Clinical trial NCT00454649: Investigational Agent AG-013736 In Combinations With Standard Of Care Treatments For Patient's With Advanced Solid Tumor
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Keywords: axitinib
chemotherapy
anti-angiogenesis
VEGF inhibition
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2007-04-02
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of Axitinib (AG-013736) in Combination With Chemotherapy
timeFrame: Baseline to withdrawal from study or Day 21 of Cycle 1 [all cohorts except cohort 4 (Day 28 of Cycle 1)]
Secondary outcomes:
measure: Area Under the Curve From Time Zero to Time 24 Hours [AUC (0-24)] for Axitinib (AG-013736)
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) for Axitinib (AG-013736)
timeFrame: 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
measure: Minimum Observed Plasma Trough Concentration (Cmin) for Axitinib (AG-013736)
timeFrame: 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
measure: Apparent Oral Clearance (CL/F) for Axitinib (AG-013736)
timeFrame: 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
measure: Plasma Decay Half Life (t1/2) for Axitinib (AG-013736)
timeFrame: 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
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Paclitaxel
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) for Paclitaxel
timeFrame: 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
measure: Minimum Observed Plasma Trough Concentration (Cmin) for Paclitaxel
timeFrame: 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
measure: Plasma Clearance (CL) for Paclitaxel
timeFrame: 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
measure: Plasma Decay Half Life (t1/2) for Paclitaxel
timeFrame: 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
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Docetaxel
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) for Docetaxel
timeFrame: 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
measure: Minimum Observed Plasma Trough Concentration (Cmin) for Docetaxel
timeFrame: 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
measure: Plasma Clearance (CL) for Docetaxel
timeFrame: 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
measure: Plasma Decay Half Life (t1/2) for Docetaxel
timeFrame: 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
measure: Area Under the Curve From Time Zero to Time 24 Hours [AUC (0-24)] for Capecitabine
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) for Capecitabine
timeFrame: 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
measure: Minimum Observed Plasma Trough Concentration (Cmin) for Capecitabine
timeFrame: 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
measure: Apparent Oral Clearance (CL/F) for Capecitabine
timeFrame: 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
measure: Plasma Decay Half Life (t1/2) for Capecitabine
timeFrame: 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
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Gemcitabine
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) for Gemcitabine
timeFrame: 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
measure: Minimum Observed Plasma Trough Concentration (Cmin) for Gemcitabine
timeFrame: 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
measure: Plasma Clearance (CL) for Gemcitabine
timeFrame: 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
measure: Plasma Decay Half Life (t1/2) for Gemcitabine
timeFrame: 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
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Carboplatin
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) for Carboplatin
timeFrame: 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
measure: Minimum Observed Plasma Trough Concentration (Cmin) for Carboplatin
timeFrame: 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
measure: Plasma Clearance (CL) for Carboplatin
timeFrame: 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
measure: Plasma Decay Half Life (t1/2) for Carboplatin
timeFrame: 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
measure: Area Under the Curve From Time Zero to Time 8 Hours [AUC (0-8)] for Cisplatin
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) for Cisplatin
timeFrame: 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
measure: Minimum Observed Plasma Trough Concentration (Cmin) for Cisplatin
timeFrame: 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
measure: Plasma Clearance (CL) for Cisplatin
timeFrame: 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
measure: Plasma Decay Half Life (t1/2) for Cisplatin
timeFrame: 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
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Pemetrexed
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) for Pemetrexed
timeFrame: 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
measure: Minimum Observed Plasma Trough Concentration (Cmin) for Pemetrexed
timeFrame: 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
measure: Plasma Clearance (CL) for Pemetrexed
timeFrame: 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
measure: Plasma Decay Half Life (t1/2) for Pemetrexed
timeFrame: 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
measure: Percentage of Participants With Objective Response
timeFrame: Baseline and thereafter every 2 cycles up to disease progression or discontinuation from study or up to 155 weeks
Other outcomes:
Locations:
city: Augusta
country: United States
facility: Pfizer Investigational Site
state: Georgia
city: Augusta
country: United States
facility: Pfizer Investigational Site
state: Georgia
city: Harvey
country: United States
facility: Pfizer Investigational Site
state: Illinois
city: Harvey
country: United States
facility: Pfizer Investigational Site
state: Illinois
city: Tinley Park
country: United States
facility: Pfizer Investigational Site
state: Illinois
city: Hobart
country: United States
facility: Pfizer Investigational Site
state: Indiana
city: Munster
country: United States
facility: Pfizer Investigational Site
state: Indiana
city: Philadelphia
country: United States
facility: Pfizer Investigational Site
state: Pennsylvania
city: Houston
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Kennewick
country: United States
facility: Pfizer Investigational Site
state: Washington
city: Warszawa
country: Poland
facility: Pfizer Investigational Site
city: Barcelona
country: Spain
facility: Pfizer Investigational Site
city: Madrid
country: Spain
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: