Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Stomach Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

Antineoplastic Agents

All Drugs and Chemicals

Capecitabine

Axitinib

Cisplatin

Antimetabolites

Protein Kinase Inhibitors

Enzyme Inhibitors

Twice daily oral dose of axitinib continuously depending upon side effects observed. Starting dose is 5mg twice daily. Each 21 day cycle is repeated until progression of disease or unacceptable toxicity is observed.

axitinib

Given orally twice daily for 14 days followed by 7 days of drug free period. Starting dose is 1000mg/m\^2 twice daily. Each 21 day cycle is repeated until progression of disease or unacceptable toxicity is observed.

capecitabine

Given through a vein on Day 1 of every 21 days. Each 21 day cycle is repeated until progression of disease or unacceptable toxicity is observed. The starting dose is 80 mg/m\^2 on day 1.

cisplatin

Pfizer CT.gov Call Center

The purpose of this study is to determine the safe and tolerable dose of axitinib given together with cisplatin and capecitabine in patients with advanced gastric cancer who have not received prior chemotherapy for their advanced cancer.

Study Of Axitinib In Combination With Cisplatin And Capecitabine In Patients With Advanced Gastric Cancer

A Phase 1 Study Of Axitinib In Combination With Cisplatin And Capecitabine In Patients With Advanced Gastric Cancer

MTD = highest dose at which no more than 30 percent (%) of 12 participants experience DLT during Cycle 1. DLT = GR2 proteinuria; GR3 NHT (excluding alopecia and those that can be controlled with appropriate treatment)for \>=7 days, GR3 thrombocytopenia with active bleeding; GR \>=3 febrile NP/NP infection; GR 3 or 4 nausea, vomiting or diarrhea despite anti-emetics, anti-diarrheals; GR4 NHT, thrombocytopenia, NP for \>=7 days; \>= 1/2 teaspoon per day hemoptysis; any treatment-related toxicity with \>3 consecutive days of capecitabine or 5 consecutive days of axitinib missed doses per cycle; delayed toxicity recovery \>14 days.

DLT = Grade (GR) 2 proteinuria; GR3 nonhematological toxicity (NHT) (excluding alopecia and those that can be controlled with appropriate treatment) for greater than or equal to (\>=)7 days, GR3 thrombocytopenia with active bleeding; GR \>=3 febrile neutropenia (NP) or NP infection; GR 3 or 4 nausea, vomiting or diarrhea despite anti-emetics, anti-diarrheals; GR4 NHT, thrombocytopenia, NP for \>=7 days; \>= 1/2 teaspoon per day hemoptysis; any treatment related toxicity with \>3 consecutive days of capecitabine or 5 consecutive days of axitinib missed doses per cycle; delayed toxicity recovery \>14 days.

Cmax for axitinib in absence of chemotherapy (axitinib alone) was evaluated on Cycle 1 Day -1 and in combination with chemotherapy on Cycle 1 Day 1. Cmax for cisplatin (assessed by estimating total platinum in plasma ultrafiltrate), capecitabine and capecitabine's metabolites (5-fluorouracil \[5-FU\], 5-deoxy-5-fluorouridine \[5-DFUR\] and 5-deoxy-5-fluorocytidine \[5-DFC\]) in presence of steady-state axitinib were evaluated on Cycle 1 Day 1 and in absence of axitinib (cisplatin/capecitabine alone) on Cycle 2 Day 1. Results for axitinib were normalized to axitinib 5 mg dose, results for capecitabine and its metabolites (5-FU, 5-DFUR and 5-DFC) were normalized to Cycle 1 Day 1 capecitabine dose and results for cisplatin were normalized to Cycle 1 Day 1 cisplatin dose.

Tmax for axitinib in absence of chemotherapy (axitinib alone) was evaluated on Cycle 1 Day -1 and in combination with chemotherapy on Cycle 1 Day 1. Tmax for cisplatin (assessed by estimating total platinum in plasma ultrafiltrate), capecitabine and capecitabine's metabolites (5-FU, 5-DFUR and 5-DFC) in presence of steady-state axitinib were evaluated on Cycle 1 Day 1 and in absence of axitinib (cisplatin/capecitabine alone) on Cycle 2 Day 1.

