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

Phase 1

Completed

• Conditions: Neoplasms
• Interventions: 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)

• Registration Number: NCT00454649
• Lead Sponsor: Pfizer

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2005-12
• Study First Submitted: 2007-03-29
• Study First Submitted QC: 2007-03-30
• Study First Posted: 2007-04-02
• Primary Completion: 2009-08
• Study Completion: 2011-04
• Results First Submitted: 2012-02-25
• Results First Submitted QC: 2012-02-25
• Status Verified: 2012-03
• Results First Posted: 2012-03-27
• Last Update Submitted: 2012-03-30
• Last Update Posted: 2012-04-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 102

Inclusion Criteria

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

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Exclusion Criteria

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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Axitinib [AG-013736] + chemotherapy combination	Axitinib + Paclitaxel + Carboplatin (Cohort 1)	The following separate groups were included: axitinib 1. plus carboplatin/paclitaxel in three different schedules 2. plus paclitaxel 3. plus docetaxel/carboplatin 4. plus docetaxel 5. plus capecitabine 6. plus gemcitabine/cisplatin 7. plus pemetrexed/cisplatin
Axitinib [AG-013736] + chemotherapy combination	Axitinib + Capecitabine (Cohort 6)	The following separate groups were included: axitinib 1. plus carboplatin/paclitaxel in three different schedules 2. plus paclitaxel 3. plus docetaxel/carboplatin 4. plus docetaxel 5. plus capecitabine 6. plus gemcitabine/cisplatin 7. plus pemetrexed/cisplatin
Axitinib [AG-013736] + chemotherapy combination	Axitinib + Capecitabine (Cohort 7)	The following separate groups were included: axitinib 1. plus carboplatin/paclitaxel in three different schedules 2. plus paclitaxel 3. plus docetaxel/carboplatin 4. plus docetaxel 5. plus capecitabine 6. plus gemcitabine/cisplatin 7. plus pemetrexed/cisplatin
Axitinib [AG-013736] + chemotherapy combination	Axitinib + Paclitaxel + Carboplatin (Cohort 2)	The following separate groups were included: axitinib 1. plus carboplatin/paclitaxel in three different schedules 2. plus paclitaxel 3. plus docetaxel/carboplatin 4. plus docetaxel 5. plus capecitabine 6. plus gemcitabine/cisplatin 7. plus pemetrexed/cisplatin
Axitinib [AG-013736] + chemotherapy combination	Axitinib + Paclitaxel (Cohort 4)	The following separate groups were included: axitinib 1. plus carboplatin/paclitaxel in three different schedules 2. plus paclitaxel 3. plus docetaxel/carboplatin 4. plus docetaxel 5. plus capecitabine 6. plus gemcitabine/cisplatin 7. plus pemetrexed/cisplatin
Axitinib [AG-013736] + chemotherapy combination	Axitinib + Paclitaxel + Carboplatin (Cohort 3)	The following separate groups were included: axitinib 1. plus carboplatin/paclitaxel in three different schedules 2. plus paclitaxel 3. plus docetaxel/carboplatin 4. plus docetaxel 5. plus capecitabine 6. plus gemcitabine/cisplatin 7. plus pemetrexed/cisplatin
Axitinib [AG-013736] + chemotherapy combination	Axitinib + Docetaxel + Carboplatin (Cohort 4a)	The following separate groups were included: axitinib 1. plus carboplatin/paclitaxel in three different schedules 2. plus paclitaxel 3. plus docetaxel/carboplatin 4. plus docetaxel 5. plus capecitabine 6. plus gemcitabine/cisplatin 7. plus pemetrexed/cisplatin
Axitinib [AG-013736] + chemotherapy combination	Axitinib + Docetaxel (Cohort 5)	The following separate groups were included: axitinib 1. plus carboplatin/paclitaxel in three different schedules 2. plus paclitaxel 3. plus docetaxel/carboplatin 4. plus docetaxel 5. plus capecitabine 6. plus gemcitabine/cisplatin 7. plus pemetrexed/cisplatin
Axitinib [AG-013736] + chemotherapy combination	Axitinib + Gemcitabine + Cisplatin (Cohort 8)	The following separate groups were included: axitinib 1. plus carboplatin/paclitaxel in three different schedules 2. plus paclitaxel 3. plus docetaxel/carboplatin 4. plus docetaxel 5. plus capecitabine 6. plus gemcitabine/cisplatin 7. plus pemetrexed/cisplatin
Axitinib [AG-013736] + chemotherapy combination	Axitinib + Pemetrexed + Cisplatin (Cohort 9)	The following separate groups were included: axitinib 1. plus carboplatin/paclitaxel in three different schedules 2. plus paclitaxel 3. plus docetaxel/carboplatin 4. plus docetaxel 5. plus capecitabine 6. plus gemcitabine/cisplatin 7. plus pemetrexed/cisplatin

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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).
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-∞).
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
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.

Trial Locations

Locations (1)

Pfizer Investigational Site; 🇪🇸 Madrid, Spain