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

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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00454649

Enrollment

102

Registered

2007-04-02

Start date

2005-12-31

Completion date

2011-04-30

Last updated

2012-04-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Neoplasms

Keywords

axitinib, chemotherapy, anti-angiogenesis, VEGF inhibition

Brief summary

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

Interventions

DRUGAxitinib + 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.

DRUGAxitinib + 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.

DRUGAxitinib + 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.

DRUGAxitinib + 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.

DRUGAxitinib + 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.

DRUGAxitinib + 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.

DRUGAxitinib + 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.

DRUGAxitinib + 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.

DRUGAxitinib + 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.

DRUGAxitinib + 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.

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Maximum Tolerated Dose (MTD) of Axitinib (AG-013736) in Combination With Chemotherapy	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

Measure	Time frame	Description
Maximum Observed Plasma Concentration (Cmax) for Axitinib (AG-013736)	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)	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)	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)	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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-∞).
Area Under the Curve From Time Zero to Time 24 Hours [AUC (0-24)] for Axitinib (AG-013736)	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).
Minimum Observed Plasma Trough Concentration (Cmin) for Pemetrexed	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	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	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	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.
Maximum Observed Plasma Concentration (Cmax) for Pemetrexed	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	—

Countries

Poland, Spain, United States

Participant flow

Pre-assignment details

A total of 102 participants were enrolled for the study. Out of those, 4 participants were screen failure and were not included in results analysis.

Participants by arm

Arm	Count
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.	3
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.	5
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.	20
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.	7
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.	1
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.	7
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.	9
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.	19
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.	21
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.	6
Total	98

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007	FG008	FG009
Overall Study	Adverse Event	0	1	3	0	1	2	3	4	6	2
Overall Study	Lack of Efficacy	2	2	10	3	0	4	5	13	10	2
Overall Study	Lost to Follow-up	0	0	1	0	0	0	1	0	0	0
Overall Study	Other	1	1	5	3	0	0	0	0	3	1
Overall Study	Withdrawal by Subject	0	0	0	0	0	1	0	2	1	0

Baseline characteristics

Characteristic	Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Axitinib + Paclitaxel + Carboplatin (Cohort 2)	Axitinib + Paclitaxel + Carboplatin (Cohort 3)	Axitinib + Paclitaxel (Cohort 4)	Axitinib + Docetaxel + Carboplatin (Cohort 4a)	Axitinib + Docetaxel (Cohort 5)	Axitinib + Capecitabine (Cohort 6)	Axitinib + Capecitabine (Cohort 7)	Axitinib + Gemcitabine + Cisplatin (Cohort 8)	Axitinib + Pemetrexed + Cisplatin (Cohort 9)	Total
Age Continuous	61 years STANDARD_DEVIATION 11.4	62 years STANDARD_DEVIATION 16.6	59.5 years STANDARD_DEVIATION 10.6	60.7 years STANDARD_DEVIATION 10.2	64 years	63.4 years STANDARD_DEVIATION 11.9	60.4 years STANDARD_DEVIATION 12.4	53.4 years STANDARD_DEVIATION 10.6	54 years STANDARD_DEVIATION 10.3	58.8 years STANDARD_DEVIATION 9	57.8 years STANDARD_DEVIATION 11.1
Sex: Female, Male Female	2 Participants	2 Participants	3 Participants	3 Participants	1 Participants	5 Participants	5 Participants	11 Participants	12 Participants	3 Participants	47 Participants
Sex: Female, Male Male	1 Participants	3 Participants	17 Participants	4 Participants	0 Participants	2 Participants	4 Participants	8 Participants	9 Participants	3 Participants	51 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	3 / 3	5 / 5	20 / 20	7 / 7	1 / 1	7 / 7	9 / 9	19 / 19	21 / 21	6 / 6
serious Total, serious adverse events	2 / 3	2 / 5	11 / 20	2 / 7	1 / 1	4 / 7	6 / 9	9 / 19	13 / 21	4 / 6

Outcome results

Primary

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)]

Population: Safety analysis population included all enrolled participants who received at least 1 dose of study medication.