Area under the plasma concentration time-curve from zero to the last measurable concentration (AUClast). AUClast for cisplatin (assessed by estimating total platinum in plasma ultrafiltrate), capecitabine and capecitabine's metabolites (5-FU, 5-DFUR, 5-DFC) in presence of steady-state axitinib were evaluated on Cycle 1 Day 1 and in absence of axitinib (cisplatin/capecitabine alone) on Cycle 2 Day 1. Results for capecitabine and its metabolites (5-FU, 5-DFUR and 5-DFC) were normalized to Cycle 1 Day 1 capecitabine dose and results for cisplatin were normalized to Cycle 1 Day 1 cisplatin dose.

AUC (0-24) = Area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours. AUC (0-24) for axitinib in absence of chemotherapy (axitinib alone) was evaluated on Cycle 1 Day -1 and in combination with chemotherapy on Cycle 1 Day 1. Results for axitinib were normalized to axitinib 5 mg dose.

AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) extrapolated to infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). AUC (0 - ∞) for axitinib in absence of chemotherapy (axitinib alone) was evaluated on Cycle 1 Day -1 and in combination with chemotherapy on Cycle 1 Day 1. AUC (0 - ∞) for cisplatin (assessed by estimating total platinum in plasma ultrafiltrate), capecitabine and capecitabine's metabolites (5-FU, 5-DFUR and 5-DFC) in presence of steady-state axitinib were evaluated on Cycle 1 Day 1 and in absence of axitinib (cisplatin/capecitabine alone) on Cycle 2 Day 1. Results for axitinib were normalized to axitinib 5 mg dose, results for capecitabine and its metabolites (5-FU, 5-DFUR and 5-DFC) were normalized to Cycle 1 Day 1 capecitabine dose and results for cisplatin were normalized to Cycle 1 Day 1 cisplatin dose.

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Plasma decay half life for axitinib in absence of chemotherapy (axitinib alone) was evaluated on Cycle 1 Day -1 and in combination with chemotherapy on Cycle 1 Day 1. Plasma decay half life for cisplatin (assessed by estimating total platinum in plasma ultrafiltrate), capecitabine and capecitabine's metabolites (5-FU, 5-DFUR and 5-DFC) in presence of steady-state axitinib were evaluated on Cycle 1 Day 1 and in absence of axitinib (cisplatin/capecitabine alone) on Cycle 2 Day 1.

Clearance (CL) of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed (F). Clearance is defined as the volume of blood from which drug can be completely removed per unit of time. CL/F for axitinib in absence of chemotherapy (axitinib alone) was evaluated on Cycle 1 Day -1 and in combination with chemotherapy on Cycle 1 Day 1. CL/F for capecitabine in presence of steady-state axitinib was evaluated on Cycle 1 Day 1 and in absence of axitinib (capecitabine alone) on Cycle 2 Day 1.

Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. It is defined as the volume of blood from which drug can be completely removed per unit of time. Clearance for cisplatin (assessed by estimating total platinum in plasma ultrafiltrate) in presence of steady-state axitinib was evaluated on Cycle 1 Day 1 and in absence of axitinib (cisplatin alone) on Cycle 2 Day 1.

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vz/F is influenced by the fraction absorbed. Vz/F for axitinib in absence of chemotherapy (axitinib alone) was evaluated on Cycle 1 Day -1 and in combination with chemotherapy on Cycle 1 Day 1. Vz/F for capecitabine in presence of steady-state axitinib was evaluated on Cycle 1 Day 1 and in absence of axitinib (capecitabine alone) on Cycle 2 Day 1.

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Clearance for cisplatin (assessed by estimating total platinum in plasma ultrafiltrate) in presence of steady-state axitinib was evaluated on Cycle 1 Day 1 and in absence of axitinib (cisplatin alone) on Cycle 2 Day 1.

