To determine the best dose of this investigational agent AG-013736 in combination with various standard of care treatments for advanced solid tumors.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
102
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.
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.
Pfizer Investigational Site
Augusta, Georgia, United States
Pfizer Investigational Site
Augusta, Georgia, United States
Pfizer Investigational Site
Harvey, Illinois, United States
Maximum Tolerated Dose (MTD) of Axitinib (AG-013736) in Combination With Chemotherapy
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.
Time frame: Baseline to withdrawal from study or Day 21 of Cycle 1 [all cohorts except cohort 4 (Day 28 of Cycle 1)]
Area Under the Curve From Time Zero to Time 24 Hours [AUC (0-24)] for Axitinib (AG-013736)
AUC (0-24) = Area under the plasma concentration versus time curve from time zero (pre-dose) to time 24 hours (0-24).
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
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)
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.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
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.
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.
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.
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.
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.
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.
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.
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.
Pfizer Investigational Site
Harvey, Illinois, United States
Pfizer Investigational Site
Tinley Park, Illinois, United States
Pfizer Investigational Site
Hobart, Indiana, United States
Pfizer Investigational Site
Munster, Indiana, United States
Pfizer Investigational Site
Philadelphia, Pennsylvania, United States
Pfizer Investigational Site
Houston, Texas, United States
Pfizer Investigational Site
Kennewick, Washington, United States
...and 3 more locations
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
Plasma Decay Half Life (t1/2) for Axitinib (AG-013736)
t1/2 is the time measured for the plasma concentration to decrease by one half.
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
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Paclitaxel
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-∞).
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
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
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.
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 Decay Half Life (t1/2) for Paclitaxel
t1/2 is the time measured for the plasma concentration to decrease by one half.
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
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Docetaxel
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-∞).
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
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
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.
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 Decay Half Life (t1/2) for Docetaxel
t1/2 is the time measured for the plasma concentration to decrease by one half.
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
Area Under the Curve From Time Zero to Time 24 Hours [AUC (0-24)] for Capecitabine
AUC (0-24) = Area under the plasma concentration versus time curve from time zero (pre-dose) to time 24 hours (0-24).
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
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
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.
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
Plasma Decay Half Life (t1/2) for Capecitabine
t1/2 is the time measured for the plasma concentration to decrease by one half.
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
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Gemcitabine
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-∞).
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
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
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.
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 Decay Half Life (t1/2) for Gemcitabine
t1/2 is the time measured for the plasma concentration to decrease by one half.
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
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Carboplatin
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-∞).
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
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
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.
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 Decay Half Life (t1/2) for Carboplatin
t1/2 is the time measured for the plasma concentration to decrease by one half.
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
Area Under the Curve From Time Zero to Time 8 Hours [AUC (0-8)] for Cisplatin
AUC (0-8) = Area under the plasma concentration versus time curve from time zero (pre-dose) to time 8 hours (0-8).
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
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
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.
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 Decay Half Life (t1/2) for Cisplatin
t1/2 is the time measured for the plasma concentration to decrease by one half.
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
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Pemetrexed
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-∞).
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
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
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.
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 Decay Half Life (t1/2) for Pemetrexed
t1/2 is the time measured for the plasma concentration to decrease by one half.
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
Percentage of Participants With Objective Response
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.
Time frame: Baseline and thereafter every 2 cycles up to disease progression or discontinuation from study or up to 155 weeks