Study Of Sunitinib In Combination With Cisplatin/Capecitabine Or Oxaliplatin/Capecitabine In Patients With Advanced Gastric Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00555620
First received: November 6, 2007
Last updated: January 7, 2013
Last verified: January 2013
  Purpose

The purpose of the study is to determine the safe and tolerable doses of sunitinib given together with either cisplatin and capecitabine or oxaliplatin and capecitabine in patients who have advanced gastric cancer who have not received prior chemotherapy for their advanced cancer


Condition Intervention Phase
Stomach Neoplasms
Drug: capecitabine
Drug: oxaliplatin
Drug: sunitinib malate
Drug: cisplatin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study Of Sunitinib Malate In Combination With Cisplatin/Capecitabine Or Oxaliplatin/Capecitabine In Patients With Advanced Gastric Cancer

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of Participants With First-cycle Dose Limiting Toxicities (DLTs) [ Time Frame: Baseline up to Day 21 ] [ Designated as safety issue: Yes ]
    Any DLT event in Cycle 1: Grade (GR) 3/4 nausea, vomiting, or diarrhea despite anti-emetics, anti-diarrheals; GR 3 nonhematological toxicity for greater than or equal to (≥)7 days (except alopecia, skin or hair discoloration, hyperamylasemia, or hyperlipasemia without other clinical evidence of pancreatitis and asymptomatic hyperuricemia); GR 4 nonhematological toxicity; GR 4 neutropenia ≥7 days or thrombocytopenia; GR ≥3 febrile neutropenia or neutropenic infection; GR 3 thrombocytopenia ≥7 days; any treatment-related toxicity having >3 consecutive CAP or SU missed doses per cycle; delayed toxicity recovery >14 days.


Secondary Outcome Measures:
  • Maximum Observed Plasma Concentration (Cmax) of SU, SU012662 (Metabolite of SU), and Total Drug (SU + SU012662) [ Time Frame: Day 14 of Cycle 1 (predose and 2, 4, 6, 8, 10, and 24 hours postdose) ] [ Designated as safety issue: No ]
  • Cmax of CAP [ Time Frame: Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) ] [ Designated as safety issue: No ]
  • Cmax of 5'-Deoxy-5-fluorocytidine (Metabolite of CAP, 5'DFCR) [ Time Frame: Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) ] [ Designated as safety issue: No ]
  • Cmax of 5'-Deoxy-5-fluorouridine (Metabolite of CAP, 5'DFUR) [ Time Frame: Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) ] [ Designated as safety issue: No ]
  • Cmax of 5-fluorouracil (Metabolite of CAP, 5-FU) [ Time Frame: Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) ] [ Designated as safety issue: No ]
  • Minimum Observed Plasma Trough Concentration (Cmin) of SU, SU012662, and Total Drug (SU + SU012662) [ Time Frame: Day 14 of Cycle 1 (predose and 2, 4, 6, 8, 10, and 24 hours postdose) ] [ Designated as safety issue: No ]
  • Cmin of CAP [ Time Frame: Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) ] [ Designated as safety issue: No ]
  • Cmin of 5'DFCR [ Time Frame: Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) ] [ Designated as safety issue: No ]
  • Cmin of 5'DFUR [ Time Frame: Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) ] [ Designated as safety issue: No ]
  • Cmin of 5-FU [ Time Frame: Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) for SU, SU012662, and Total Drug (SU + SU012662) [ Time Frame: Day 14 of Cycle 1 (predose and 2, 4, 6, 8, 10, and 24 hours postdose) ] [ Designated as safety issue: No ]
  • Tmax for CAP [ Time Frame: Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) ] [ Designated as safety issue: No ]
  • Tmax for 5'DFCR [ Time Frame: Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) ] [ Designated as safety issue: No ]
  • Tmax for 5'DFUR [ Time Frame: Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) ] [ Designated as safety issue: No ]
  • Tmax for 5-FU [ Time Frame: Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) ] [ Designated as safety issue: No ]
  • Terminal Elimination Half-Life (t1/2) for SU, SU012662, and Total Drug (SU + SU012662) [ Time Frame: Day 14 of Cycle 1 (predose and 2, 4, 6, 8, 10, and 24 hours postdose) ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  • t1/2 for CAP [ Time Frame: Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  • t1/2 for 5'DFCR [ Time Frame: Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  • t1/2 for 5'DFUR [ Time Frame: Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  • t1/2 for 5-FU [ Time Frame: Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  • Area Under the Curve From Time 0 to 24 Hours Postdose (AUC [0-24]) for SU, SU012662, and Total Drug (SU + SU012662) [ Time Frame: Day 14 of Cycle 1 (predose and 2, 4, 6, 8, 10, and 24 hours postdose) ] [ Designated as safety issue: No ]
    Area under the plasma concentration-time curve from time 0 to 24 hours postdose (0-24), also considered the AUC between doses at steady state.

  • Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]: CAP, 5'DFCR, 5'DFUR, and 5-FU [ Time Frame: Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) ] [ Designated as safety issue: No ]
    AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (predose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).

  • Area Under the Curve From Time Zero to 12 Hours [AUC (12)] for CAP, 5'DFCR, 5'DFUR, and 5-FU [ Time Frame: Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) ] [ Designated as safety issue: No ]
    AUC (12) = Area under the plasma concentration versus time curve from time zero (predose) to the extrapolated time 12 hours postdose. It is obtained from AUC (0 - last) plus AUC (last - 12)

  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for CAP [ Time Frame: Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) and Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours) ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

  • AUClast for 5'DFCR [ Time Frame: Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) and Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours) ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

  • AUClast for 5'DFUR [ Time Frame: Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) and Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours) ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

  • AUClast for 5-FU [ Time Frame: Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) and Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours) ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

  • Percentage of Participants With Objective Response [ Time Frame: Baseline, Day 21 of every even-numbered cycle up to 15 months ] [ Designated as safety issue: No ]
    Percentage of participants with an objective response-based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR defined as the disappearance of all target lesions. PR defined as ≥30 percent (%) decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.

  • Duration of Response (DR) [ Time Frame: Baseline up to Month 15 ] [ Designated as safety issue: No ]
    DR defined as time from start of first documented objective tumor response (CR or PR) to first documented objective tumor progression or death due to any cause, whichever occurs first.

  • Progression-Free Survival (PFS) [ Time Frame: Baseline up to Month 15 ] [ Designated as safety issue: No ]
    PFS defined as time from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.


Enrollment: 76
Study Start Date: May 2008
Study Completion Date: December 2011
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: capecitabine
Capecitabine is given orally at 1000mg/m^2 twice a day for 14 days followed by 7 days of drug free period.
Drug: oxaliplatin
Oxaliplatin is given 110mg/m^2 through a vein on day 1 every 21 days. Each 21 day cycle is repeated until progression of disease or unacceptable toxicity is observed.
Drug: sunitinib malate
sunitinib is given orally 25mg/day for 14 days followed by 7 days of drug free period.
Other Name: Sutent
Experimental: B Drug: capecitabine
Capecitabine is given orally at 1000mg/m^2 twice a day for 14 days followed by 7 days of drug free period.
Drug: cisplatin
Cisplatin is given 80mg/m^2 through a vein on day 1 every 21 days. Each 21 day cycle is repeated until progression of disease or unacceptable toxicity is observed.
Drug: sunitinib malate
sunitinib is given orally 25mg/day for 14 days followed by 7 days of drug free period.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • confirmed diagnosis of stomach cancer
  • advanced stomach cancer of stage IV
  • adequate blood chemistry, blood counts and kidney function
  • willing to participate to study requirements and sign an informed consent document

Exclusion Criteria:

  • prior chemotherapy for the stomach cancer in its advanced stage
  • excessive toxicities related to prior therapies
  • pregnant or breastfeeding patients
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00555620

Locations
Korea, Republic of
Pfizer Investigational Site
Seongnam-si, Gyeonggi-do, Korea, Republic of, 463-707
Pfizer Investigational Site
Goyang, Gyeonggi, Korea, Republic of, 410-769
Pfizer Investigational Site
Seoul, Korea, Republic of, 110-744
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00555620     History of Changes
Other Study ID Numbers: A6181126
Study First Received: November 6, 2007
Results First Received: August 4, 2011
Last Updated: January 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Stomach Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Neoplasms
Neoplasms by Site
Stomach Diseases
Capecitabine
Cisplatin
Fluorouracil
Oxaliplatin
Sunitinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014