Genetic variants of uridine diphosphate (UDP)- glucuronosyl transferase 1A1 (UGT1A1) gene which were assessed for genotyping included UGT1A1\*60, UGT1A1-3156, UGT1A1 Promoter thymine adenine (TA) repeat (UGT1A1\*28, UGT1A1\*36, UGT1A1\*37), UGT1A1\*6 and UGT1A1\*27.

Number 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). Confirmed response are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR are those with disappearance of all target lesions. PR are those with at least 30 percent (%) decrease in sum of the longest dimensions of target lesions taking the baseline sum of the longest dimensions as a reference.

Time in months from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.4. DR was calculated for the subgroup of participants with a confirmed objective tumor response. CR = disappearance of all target lesions. PR = at least 30% decrease in sum of the longest dimensions of target lesions taking the baseline sum of the longest dimensions as a reference.

Time in months from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.4. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]), or from adverse event (AE) data (where the outcome was "Death"). PD was a\>=20% increase in sum of the longest dimensions of target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of 1 or more new lesions.

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.

Axitinib (AG-013736) 5 milligram (mg) tablet orally twice daily in cycles of 21 days, capecitabine 1000 mg per square meter (mg/m\^2) tablet orally twice daily from Day 1 to 14 of each cycle and cisplatin 80 mg/m\^2 infusion over 2 hours (hrs) on Day 1 of each cycle, in cycles of 21 days. Participants enrolled in pharmacokinetic (PK) expansion cohort at maximum tolerated dose (MTD) received axitinib (AG-013736) 5 mg orally twice daily starting from Day -3 to Day 18 in Cycle 1 (21 days cycle) and thereafter axitinib (AG-013736) 5 mg orally twice daily starting from Cycle 2 Day 2, capecitabine 1000 mg/m\^2 tablet orally twice daily from Day 1 to 14 and cisplatin 80 mg/m\^2 infusion over 2 hrs on Day 1 of each cycle, in cycles of 21 days.

Axitinib + Capecitabine + Cisplatin

Age Continuous

Sex: Female, Male

AUC (0-24) was evaluated and reported for axitinib instead of AUClast as AUC0-24 was a more appropriate measure of steady-state exposure for this drug.

Pfizer ClinicalTrials.gov Call Center

Axitinib (AG-013736) 5 mg tablet orally twice daily in cycles of 21 days, capecitabine 1000 mg/m\^2 tablet orally twice daily from Day 1 to 14 of each cycle and cisplatin 80 mg/m\^2 infusion over 2 hrs on Day 1 of each cycle, in cycles of 21 days.

Axitinib + Capecitabine + Cisplatin (MTD Determination)

DLT analysis set: participants who received first cycle of study treatment and did not temporarily or permanently discontinue or miss more than 5 consecutive days of axitinib (AG-13736) or more than 3 consecutive days of capecitabine for reasons other than DLTs within first cycle.

Number of Participants With Cycle 1 Dose-limiting Toxicities (DLTs)

Maximum Tolerated Dose (MTD) of Axitinib (AG-013736) in Combination With Cisplatin and Capecitabine

Axitinib alone (n = 10)

Axitinib in combination with chemotherapy (n = 10)

Capecitabine alone (n = 8)

Capecitabine in presence of axitinib (n = 8)

5-FU alone (n = 8)

5-FU in presence of axitinib (n = 8)

5-DFUR alone (n = 8)

5-DFUR in presence of axitinib (n = 8)

5-DFC alone (n = 8)

5-DFC in presence of axitinib (n = 8)

Cisplatin alone (n = 8)

Cisplatin in presence of axitinib (n = 8)

Participants enrolled in PK expansion cohort at MTD received axitinib (AG-013736) 5 mg orally twice daily starting from Day -3 to Day 18 in Cycle 1 (21 days cycle) and thereafter axitinib (AG-013736) 5 mg orally twice daily starting from Cycle 2 Day 2, capecitabine 1000 mg/m\^2 tablet orally twice daily from Day 1 to 14 and cisplatin 80 mg/m\^2 infusion over 2 hrs on Day 1 of each cycle, in cycles of 21 days.

