Clinical Trial: Study Of Gemcitabine Plus AG-013736 Versus Gemcitabine For Advanced Pancreatic Cancer.

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomized, Double-Blind Phase 3 Study Of Gemcitabine Plus AG-013736 Versus Gemcitabine Plus Placebo For The First-Line Treatment Of Patients With Locally Advanced, Unresectable Or Metastatic Pancre

Brief Summary: The purpose of this study is to determine whether investigational study drug, AG-013736, and gemcitabine are effective in the first-line treatment of advanced pancreatic cancer.

Detailed Summary: This study was prematurely discontinued for futility on 23 January 2009, based on a planned interim analysis by an independent Data Safety Monitoring Board (DSMB) that found no evidence of improvement in the primary endpoint (survival) in patients treated with axitinib and gemcitabine compared to gemcitabine alone. Enrollment on this study has been discontinued.
Sponsor: Pfizer

Current Primary Outcome: Overall Survival (OS) [ Time Frame: Baseline until death or at least 1 year after the randomization of last participant ]

Time in weeks from randomization to date of death due to any cause. OS was calculated as (the death date minus the date of randomization plus 1) divided by 7. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).


Original Primary Outcome: Overall survival is the primary endpoint. A total of 596 patients and 460 events are required for a log rank test to have an overall 1 sided significance level of 0.025 and power of 0.90.

Current Secondary Outcome:

  • Progression Free Survival (PFS) [ Time Frame: Baseline until disease progression or at least 1 year after the randomization of last participant ]
    Time in weeks from randomization to the first documentation of objective tumor progression or death due to any cause. PFS was calculated as = (first event date minus randomization date plus 1) divided by 7. 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").
  • Percentage of Participants With Objective Response (OR) [ Time Frame: Baseline, every 8 weeks until tumor progression or death ]
    Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed response were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. CR was defined as disappearance of all lesions (target and/or non target). PR were those with at least 30 percent decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non target lesions not increased or absent.
  • Duration of Response (DR) [ Time Frame: Baseline until death or at least 1 year after the randomization of last participant ]
    Time in weeks 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 due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7.
  • Change From Baseline in European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ- C30) Score [ Time Frame: Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal ]
    EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status (GHS), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea, and financial difficulties). Most questions used 4- point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores averaged, transformed to 0- 100 scale; higher score=better level of functioning or greater degree of symptoms. Change from baseline=Cycle/Day score minus baseline score.
  • Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Pancreatic 26 (EORTC QLQ- PAN26) Score [ Time Frame: Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal ]
    QLQ-PAN26 consists of 26 questions (Qs) relating to disease symptoms, treatment (Tx) side effects and emotional issues specific to pancreatic cancer (PC). Questions include on altered bowel habits, pain, dietary changes, disease and Tx-related symptoms and issues related to the emotional and social well-being of participants with PC. All 26 Qs are answered on 4-point Likert scale ranging from '1=not at all' to 4='very much' and subsequently transformed into scales that range from 0-100; higher scores= greater degree of symptoms or treatment side effects and emotional issues.
  • Change From Baseline Brief Pain Inventory-short Form (BPI-sf) Score [ Time Frame: Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal ]
    BPI-sf is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions. BPI-sf are 4 questions that assess pain intensity (worst, least, average, right now) and 7 questions that assess impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). Each question is answered on a scale ranging from 0 to 10; '0=No pain and 10=Pain as bad as you can imagine'. Measure can be scored by item, with lower scores being indicative of less pain or pain interference.
  • Change From Baseline in Euro QoL Questionnaire- 5 Dimension (EQ-5D) Health State Profile [ Time Frame: Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal ]
    EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (eg, "confined to bed"). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
  • Change From Baseline in Euro Qo

    Original Secondary Outcome:

    • Progression free survival (the time from randomization to first documentation of objective tumor progression or to death due to any cause, whichever occurs first).
    • Objective response rate (the proportion of patients with confirmed response according to RECIST, relative to all randomized patients who have baseline measurable disease).
    • Duration of response (the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first).
    • Safety and tolerability of AG-013736 plus gemcitabine. All patients who receive any study treatment will be included in the final summaries and listings of safety data.
    • Health-related quality of life, pain ratings, and health status of patients in each arm as measured by the Eur Org for the Res and Trtmnt of Cancer, Qual of Life Quest Core 30 and Pancreatic 26, BPI sf, and EQ 5D. [ Time Frame: Questionnaires will be completed prior to dosing and ideally before any clinical assessments. ]
    • Population pharmacokinetic analysis using AG-013736 plasma concentrations.


    Information By: Pfizer

    Dates:
    Date Received: May 7, 2007
    Date Started: July 2007
    Date Completion:
    Last Updated: June 14, 2012
    Last Verified: June 2012