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

Brief summary public domain (ClinicalTrials.gov)

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 description public domain (ClinicalTrials.gov)

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.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Overall Survival (OS) [Baseline until death or at least 1 year after the randomization of last participant]. Median, Weeks (95% Confidence Interval). Axitinib + Gemcitabine (n=314): 36.9 (30.1 to 41.1); Placebo + Gemcitabine (n=316): 35.8 (30.0 to 44.8). Analysis, Axitinib + Gemcitabine vs Placebo + Gemcitabine: Hazard Ratio (HR) 1.014 (95% CI 0.786 to 1.309); p=0.5436; Log Rank; superiority or other.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Progression Free Survival (PFS) [Baseline until disease progression or at least 1 year after the randomization of last participant]. Median, Weeks (95% Confidence Interval). Axitinib + Gemcitabine (n=314): 19.1 (17.1 to 24.4); Placebo + Gemcitabine (n=316): 18.9 (16.2 to 22.6). Analysis, Axitinib + Gemcitabine vs Placebo + Gemcitabine: Hazard Ratio (HR) 1.006 (95% CI 0.779 to 1.298); p=0.5203; Log Rank; superiority or other.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Percentage of Participants With Objective Response (OR) [Baseline, every 8 weeks until tumor progression or death]. Number, Percentage of participants (95% Confidence Interval). Axitinib + Gemcitabine (n=314): 4.9 (2.5 to 8.3); Placebo + Gemcitabine (n=316): 1.6 (0.4 to 4.0). Analysis, Axitinib + Gemcitabine vs Placebo + Gemcitabine: Risk Ratio (RR) 3.2 (95% CI 1.0 to 10.1); p=0.038; Cochran-Mantel-Haenszel; superiority or other.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Duration of Response (DR) [Baseline until death or at least 1 year after the randomization of last participant]. Median, Weeks (95% Confidence Interval). Axitinib + Gemcitabine (n=12): 33.1 (16.1 to 33.1); Placebo + Gemcitabine (n=4): NA (NA to NA) [Median duration of response for placebo+gemcitabine arm did not reach at the time of data cut-off.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Change From Baseline in European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ- C30) Score [Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal]. Mean, Units on a scale (Standard Deviation). Physical functioning: Baseline (n=295, 289): Axitinib + Gemcitabine (n=314): 77.445 (20.3052); Placebo + Gemcitabine (n=316): 78.546 (18.9192). Physical functioning: Change at C2 D1 (n=233, 233): Axitinib + Gemcitabine (n=314): -2.713 (16.7682); Placebo + Gemcitabine (n=316): -3.261 (15.0742). Physical functioning: Change at C3 D1 (n=173, 179): Axitinib + Gemcitabine (n=314): -5.897 (19.3522); Placebo + Gemcitabine (n=316): -1.565 (16.2738). Physical functioning: Change at C4 D1 (n=134, 133): Axitinib + Gemcitabine (n=314): -5.671 (18.8623); Placebo + Gemcitabine (n=316): -1.453 (17.1209). Physical functioning: Change at C5 D1 (n=96, 82): Axitinib + Gemcitabine (n=314): -2.498 (21.8687); Placebo + Gemcitabine (n=316): -0.076 (16.9709). Physical functioning: Change at C6 D1 (n=59, 58): Axitinib + Gemcitabine (n=314): -5.193 (19.6995); Placebo + Gemcitabine (n=316): -1.719 (15.5260). Physical functioning: Change at C7 D1 (n=38, 37): Axitinib + Gemcitabine (n=314): -1.924 (14.2726); Placebo + Gemcitabine (n=316): 0.011 (18.9261). Physical functioning: Change at C8 D1 (n=15, 21): Axitinib + Gemcitabine (n=314): -4.000 (16.8759); Placebo + Gemcitabine (n=316): 0.014 (13.8428). Physical functioning: Change at C9 D1 (n=9, 9): Axitinib + Gemcitabine (n=314): 0.033 (15.2534); Placebo + Gemcitabine (n=316): -12.578 (20.9490). Physical functioning: Change at C10 D1 (n=3, 4): Axitinib + Gemcitabine (n=314): 6.667 (17.5754); Placebo + Gemcitabine (n=316): -1.675 (22.0563). Physical functioning: Change at C11 D1 (n=1, 1): Axitinib + Gemcitabine (n=314): 0.000 (NA) [Standard deviation was not estimable since only one participant was evaluable.]; Placebo + Gemcitabine (n=316): -6.600 (NA) [Standard deviation was not estimable since only one participant was evaluable.]. Physical functioning: Change at C12 D1 (n=1, 0): Axitinib + Gemcitabine (n=314): 0.000 (NA) [Standard deviation was not estimable since only one participant was evaluable.]; Placebo + Gemcitabine (n=316): NA (NA) [Data was not analyzed as no participants were evaluable for the particular cycle.]. Physical functioning: Change at C13 D1 (n=1, 0): Axitinib + Gemcitabine (n=314): 0.000 (NA) [Standard deviation was not estimable since only one participant was evaluable.]; Placebo + Gemcitabine (n=316): NA (NA) [Data was not analyzed as no participants were evaluable for the particular cycle.]. Physical functioning:Change at followup (n=67, 70): Axitinib + Gemcitabine (n=314): -17.713 (23.8263); Placebo + Gemcitabine (n=316): -11.523 (21.0513). Role functioning: Baseline (n=297, 295): Axitinib + Gemcitabine (n=314): 66.3 (30.09); Placebo + Gemcitabine (n=316): 68.1 (30.72). Role functioning: Change at C2 D

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Pancreatic 26 (EORTC QLQ- PAN26) Score [Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal]. Mean, Units on a scale (Standard Deviation). Pancreatic Pain: Baseline (n=246, 250): Axitinib + Gemcitabine (n=314): 41.6 (27.16); Placebo + Gemcitabine (n=316): 40.0 (25.54). Pancreatic Pain: Change at C2 D1 (n=191, 197): Axitinib + Gemcitabine (n=314): -10.9 (24.38); Placebo + Gemcitabine (n=316): -10.1 (22.93). Pancreatic Pain: Change at C3 D1 (n=141, 153): Axitinib + Gemcitabine (n=314): -16.3 (25.51); Placebo + Gemcitabine (n=316): -11.2 (24.92). Pancreatic Pain: Change at C4 D1 (n=99, 111): Axitinib + Gemcitabine (n=314): -13.2 (28.70); Placebo + Gemcitabine (n=316): -11.4 (26.16). Pancreatic Pain: Change at C5 D1 (n=67, 64): Axitinib + Gemcitabine (n=314): -15.8 (28.06); Placebo + Gemcitabine (n=316): -13.0 (23.85). Pancreatic Pain: Change at C6 D1 (n=41, 43): Axitinib + Gemcitabine (n=314): -15.9 (25.47); Placebo + Gemcitabine (n=316): -13.0 (24.62). Pancreatic Pain: Change at C7 D1 (n=25, 25): Axitinib + Gemcitabine (n=314): -15.3 (28.02); Placebo + Gemcitabine (n=316): -15.0 (25.69). Pancreatic Pain: Change at C8 D1 (n=11, 11): Axitinib + Gemcitabine (n=314): -7.6 (27.76); Placebo + Gemcitabine (n=316): -9.8 (30.01). Pancreatic Pain: Change at C9 D1 (n=6, 6): Axitinib + Gemcitabine (n=314): -29.2 (31.06); Placebo + Gemcitabine (n=316): 0.0 (15.81). Pancreatic Pain: Change at C10 D1 (n=2, 3): Axitinib + Gemcitabine (n=314): -20.9 (29.49); Placebo + Gemcitabine (n=316): 5.6 (26.79). Pancreatic Pain: Change at C11 D1 (n=1, 1): Axitinib + Gemcitabine (n=314): 0.0 (NA) [Standard deviation was not estimable since only one participant was evaluable.]; Placebo + Gemcitabine (n=316): 0.0 (NA) [Standard deviation was not estimable since only one participant was evaluable.]. Pancreatic Pain: Change at C12 D1 (n=1, 0): Axitinib + Gemcitabine (n=314): 0.0 (NA) [Standard deviation was not estimable since only one participant was evaluable.]; Placebo + Gemcitabine (n=316): NA (NA) [Data was not analyzed as no participants were evaluable for the particular cycle.]. Pancreatic Pain: Change at C13 D1 (n=1, 0): Axitinib + Gemcitabine (n=314): 0.0 (NA) [Standard deviation was not estimable since only one participant was evaluable.]; Placebo + Gemcitabine (n=316): NA (NA) [Data was not analyzed as no participants were evaluable for the particular cycle.]. Pancreatic Pain: Change at follow-up (n=47, 46): Axitinib + Gemcitabine (n=314): -3.5 (29.59); Placebo + Gemcitabine (n=316): -3.6 (28.80). Hepatic: Baseline (n=245, 254): Axitinib + Gemcitabine (n=314): 10.2 (17.21); Placebo + Gemcitabine (n=316): 10.8 (17.59). Hepatic: Change at C2 D1 (n=193, 205): Axitinib + Gemcitabine (n=314): 0.3 (18.24); Placebo + Gemcitabine (n=316): -2.0 (17.67). Hepatic: Change at C3 D1 (n=142, 157): Axitinib + Gemcitab

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Change From Baseline Brief Pain Inventory-short Form (BPI-sf) Score [Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal]. Mean, Units on a scale (Standard Deviation). Worst Pain: Baseline (n=247, 250): Axitinib + Gemcitabine (n=314): 3.8 (2.84); Placebo + Gemcitabine (n=316): 3.7 (2.96). Worst Pain: Change at C2 D1 (n=192, 200): Axitinib + Gemcitabine (n=314): -0.7 (3.04); Placebo + Gemcitabine (n=316): -0.9 (2.84). Worst Pain: Change at C3 D1 (n=138, 151): Axitinib + Gemcitabine (n=314): -1.5 (3.09); Placebo + Gemcitabine (n=316): -0.9 (2.83). Worst Pain: Change at C4 D1 (n=99, 113): Axitinib + Gemcitabine (n=314): -1.0 (3.41); Placebo + Gemcitabine (n=316): -0.9 (3.09). Worst Pain: Change at C5 D1 (n=69, 64): Axitinib + Gemcitabine (n=314): -1.1 (3.43); Placebo + Gemcitabine (n=316): -1.2 (3.08). Worst Pain: Change at C6 D1 (n=41, 43): Axitinib + Gemcitabine (n=314): -0.9 (2.98); Placebo + Gemcitabine (n=316): -1.0 (3.17). Worst Pain: Change at C7 D1 (n=25, 26): Axitinib + Gemcitabine (n=314): -0.8 (2.27); Placebo + Gemcitabine (n=316): -0.9 (3.50). Worst Pain: Change at C8 D1 (n=12, 13): Axitinib + Gemcitabine (n=314): 0.8 (2.56); Placebo + Gemcitabine (n=316): -1.5 (3.20). Worst Pain: Change at C9 D1(n=6, 6): Axitinib + Gemcitabine (n=314): -1.8 (1.94); Placebo + Gemcitabine (n=316): -1.3 (1.51). Worst Pain: Change at C10 D1 (n=2, 3): Axitinib + Gemcitabine (n=314): -2.0 (2.83); Placebo + Gemcitabine (n=316): -0.3 (2.31). Worst Pain: Change at C11 D1 (n=1, 1): Axitinib + Gemcitabine (n=314): 0.0 (NA) [Standard deviation was not estimable since only one participant was evaluable.]; Placebo + Gemcitabine (n=316): 0.0 (NA) [Standard deviation was not estimable since only one participant was evaluable.]. Worst Pain: Change at C12 D1 (n=1, 0): Axitinib + Gemcitabine (n=314): 0.0 (NA) [Standard deviation was not estimable since only one participant was evaluable.]; Placebo + Gemcitabine (n=316): NA (NA) [Data was not analyzed as no participants were evaluable for the particular cycle.]. Worst Pain: Change at C13 D1 (n=1, 1): Axitinib + Gemcitabine (n=314): 0.0 (NA) [Standard deviation was not estimable since only one participant was evaluable.]; Placebo + Gemcitabine (n=316): -4.0 (NA) [Standard deviation was not estimable since only one participant was evaluable.]. Worst Pain: Change at follow-up (n=47, 46): Axitinib + Gemcitabine (n=314): 0.5 (3.08); Placebo + Gemcitabine (n=316): 0.0 (3.21). Pain in Last 24 Hours (hrs): Baseline (n=246, 248): Axitinib + Gemcitabine (n=314): 1.8 (1.92); Placebo + Gemcitabine (n=316): 1.7 (1.93). Pain in Last 24 hrs: Change at C2 D1 (n=193, 197): Axitinib + Gemcitabine (n=314): -0.2 (2.21); Placebo + Gemcitabine (n=316): -0.3 (1.92). Pain in Last 24 hrs: Change at C3 D1 (n=138, 150): Axitinib + Gemcitabine (n=314): -0.6 (2.01); Placebo + Gemcitabine (n=316): -0.3 (1.88). Pain in Last 24 hrs: Change at C4 D1 (n=99, 112): Axitinib + Gemcitabine (n=314): -0.3

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Change From Baseline in Euro QoL Questionnaire- 5 Dimension (EQ-5D) Health State Profile [Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal]. Mean, Units on a scale (Standard Deviation). Baseline (n=289, 290): Axitinib + Gemcitabine (n=314): 0.665 (0.2709); Placebo + Gemcitabine (n=316): 0.690 (0.2479). Change at C2 D1 (n=231, 240): Axitinib + Gemcitabine (n=314): 0.050 (0.2699); Placebo + Gemcitabine (n=316): 0.020 (0.2033). Change at C3 D1 (n=171, 178): Axitinib + Gemcitabine (n=314): 0.053 (0.2528); Placebo + Gemcitabine (n=316): 0.028 (0.2362). Change at C4 D1 (n=128, 131): Axitinib + Gemcitabine (n=314): 0.010 (0.2730); Placebo + Gemcitabine (n=316): 0.050 (0.2209). Change at C5 D1 (n=94, 80): Axitinib + Gemcitabine (n=314): 0.010 (0.2889); Placebo + Gemcitabine (n=316): 0.044 (0.2092). Change at C6 D1 (n=57, 57): Axitinib + Gemcitabine (n=314): 0.001 (0.2489); Placebo + Gemcitabine (n=316): 0.058 (0.2294). Change at C7 D1 (n=37, 36): Axitinib + Gemcitabine (n=314): 0.049 (0.1891); Placebo + Gemcitabine (n=316): 0.075 (0.1838). Change at C8 D1 (n=17, 20): Axitinib + Gemcitabine (n=314): -0.021 (0.2366); Placebo + Gemcitabine (n=316): 0.071 (0.2188). Change at C9 D1 (n=9, 9): Axitinib + Gemcitabine (n=314): 0.049 (0.1878); Placebo + Gemcitabine (n=316): 0.121 (0.3006). Change at C10 D1 (n=3, 4): Axitinib + Gemcitabine (n=314): 0.181 (0.2206); Placebo + Gemcitabine (n=316): 0.208 (0.3034). Change at C11 D1 (n=1, 1): Axitinib + Gemcitabine (n=314): 0.000 (NA) [Standard deviation was not estimable since only one participant was evaluable.]; Placebo + Gemcitabine (n=316): 0.058 (NA) [Standard deviation was not estimable since only one participant was evaluable.]. Change at C12 D1 (n=1, 0): Axitinib + Gemcitabine (n=314): 0.000 (NA) [Standard deviation was not estimable since only one participant was evaluable.]; Placebo + Gemcitabine (n=316): NA (NA) [Data was not analyzed as no participants were evaluable for the particular cycle.]. Change at C13 D1 (n=1, 1): Axitinib + Gemcitabine (n=314): 0.000 (NA) [Standard deviation was not estimable since only one participant was evaluable.]; Placebo + Gemcitabine (n=316): 0.470 (NA) [Standard deviation was not estimable since only one participant was evaluable.]. Change at follow-up (n=65, 73): Axitinib + Gemcitabine (n=314): -0.148 (0.3637); Placebo + Gemcitabine (n=316): -0.080 (0.3243).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Change From Baseline in Euro QoL Questionnaire- 5 Dimension (EQ-5D) VAS Score [Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal]. Mean, Millimeter (mm) (Standard Deviation). Baseline (n= 277, 281): Axitinib + Gemcitabine (n=314): 60.6 (23.67); Placebo + Gemcitabine (n=316): 62.6 (23.09). Change at Cycle 2 Day 1 (n= 223, 226): Axitinib + Gemcitabine (n=314): 1.0 (19.64); Placebo + Gemcitabine (n=316): -0.4 (20.42). Change at Cycle 3 Day 1 (n= 161, 171): Axitinib + Gemcitabine (n=314): 2.6 (22.30); Placebo + Gemcitabine (n=316): 1.1 (20.25). Change at Cycle 4 Day 1 (n=122, 128): Axitinib + Gemcitabine (n=314): 0.5 (22.38); Placebo + Gemcitabine (n=316): 3.2 (19.81). Change at Cycle 5 Day 1 (n= 90, 79): Axitinib + Gemcitabine (n=314): -0.3 (22.83); Placebo + Gemcitabine (n=316): 1.9 (19.40). Change at Cycle 6 Day 1 (n= 56, 56): Axitinib + Gemcitabine (n=314): 1.0 (24.63); Placebo + Gemcitabine (n=316): 3.7 (21.84). Change at Cycle 7 Day 1 (n= 36, 35): Axitinib + Gemcitabine (n=314): 2.6 (25.82); Placebo + Gemcitabine (n=316): 4.1 (22.52). Change at Cycle 8 Day 1 (n= 16, 19): Axitinib + Gemcitabine (n=314): 3.8 (23.21); Placebo + Gemcitabine (n=316): 9.6 (28.55). Change at Cycle 9 Day 1 (n= 9, 9): Axitinib + Gemcitabine (n=314): 22.2 (24.93); Placebo + Gemcitabine (n=316): 7.7 (20.00). Change at Cycle 10 Day 1 (n= 3, 4): Axitinib + Gemcitabine (n=314): 20.0 (26.46); Placebo + Gemcitabine (n=316): 6.3 (24.62). Change at Cycle 11 Day 1 (n= 1, 1): Axitinib + Gemcitabine (n=314): 0.0 (NA) [Standard deviation was not estimable since only one participant was evaluable.]; Placebo + Gemcitabine (n=316): 30.0 (NA) [Standard deviation was not estimable since only one participant was evaluable.]. Change at Cycle 12 Day 1 (n= 1, 0): Axitinib + Gemcitabine (n=314): 0.0 (NA) [Standard deviation was not estimable since only one participant was evaluable.]; Placebo + Gemcitabine (n=316): NA (NA) [Data was not analyzed as no participants were evaluable for the particular cycle.]. Change at Cycle 13 Day 1 (n= 1, 1): Axitinib + Gemcitabine (n=314): 0.0 (NA) [Standard deviation was not estimable since only one participant was evaluable.]; Placebo + Gemcitabine (n=316): 36.0 (NA) [Standard deviation was not estimable since only one participant was evaluable.]. Change at follow-up (n= 62, 68): Axitinib + Gemcitabine (n=314): -6.3 (24.07); Placebo + Gemcitabine (n=316): -4.8 (22.79).