Arm	Measure	Value (NUMBER)
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Maximum Tolerated Dose (MTD) of Axitinib (AG-013736) in Combination With Chemotherapy	5 mg BID
Axitinib + Paclitaxel + Carboplatin (Cohort 2)	Maximum Tolerated Dose (MTD) of Axitinib (AG-013736) in Combination With Chemotherapy	5 mg BID
Axitinib + Paclitaxel + Carboplatin (Cohort 3)	Maximum Tolerated Dose (MTD) of Axitinib (AG-013736) in Combination With Chemotherapy	5 mg BID
Axitinib + Paclitaxel (Cohort 4)	Maximum Tolerated Dose (MTD) of Axitinib (AG-013736) in Combination With Chemotherapy	5 mg BID
Axitinib + Docetaxel (Cohort 5)	Maximum Tolerated Dose (MTD) of Axitinib (AG-013736) in Combination With Chemotherapy	NA mg BID
Axitinib + Capecitabine (Cohort 6)	Maximum Tolerated Dose (MTD) of Axitinib (AG-013736) in Combination With Chemotherapy	5 mg BID
Axitinib + Capecitabine (Cohort 7)	Maximum Tolerated Dose (MTD) of Axitinib (AG-013736) in Combination With Chemotherapy	5 mg BID
Axitinib + Gemcitabine + Cisplatin (Cohort 8)	Maximum Tolerated Dose (MTD) of Axitinib (AG-013736) in Combination With Chemotherapy	5 mg BID
Axitinib + Pemetrexed + Cisplatin (Cohort 9)	Maximum Tolerated Dose (MTD) of Axitinib (AG-013736) in Combination With Chemotherapy	5 mg BID

Secondary

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.

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

Population: The pharmacokinetic parameter analysis set included all treated participants who had at least 1 estimated pharmacokinetic parameter of primary interest. N (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Apparent Oral Clearance (CL/F) for Axitinib (AG-013736)	49.39 Liter/hour (L/hr)	Standard Deviation 34.46
Axitinib + Paclitaxel + Carboplatin (Cohort 2)	Apparent Oral Clearance (CL/F) for Axitinib (AG-013736)	40.72 Liter/hour (L/hr)	Standard Deviation 46.75
Axitinib + Paclitaxel + Carboplatin (Cohort 3)	Apparent Oral Clearance (CL/F) for Axitinib (AG-013736)	29.73 Liter/hour (L/hr)	Standard Deviation 18.49
Axitinib + Paclitaxel (Cohort 4)	Apparent Oral Clearance (CL/F) for Axitinib (AG-013736)	65.69 Liter/hour (L/hr)	Standard Deviation 11.94
Axitinib + Docetaxel (Cohort 5)	Apparent Oral Clearance (CL/F) for Axitinib (AG-013736)	14.35 Liter/hour (L/hr)	Standard Deviation 7.67
Axitinib + Capecitabine (Cohort 6)	Apparent Oral Clearance (CL/F) for Axitinib (AG-013736)	26.64 Liter/hour (L/hr)	Standard Deviation 15.58
Axitinib + Capecitabine (Cohort 7)	Apparent Oral Clearance (CL/F) for Axitinib (AG-013736)	83.46 Liter/hour (L/hr)	Standard Deviation 171.05
Axitinib + Gemcitabine + Cisplatin (Cohort 8)	Apparent Oral Clearance (CL/F) for Axitinib (AG-013736)	50.05 Liter/hour (L/hr)	Standard Deviation 56.75
Axitinib + Pemetrexed + Cisplatin (Cohort 9)	Apparent Oral Clearance (CL/F) for Axitinib (AG-013736)	25.10 Liter/hour (L/hr)	Standard Deviation 21.31

Secondary

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

Arm	Measure	Value (MEAN)	Dispersion
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Apparent Oral Clearance (CL/F) for Capecitabine	209.05 Liter/hr	Standard Deviation 24.29
Axitinib + Paclitaxel + Carboplatin (Cohort 2)	Apparent Oral Clearance (CL/F) for Capecitabine	314.12 Liter/hr	Standard Deviation 247.27