Axitinib + Capecitabine + Cisplatin (PK Expansion Cohort)

Pharmacokinetic parameter analysis set included all treated participants who had at least 1 estimated pharmacokinetic parameter of primary interest. Here, 'n' signifies those participants who were evaluable for specified study drug's PK parameter alone or in combination.

Maximum Observed Plasma Concentration (Cmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin

Time to Reach Maximum Observed Plasma Concentration (Tmax) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin

Capecitabine alone

Capecitabine in presence of axitinib

5-FU alone

5-FU in presence of axitinib

5-DFUR alone

5-DFUR in presence of axitinib

5-DFC alone

5-DFC in presence of axitinib

Cisplatin alone

Cisplatin in presence of axitinib

Pharmacokinetic parameter analysis set included all treated participants who had at least 1 estimated pharmacokinetic parameter of primary interest. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Capecitabine, Capecitabine's Metabolites and Cisplatin

Axitinib alone

Axitinib in combination with chemotherapy

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

Axitinib alone (n = 9)

Axitinib in combination with chemotherapy (n = 9)

Capecitabine alone (n = 6)

Capecitabine in presence of axitinib (n = 6)

5-FU alone (n = 3)

5-FU in presence of axitinib (n = 3)

5-DFUR alone (n = 4)

5-DFUR in presence of axitinib (n = 4)

5-DFC alone (n = 5)

5-DFC in presence of axitinib (n = 5)

Cisplatin alone (n = 7)

Cisplatin in presence of axitinib (n = 7)

Pharmacokinetic parameter analysis set. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. Here, 'n' signifies those participants who were evaluable for specified study drug's PK parameter alone or in combination.

Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUC (0 - ∞)] for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin

Plasma Decay Half-Life (t1/2) for Axitinib, Capecitabine, Capecitabine's Metabolites and Cisplatin

Pharmacokinetic parameter analysis set. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. 'n' = participants evaluable for specified study drug's PK parameter alone or in combination. Results are not reported for capecitabine metabolites because CL/F could not be accurately estimated.

Apparent Oral Clearance (CL/F) for Axitinib, Capecitabine and Capecitabine's Metabolites

Clearance (CL) for Cisplatin

Pharmacokinetic parameter analysis set. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. 'n' = participants evaluable for specified study drug's PK parameter alone or in combination. Results are not reported for capecitabine metabolites because Vz/F could not be accurately estimated.

Apparent Volume of Distribution (Vz/F) for Axitinib, Capecitabine and Capecitabine's Metabolites

Volume of Distribution (Vz) for Cisplatin

Axitinib (AG-013736) 5 milligram (mg) tablet orally twice daily in cycles of 21 days, capecitabine 1000 mg per square meter (mg/m\^2) tablet orally twice daily from Day 1 to 14 of each cycle and cisplatin 80 mg/m\^2 infusion over 2 hours (hrs) on Day 1 of each cycle, in cycles of 21 days. Participants enrolled in Pharmacokinetic (PK) expansion cohort at MTD received axitinib (AG-013736) 5 mg orally twice daily starting from Day -3 to Day 18 in Cycle 1 (21 days cycle) and thereafter axitinib (AG-013736) 5 mg orally twice daily starting from Cycle 2 Day 2, capecitabine 1000 mg/m\^2 tablet orally twice daily from Day 1 to 14 and cisplatin 80 mg/m\^2 infusion over 2 hrs on Day 1 of each cycle, in cycles of 21 days.

Results are not reported because data was reported in individual participant listing but not statistically summarized for the analysis.

Drug Metabolizing Enzyme Genotyping

Efficacy analysis set included all enrolled participants who received at least 1 dose of study medication, had measurable disease at baseline (according to RECIST criteria version 1.0), and had at least 1 tumor assessment during study.

Percentage of Participants With Objective Response (OR)

Analysis set included a subset of efficacy analysis set who had confirmed objective tumor response.

Spots Global Cancer Trial Database for Study Of Axitinib In Combination With Cisplatin And Capecitabine In Patients With Advanced Gastric Cancer

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