Antineoplastic Agents

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Paclitaxel

Carboplatin

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Docetaxel

Albumin-Bound Paclitaxel

Axitinib

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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) 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 + Paclitaxel + Carboplatin (Cohort 1)

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.

Axitinib + Paclitaxel + Carboplatin (Cohort 2)

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 + Paclitaxel + Carboplatin (Cohort 3)

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 + Paclitaxel (Cohort 4)

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 + 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. 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 + Docetaxel (Cohort 5)

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 + 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 (1250 mg/m\^2) orally BID from Day 1 to Day 14 of each cycle.

Axitinib + Capecitabine (Cohort 7)

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 + 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. Pemetrexed (500 mg/m\^2) 10-minute infusion followed by cisplatin (75 mg/m\^2) infusion on Day 1 of each cycle.

Axitinib + Pemetrexed + Cisplatin (Cohort 9)

Pfizer CT.gov Call Center

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

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

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.

AUC (0-24) = Area under the plasma concentration versus time curve from time zero (pre-dose) to time 24 hours (0-24).

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.

t1/2 is the time measured for the plasma concentration to decrease by one half.

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-∞).

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.

AUC (0-8) = Area under the plasma concentration versus time curve from time zero (pre-dose) to time 8 hours (0-8).

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.

Pfizer

The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Total

Age Continuous

Sex: Female, Male

Pfizer ClinicalTrials.gov Call Center

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

Maximum Tolerated Dose (MTD) of Axitinib (AG-013736) in Combination With Chemotherapy

Axitinib (AG-013736) oral tablet of 1 mg (milligram) administered twice daily (BID) as lead in dose from Day -5, -4 or -3 to Day 2 of Cycle 1 (cycle length 21 days). AG-013736 standard dose of 5 mg oral tablet BID administered from Day 3 to Day 18 of Cycle 1 and Day 3 to Day 20 of Cycle 2 and all subsequent cycles with no interval between two cycles. Paclitaxel \[200 milligram/square meter (mg/m\^2)\] 3-hour infusion followed by carboplatin at a dose to target area under the concentration-time curve (AUC) of 6.0 milligram\*minute/milliliter (mg\*min/mL) as 30-minute infusion administered once weekly from Day 1 of Cycle 1 and all subsequent cycles.

AG-013736 3 oral tablets of 1 mg administered BID as lead in dose from Day -5, -4 or -3 to Day 2 of Cycle 1 (cycle length 21 days). AG-013736 standard dose of 5 mg oral tablet BID administered from Day 3 to Day 18 of Cycle 1 and Day 3 to Day 20 of Cycle 2 and all subsequent cycles with no interval between two cycles. Paclitaxel (200 mg/m\^2) 3-hour infusion followed by carboplatin at a dose to target AUC of 6.0 mg\*min/mL as 30-minute infusion administered once weekly from Day 1 of Cycle 1 and all subsequent cycles.

AG-013736 oral tablet of 5 mg administered BID as lead in dose from Day -5, -4 or -3 to Day 2 of Cycle 1 (cycle length 21 days). AG-013736 standard dose of 5 mg oral tablet BID administered from Day 3 to Day 18 of Cycle 1 and Day 3 to Day 20 of Cycle 2 and all subsequent cycles with no interval between two cycles. Paclitaxel (200 mg/m\^2) 3-hour infusion followed by carboplatin at a dose to target AUC of 6.0 mg\*min/mL as 30-minute infusion administered once weekly from Day 1 of Cycle 1 and all subsequent cycles.

AG-013736 oral tablet of 5 mg administered BID from Day 1 to Day 25 of Cycle 1 (cycle length 28 days) and then without interruption from Day 3 of Cycle 2 and all subsequent cycles with no interval between two cycles. Paclitaxel 90 mg/m\^2 administered as 60-minute infusion on Day 1, 8, and 15 of every cycle.

AG-013736 oral tablet of 5 mg administered BID as lead in dose from Day -5, -4 or -3 to Day 2 of Cycle 1. AG-013736 standard dose of 5 mg oral tablet BID administered from Day 3 to Day 18 of Cycle 1 (cycle length 21 days) and then without interruption from Day 3 of Cycle 2 and all subsequent cycles with no interval between two cycles. Docetaxel 100 mg/m\^2 administered as 60-minute infusion on Day 1 of every cycle.

AG-013736 oral tablet of 5 mg administered BID from Day 1 to Day 18 of Cycle 1 (cycle length 21 days) and then without interruption from Day 3 of Cycle 2 and all subsequent cycles with no interval between two cycles. Capecitabine (1000 mg/m\^2) administered orally BID from Day 1 to Day 14 of every cycle.