Secondary

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

Arm	Measure	Value (MEAN)	Dispersion
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Carboplatin	55580.26 ng*hr/mL	Standard Deviation 9689.44

Secondary

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

Arm	Measure	Value (MEAN)	Dispersion
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Docetaxel	3478.49 ng*hr/mL	Standard Deviation 870.12

Secondary

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

Arm	Measure	Value (MEAN)	Dispersion
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Gemcitabine	10991.16 ng*hr/mL	Standard Deviation 3099.28

Secondary

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

Arm	Measure	Value (MEAN)	Dispersion
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Paclitaxel	5683.55 ng*hr/mL	Standard Deviation 1519.49
Axitinib + Paclitaxel + Carboplatin (Cohort 2)	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Paclitaxel	19959.91 ng*hr/mL	Standard Deviation 5951.86

Secondary

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

Arm	Measure	Value (MEAN)	Dispersion
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Pemetrexed	133032.97 ng*hr/mL	Standard Deviation 40176.65

Secondary

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).

Arm	Measure	Value (MEAN)	Dispersion
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Area Under the Curve From Time Zero to Time 24 Hours [AUC (0-24)] for Axitinib (AG-013736)	61.58 nanogramhour/milliliter (nghr/mL)	Standard Deviation 54.66
Axitinib + Paclitaxel + Carboplatin (Cohort 2)	Area Under the Curve From Time Zero to Time 24 Hours [AUC (0-24)] for Axitinib (AG-013736)	242.41 nanogramhour/milliliter (nghr/mL)	Standard Deviation 132.24
Axitinib + Paclitaxel + Carboplatin (Cohort 3)	Area Under the Curve From Time Zero to Time 24 Hours [AUC (0-24)] for Axitinib (AG-013736)	475.18 nanogramhour/milliliter (nghr/mL)	Standard Deviation 380.13
Axitinib + Paclitaxel (Cohort 4)	Area Under the Curve From Time Zero to Time 24 Hours [AUC (0-24)] for Axitinib (AG-013736)	154.43 nanogramhour/milliliter (nghr/mL)	Standard Deviation 28.93
Axitinib + Docetaxel (Cohort 5)	Area Under the Curve From Time Zero to Time 24 Hours [AUC (0-24)] for Axitinib (AG-013736)	780.99 nanogramhour/milliliter (nghr/mL)	Standard Deviation 535.3
Axitinib + Capecitabine (Cohort 6)	Area Under the Curve From Time Zero to Time 24 Hours [AUC (0-24)] for Axitinib (AG-013736)	365.95 nanogramhour/milliliter (nghr/mL)	Standard Deviation 143.13
Axitinib + Capecitabine (Cohort 7)	Area Under the Curve From Time Zero to Time 24 Hours [AUC (0-24)] for Axitinib (AG-013736)	449.99 nanogramhour/milliliter (nghr/mL)	Standard Deviation 323.59
Axitinib + Gemcitabine + Cisplatin (Cohort 8)	Area Under the Curve From Time Zero to Time 24 Hours [AUC (0-24)] for Axitinib (AG-013736)	416.30 nanogramhour/milliliter (nghr/mL)	Standard Deviation 450.43
Axitinib + Pemetrexed + Cisplatin (Cohort 9)	Area Under the Curve From Time Zero to Time 24 Hours [AUC (0-24)] for Axitinib (AG-013736)	420.64 nanogramhour/milliliter (nghr/mL)	Standard Deviation 200.32

Secondary

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

Arm	Measure	Value (MEAN)	Dispersion
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Area Under the Curve From Time Zero to Time 24 Hours [AUC (0-24)] for Capecitabine	20534.52 ng*hr/mL	Standard Deviation 3797.63
Axitinib + Paclitaxel + Carboplatin (Cohort 2)	Area Under the Curve From Time Zero to Time 24 Hours [AUC (0-24)] for Capecitabine	22163.88 ng*hr/mL	Standard Deviation 16881.96

