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Completed

NCT Number: NCT00454649

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

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

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Key information

Conditions

Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Pfizer Investigational Site, Warsaw, Poland

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

Axitinib + Paclitaxel + Carboplatin (Cohort 2)

Drug

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 3)

Drug

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 (Cohort 4)

Drug

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 + Docetaxel + Carboplatin (Cohort 4a)

Drug

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 (Cohort 5)

Drug

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 + Capecitabine (Cohort 6)

Drug

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 7)

Drug

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 + Gemcitabine + Cisplatin (Cohort 8)

Drug

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 + Pemetrexed + Cisplatin (Cohort 9)

Drug

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.

Primary outcomes

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

    Time frame: 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 outcomes

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

    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

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

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

    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

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

    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

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

    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

    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.

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

    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

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

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

    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

    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-∞).

  7. Maximum Observed Plasma Concentration (Cmax) for Paclitaxel

    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

  8. Minimum Observed Plasma Trough Concentration (Cmin) for Paclitaxel

    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

  9. Plasma Clearance (CL) for Paclitaxel

    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

    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.

  10. Plasma Decay Half Life (t1/2) for Paclitaxel

    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

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

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

    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-∞).

  12. 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

  13. 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

  14. 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

    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.

  15. Plasma Decay Half Life (t1/2) 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

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

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

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

  17. 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

  18. 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

  19. 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

    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.

  20. Plasma Decay Half Life (t1/2) 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

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

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

    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-∞).

  22. 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

  23. 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

  24. 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

    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.

  25. Plasma Decay Half Life (t1/2) 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

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

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

    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-∞).

  27. 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

  28. 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

  29. Plasma Clearance (CL) 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

    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.

  30. Plasma Decay Half Life (t1/2) 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

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

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

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

  32. 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

  33. 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

  34. 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

    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.

  35. Plasma Decay Half Life (t1/2) 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

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

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

    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-∞).

  37. 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

  38. 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

  39. 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

    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.

  40. Plasma Decay Half Life (t1/2) 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

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

  41. Percentage of Participants With Objective Response

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study 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

Important dates

Study start
2005
Primary completion
2009
Study completion
2011
First posted
Apr 2, 2007
Registry last updated
Apr 4, 2012

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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