AG-013736 oral tablet of 5 mg administered BID from Day 1 to Day 18 of Cycle 1 (cycle length 21 days) and then without interruption from Day 3 of Cycle 2 and all subsequent cycles with no interval between two cycles. Capecitabine (1250 mg/m\^2) administered orally BID from Day 1 to Day 14 of every cycle.

AG-013736 oral tablet of 5 mg administered BID from Day -5, -4 or -3 to Day 18 of Cycle 1 (cycle length 21 days) and then without interruption from Day 3 of Cycle 2 and all subsequent cycles with no interval. Cisplatin 80 mg/m\^2 administered as infusion on Day 1 of Cycle 1 and all subsequent cycles. Gemcitabine 1250 mg/m\^2 administered as infusion on Day 1 and Day 8 of Cycle 1 and all subsequent cycles.

AG-013736 oral tablet of 5 mg administered BID from Day -5, -4 or -3 to Day 18 of Cycle 1 (cycle length 21 days) and then without interruption from Day 3 of Cycle 2 and all subsequent cycles with no interval between two cycles. Cisplatin 75 mg/m\^2 and pemetrexed 500 mg/m\^2 administered as infusion on Day 1 Cycle 1 and all subsequent cycles.

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.

Area Under the Curve From Time Zero to Time 24 Hours [AUC (0-24)] for Axitinib (AG-013736)

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

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

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

Apparent Oral Clearance (CL/F) for Axitinib (AG-013736)

Plasma Decay Half Life (t1/2) for Axitinib (AG-013736)

Combined Data from all participants in cohort 1, 2 and 3.

Axitinib + Paclitaxel + Carboplatin (Combined Cohort 1, 2, 3)

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Paclitaxel

Maximum Observed Plasma Concentration (Cmax) for Paclitaxel

Cmin was analyzed only for orally administered drugs.

Minimum Observed Plasma Trough Concentration (Cmin) for Paclitaxel

Plasma Clearance (CL) for Paclitaxel

Plasma Decay Half Life (t1/2) for Paclitaxel

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Docetaxel

Maximum Observed Plasma Concentration (Cmax) for Docetaxel

Minimum Observed Plasma Trough Concentration (Cmin) for Docetaxel

Plasma Clearance (CL) for Docetaxel

Plasma Decay Half Life (t1/2) for Docetaxel

Area Under the Curve From Time Zero to Time 24 Hours [AUC (0-24)] for Capecitabine

Maximum Observed Plasma Concentration (Cmax) for Capecitabine

Minimum Observed Plasma Trough Concentration (Cmin) for Capecitabine

Apparent Oral Clearance (CL/F) for Capecitabine

Plasma Decay Half Life (t1/2) for Capecitabine

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Gemcitabine

Maximum Observed Plasma Concentration (Cmax) for Gemcitabine

Minimum Observed Plasma Trough Concentration (Cmin) for Gemcitabine

Plasma Clearance (CL) for Gemcitabine

Plasma Decay Half Life (t1/2) for Gemcitabine

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Carboplatin

Maximum Observed Plasma Concentration (Cmax) for Carboplatin

Minimum Observed Plasma Trough Concentration (Cmin) for Carboplatin

Plasma Clearance (CL) for Carboplatin

Plasma Decay Half Life (t1/2) for Carboplatin

Area Under the Curve From Time Zero to Time 8 Hours [AUC (0-8)] for Cisplatin

Maximum Observed Plasma Concentration (Cmax) for Cisplatin

Minimum Observed Plasma Trough Concentration (Cmin) for Cisplatin

Plasma Clearance (CL) for Cisplatin

Plasma Decay Half Life (t1/2) for Cisplatin

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Pemetrexed

Maximum Observed Plasma Concentration (Cmax) for Pemetrexed

Minimum Observed Plasma Trough Concentration (Cmin) for Pemetrexed

Plasma Clearance (CL) for Pemetrexed

Plasma Decay Half Life (t1/2) for Pemetrexed

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 \[200 milligram/meter square (mg/m\^2)\] 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) 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 18 of Cycle 1 and all subsequent cycles followed by cisplatin (80 mg/m\^2) infusion on Day 1 of each cycle.

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.

Spots Global Cancer Trial Database for Investigational Agent AG-013736 In Combinations With Standard Of Care Treatments For Patient's With Advanced Solid Tumor

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