Drug: Axitinib + Paclitaxel (Cohort 4)

Axitinib (AG-013736) 5 mg tablet orally BID from Day 1 to Day 25 of Cycle 1 (28 days) and then without interruption from Day 3 for Cycle 2 (28 days) and all subsequent cycles (28 days). Paclitaxel (90 mg/m^2) 60-minute infusion on Day 1, 8, and 15 of each cycle.

Drug: Axitinib + Docetaxel + Carboplatin (Cohort 4a)

Axitinib (AG-013736) 5 mg tablet orally BID as lead in dose from Day -5, -4 or -3 through Day 2 of Cycle 1 (21 days). Axitinib (AG-013736) 5 mg tablet orally BID from Day 3 to Day 18 of Cycle 1 and Day 3 to Day 20 of Cycle 2 (21 days) and all subsequent cycles (21 days). Docetaxel (75 mg/m^2) 60-minute infusion on Day 1 of every cycle. Carboplatin 30-minutes infusion at a dose to target AUC of 6.0 mg*min/mL on Day 1 of Cycle 1 and all subsequent cycles.

Drug: Axitinib + Docetaxel (Cohort 5)

Axitinib (AG-013736) 5 mg tablet orally BID as lead in dose from Day -5, -4 or -3 through Day 2 of Cycle 1. Axitinib (AG-013736) 5 mg oral tablet BID administered from Day 3 to Day 18 of Cycle 1 (21 days) and then without interruption from Day 3 of Cycle 2 and all subsequent cycles. Docetaxel (100 mg/m^2) 60-minute infusion on Day 1 of each cycle.

Drug: Axitinib + Capecitabine (Cohort 6)

Axitinib (AG-013736) 5 mg tablet orally BID from Day 1 to Day 18 of Cycle 1 (21 days) and then without interruption from Day 3 of Cycle 2 and all subsequent cycles. Capecitabine (1000 mg/m^2) orally BID from Day 1 to Day 14 of each cycle.

Drug: Axitinib + Capecitabine (Cohort 7)

Axitinib (AG-013736) 5 mg tablet orally BID from Day 1 to Day 18 of Cycle 1 (21 days) and then without interruption from Day 3 of Cycle 2 and all subsequent cycles. Capecitabine (1250 mg/m^2) orally BID from Day 1 to Day 14 of each cycle.

Drug: Axitinib + Gemcitabine + Cisplatin (Cohort 8)

Axitinib (AG-013736) 5 mg tablet orally BID from Day -5, -4 or -3 to Day 18 of Cycle 1 (21 days) and then without interruption from Day 3 of Cycle 2 and all subsequent cycles. Gemcitabine (1250 mg/m^2) 30-minute infusion on Day 1 and Day 8 of Cycle 1 and all subsequent cycles followed by cisplatin (80 mg/m^2) infusion on Day 1 of each cycle.

Drug: Axitinib + Pemetrexed + Cisplatin (Cohort 9)

Axitinib (AG-013736) 5 mg tablet orally BID from Day -5, -4 or -3 to Day 18 of Cycle 1 (21 days) and then without interruption from Day 3 of Cycle 2 and all subsequent cycles. Pemetrexed (500 mg/m^2) 10-minute infusion followed by cisplatin (75 mg/m^2) infusion on Day 1 of each cycle.

Eligibility


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

Criteria

Inclusion Criteria:

Advanced solid tumors suitable for treatment with Taxanes, with or without carboplatin, or treatment with Capecitabine, Gemcitabine/Cisplatin. or Pemetrexed/Cisplatin

Exclusion Criteria:

Tumors abutting or providing support for blood vessels
Any significant gastrointestinal abnormalities or active bleeding.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00454649

Locations


United States, Georgia
Pfizer Investigational Site
Augusta, Georgia, United States, 30909
Pfizer Investigational Site
Augusta, Georgia, United States, 30912
United States, Illinois
Pfizer Investigational Site
Harvey, Illinois, United States, 60426-4265
Pfizer Investigational Site
Harvey, Illinois, United States, 60426
Pfizer Investigational Site
Tinley Park, Illinois, United States, 60477
United States, Indiana
Pfizer Investigational Site
Hobart, Indiana, United States, 46342
Pfizer Investigational Site
Munster, Indiana, United States, 46321
United States, Pennsylvania
Pfizer Investigational Site
Philadelphia, Pennsylvania, United States, 19111
United States, Texas
Pfizer Investigational Site
Houston, Texas, United States, 77030-4009
United States, Washington
Pfizer Investigational Site
Kennewick, Washington, United States, 99336
Poland
Pfizer Investigational Site
Warszawa, Poland, 02-781
Spain
Pfizer Investigational Site
Barcelona, Spain, 08003
Pfizer Investigational Site
Madrid, Spain, 28046

Sponsors and Collaborators

Pfizer

Investigators


Study Director:	Pfizer CT.gov Call Center	Pfizer

More Information

Additional Information:

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Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT00454649 History of Changes
Other Study ID Numbers:	A4061019
Study First Received:	March 29, 2007
Results First Received:	February 25, 2012
Last Updated:	March 30, 2012

Keywords provided by Pfizer:


axitinib chemotherapy anti-angiogenesis VEGF inhibition

Additional relevant MeSH terms:


Paclitaxel Docetaxel Gemcitabine Albumin-Bound Paclitaxel Capecitabine Cisplatin Carboplatin Pemetrexed Axitinib Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents	Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Antimetabolites Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Folic Acid Antagonists Nucleic Acid Synthesis Inhibitors Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on June 23, 2017

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