NCT00454649|CompletedPhase 1Results

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

Pfizer ClinicalTrials.gov

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1 other identifier

A4061019

Study Type

interventional

Target

102

Locations

3 countries

Sites

Timeline

RegisteredApr 2007

StartedDec 2005

CompletionApr 2011

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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

102

participants targeted

Target at P75+ for phase_1

Timeline

Completed

Started Dec 2005

Longer than P75 for phase_1

Geographic Reach

3 countries

13 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

5.3 years study duration

Study Start

First participant enrolled

December 1, 2005

Completed

1.3 years until next milestone

First Submitted

Initial submission to the registry

March 29, 2007

Completed

4 days until next milestone

First Posted

Study publicly available on registry

April 2, 2007

Completed

2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2009

Completed

1.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2011

Completed

12 months until next milestone

Results Posted

Study results publicly available

March 27, 2012

Completed

Last Updated

April 4, 2012

Status Verified

March 1, 2012

Enrollment Period

3.7 years

First QC Date

March 29, 2007

Results QC Date

February 25, 2012

Last Update Submit

March 30, 2012

Conditions

Neoplasms

Keywords

axitinibchemotherapyanti-angiogenesisVEGF inhibition

Outcome Measures

Primary Outcomes (1)

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.
Baseline to withdrawal from study or Day 21 of Cycle 1 [all cohorts except cohort 4 (Day 28 of Cycle 1)]

Secondary Outcomes (41)

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
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
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
+36 more secondary outcomes

Study Arms (1)

Axitinib [AG-013736] + chemotherapy combination

EXPERIMENTAL

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

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)

Interventions

Axitinib + Paclitaxel + Carboplatin (Cohort 1)DRUG

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.