Secondary

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

Arm	Measure	Value (MEAN)	Dispersion
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Area Under the Curve From Time Zero to Time 8 Hours [AUC (0-8)] for Cisplatin	2932.43 ng*hr/mL	Standard Deviation 929.69
Axitinib + Paclitaxel + Carboplatin (Cohort 2)	Area Under the Curve From Time Zero to Time 8 Hours [AUC (0-8)] for Cisplatin	2703.92 ng*hr/mL	Standard Deviation 688.68

Secondary

Maximum Observed Plasma Concentration (Cmax) for Axitinib (AG-013736)

Arm	Measure	Value (MEAN)	Dispersion
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Maximum Observed Plasma Concentration (Cmax) for Axitinib (AG-013736)	5.97 ng/mL	Standard Deviation 2.59
Axitinib + Paclitaxel + Carboplatin (Cohort 2)	Maximum Observed Plasma Concentration (Cmax) for Axitinib (AG-013736)	23.36 ng/mL	Standard Deviation 8.08
Axitinib + Paclitaxel + Carboplatin (Cohort 3)	Maximum Observed Plasma Concentration (Cmax) for Axitinib (AG-013736)	42.58 ng/mL	Standard Deviation 18.25
Axitinib + Paclitaxel (Cohort 4)	Maximum Observed Plasma Concentration (Cmax) for Axitinib (AG-013736)	44.58 ng/mL	Standard Deviation 44.78
Axitinib + Docetaxel (Cohort 5)	Maximum Observed Plasma Concentration (Cmax) for Axitinib (AG-013736)	67.96 ng/mL	Standard Deviation 39.24
Axitinib + Capecitabine (Cohort 6)	Maximum Observed Plasma Concentration (Cmax) for Axitinib (AG-013736)	37.51 ng/mL	Standard Deviation 15.31
Axitinib + Capecitabine (Cohort 7)	Maximum Observed Plasma Concentration (Cmax) for Axitinib (AG-013736)	43.97 ng/mL	Standard Deviation 28.82
Axitinib + Gemcitabine + Cisplatin (Cohort 8)	Maximum Observed Plasma Concentration (Cmax) for Axitinib (AG-013736)	40.97 ng/mL	Standard Deviation 33.06
Axitinib + Pemetrexed + Cisplatin (Cohort 9)	Maximum Observed Plasma Concentration (Cmax) for Axitinib (AG-013736)	31.53 ng/mL	Standard Deviation 22.87

Secondary

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

Arm	Measure	Value (MEAN)	Dispersion
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Maximum Observed Plasma Concentration (Cmax) for Capecitabine	10808.00 ng/mL	Standard Deviation 6173.62
Axitinib + Paclitaxel + Carboplatin (Cohort 2)	Maximum Observed Plasma Concentration (Cmax) for Capecitabine	10588.38 ng/mL	Standard Deviation 9954.76

Secondary

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

Arm	Measure	Value (MEAN)	Dispersion
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Maximum Observed Plasma Concentration (Cmax) for Carboplatin	23383.33 ng/mL	Standard Deviation 7170.75

Secondary

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

Arm	Measure	Value (MEAN)	Dispersion
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Maximum Observed Plasma Concentration (Cmax) for Cisplatin	1680.54 ng/mL	Standard Deviation 628.63
Axitinib + Paclitaxel + Carboplatin (Cohort 2)	Maximum Observed Plasma Concentration (Cmax) for Cisplatin	1176.00 ng/mL	Standard Deviation 295.29

Secondary

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

Arm	Measure	Value (MEAN)	Dispersion
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Maximum Observed Plasma Concentration (Cmax) for Docetaxel	3130.00 ng/mL	Standard Deviation 1106.23

Secondary

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

Arm	Measure	Value (MEAN)	Dispersion
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Maximum Observed Plasma Concentration (Cmax) for Gemcitabine	20635.29 ng/mL	Standard Deviation 10656.86

Secondary

Maximum Observed Plasma Concentration (Cmax) for Paclitaxel

Arm	Measure	Value (MEAN)	Dispersion
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Maximum Observed Plasma Concentration (Cmax) for Paclitaxel	3698.33 ng/mL	Standard Deviation 1198.32
Axitinib + Paclitaxel + Carboplatin (Cohort 2)	Maximum Observed Plasma Concentration (Cmax) for Paclitaxel	6105.00 ng/mL	Standard Deviation 2167.59

Secondary

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

Arm	Measure	Value (MEAN)	Dispersion
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Maximum Observed Plasma Concentration (Cmax) for Pemetrexed	83925.00 ng/mL	Standard Deviation 35820.05

Secondary

Minimum Observed Plasma Trough Concentration (Cmin) for Axitinib (AG-013736)

Population: Data was not summarized as majority of participants were having plasma concentrations below limit of assay quantification (BLQ).

Secondary

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

Population: Data was not summarized as majority of participants were having plasma concentrations below limit of assay quantification (BLQ).

Secondary

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

Population: Cmin was analyzed only for orally administered drugs.

Secondary

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

Population: Cmin was analyzed only for orally administered drugs.

Secondary

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

Population: Cmin was analyzed only for orally administered drugs.

Secondary

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

Population: Cmin was analyzed only for orally administered drugs.

Secondary

Minimum Observed Plasma Trough Concentration (Cmin) for Paclitaxel

Population: Cmin was analyzed only for orally administered drugs.

Secondary

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

Population: Cmin was analyzed only for orally administered drugs.

Secondary

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

Population: Population included all participants who received at least 1 dose of study medication and had at least 1 target lesion according to RECIST and a baseline assessment of disease.

Arm	Measure	Value (NUMBER)
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Percentage of Participants With Objective Response	100.0 Percentage of Participants
Axitinib + Paclitaxel + Carboplatin (Cohort 2)	Percentage of Participants With Objective Response	0 Percentage of Participants
Axitinib + Paclitaxel + Carboplatin (Cohort 3)	Percentage of Participants With Objective Response	35.0 Percentage of Participants
Axitinib + Paclitaxel (Cohort 4)	Percentage of Participants With Objective Response	66.7 Percentage of Participants
Axitinib + Docetaxel (Cohort 5)	Percentage of Participants With Objective Response	50.0 Percentage of Participants
Axitinib + Capecitabine (Cohort 6)	Percentage of Participants With Objective Response	11.1 Percentage of Participants
Axitinib + Capecitabine (Cohort 7)	Percentage of Participants With Objective Response	11.8 Percentage of Participants
Axitinib + Gemcitabine + Cisplatin (Cohort 8)	Percentage of Participants With Objective Response	23.8 Percentage of Participants
Axitinib + Pemetrexed + Cisplatin (Cohort 9)	Percentage of Participants With Objective Response	0 Percentage of Participants

Secondary

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

Arm	Measure	Value (MEAN)	Dispersion
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Plasma Clearance (CL) for Carboplatin	12.57 L/hr	Standard Deviation 3.99

Secondary

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

Arm	Measure	Value (MEAN)	Dispersion
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Plasma Clearance (CL) for Cisplatin	46.31 L/hr	Standard Deviation 14.57
Axitinib + Paclitaxel + Carboplatin (Cohort 2)	Plasma Clearance (CL) for Cisplatin	46.80 L/hr	Standard Deviation 14.92

Secondary

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

Arm	Measure	Value (MEAN)	Dispersion
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Plasma Clearance (CL) for Docetaxel	42.96 L/hr	Standard Deviation 6.04

Secondary

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

Arm	Measure	Value (MEAN)	Dispersion
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Plasma Clearance (CL) for Gemcitabine	224.36 L/hr	Standard Deviation 74.45

Secondary

Plasma Clearance (CL) for Paclitaxel

Arm	Measure	Value (MEAN)	Dispersion
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Plasma Clearance (CL) for Paclitaxel	30.48 L/hr	Standard Deviation 6.16
Axitinib + Paclitaxel + Carboplatin (Cohort 2)	Plasma Clearance (CL) for Paclitaxel	21.61 L/hr	Standard Deviation 9.38

Secondary

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

Arm	Measure	Value (MEAN)	Dispersion
Axitinib + Paclitaxel + Carboplatin (Cohort 1)	Plasma Clearance (CL) for Pemetrexed	7.26 L/hr	Standard Deviation 2.08

Secondary