A Dose-Escalation to Rash Study of Tarceva (Erlotinib) Plus Gemcitabine in Patients With Metastatic Pancreatic Cancer

Brief summary public domain (ClinicalTrials.gov)

This study will compare the efficacy and safety of escalating versus standard doses to rash of Tarceva, in combination with gemcitabine, in patients with metastatic pancreatic cancer. During a 4 week run-in period, all patients will receive Tarceva 100mg/day po plus gemcitabine 1000mg/m2 iv on days 1, 8,15 and 22. After 4 weeks, patients who have not developed rash, or only develop grade 1 rash, will be randomized to one of 2 groups. Group 1 will receive a starting dose of Tarceva 150mg po daily, increased in steps of 50mg every 2 weeks up to a maximum of 250mg/day po, until development of grade 2 rash or other dose-limiting toxicity. Group 2 will continue to receive Tarceva 100mg/day po. All patients will continue to receive gemcitabine 1000mg/m2 iv on days 1, 8 and 15 of each 4 week cycle. The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.

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

Percentage of Participants Who Died Assessed From Point of Randomization [Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months.]. Number, percentage of participants. G+E Standard Dose: Rash Grade < 2 (n=75): 81.3; G+E Escalating Dose: Rash Grade < 2 (n=70): 85.7.

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

OS Assessed From Point of Randomization [Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months.]. Median, months (95% Confidence Interval). G+E Standard Dose: Rash Grade < 2 (n=75): 8.4 (6.4 to 10.0); G+E Escalating Dose: Rash Grade < 2 (n=70): 7.0 (5.8 to 8.3). Analysis, G+E Standard Dose: Rash Grade < 2 vs G+E Escalating Dose: Rash Grade < 2: Hazard Ratio (HR) 1.26 (95% CI 0.88 to 1.80); p=0.2026; Log Rank; superiority or other.

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

Percentage of Participants With Disease Progression or Death as Assessed From Point of Randomization [Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months.]. Number, percentage of participants. G+E Standard Dose: Rash Grade < 2 (n=75): 90.7; G+E Escalating Dose: Rash Grade < 2 (n=70): 88.6.

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

PFS Assessed From Point of Randomization [Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months.]. Median, weeks (95% Confidence Interval). G+E Standard Dose: Rash Grade < 2 (n=75): 19.4 (16.0 to 26.9); G+E Escalating Dose: Rash Grade < 2 (n=70): 15.3 (11.3 to 19.1). Analysis, G+E Standard Dose: Rash Grade < 2 vs G+E Escalating Dose: Rash Grade < 2: Hazard Ratio (HR) 1.09 (95% CI 0.77 to 1.54); p=0.6298; Log Rank; superiority or other.

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

Percentage of Participants With a Best Overall Response (BOR) of Confirmed Complete Response (CR) or Partial Response (PR) According to RECIST [BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression for up to 46 months.]. Number, percentage of participants (95% Confidence Interval). G+E Standard Dose: Rash Grade < 2 (n=75): 14.7 (7.6 to 24.7); G+E Escalating Dose: Rash Grade < 2 (n=70): 8.6 (3.2 to 17.7). Analysis, G+E Standard Dose: Rash Grade < 2 vs G+E Escalating Dose: Rash Grade < 2: Difference in Response Rates -6.10 (95% CI -17.2 to 5.0); p=0.2543; Chi-squared; superiority or other. Analysis, G+E Standard Dose: Rash Grade < 2 vs G+E Escalating Dose: Rash Grade < 2: Odds Ratio (OR) 0.55 (95% CI 0.19 to 1.56); superiority or other.

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

Percentage of Participants With a CR, PR, Stable Disease (SD), or PD According to RECIST [BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression for up to 46 months.]. Number, percentage of participants (95% Confidence Interval). CR: G+E Standard Dose: Rash Grade < 2 (n=75): 0.0 (0.0 to 4.8); G+E Escalating Dose: Rash Grade < 2 (n=70): 1.4 (0.0 to 7.7). PR: G+E Standard Dose: Rash Grade < 2 (n=75): 14.7 (7.6 to 24.7); G+E Escalating Dose: Rash Grade < 2 (n=70): 7.1 (2.4 to 15.9). SD: G+E Standard Dose: Rash Grade < 2 (n=75): 58.7 (46.7 to 69.9); G+E Escalating Dose: Rash Grade < 2 (n=70): 72.9 (60.9 to 82.8). PD: G+E Standard Dose: Rash Grade < 2 (n=75): 25.3 (16.0 to 36.7); G+E Escalating Dose: Rash Grade < 2 (n=70): 12.9 (6.1 to 23.0). Missing (no response assessment): G+E Standard Dose: Rash Grade < 2 (n=75): 1.3 (NA to NA) [95% CI was not determined for missing responses.]; G+E Escalating Dose: Rash Grade < 2 (n=70): 5.7 (NA to NA) [95% CI was not determined for missing responses.].

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

Percentage of Participants With SD (Maintained for at Least 8 Weeks) or CR or PR (Maintained for at Least 4 Weeks) According to RECIST [BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression for up to 46 months.]. Number, percentage of participants (95% Confidence Interval). G+E Standard Dose: Rash Grade < 2 (n=75): 62.7 (50.7 to 73.6); G+E Escalating Dose: Rash Grade < 2 (n=70): 47.1 (35.1 to 59.4). Analysis, G+E Standard Dose: Rash Grade < 2 vs G+E Escalating Dose: Rash Grade < 2: Difference in Disease Control Rates -15.52 (95% CI -32.4 to 1.3); p=0.0603; Chi-squared; superiority or other.

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

Percentage of Participants Who Died as Assessed From Start of 4-Week Run-In [BL and weekly thereafter for up to 46 months.]. Number, percentage of participants. G+E: Rash ≥ Grade 2 (n=106): 84.9; G+E Standard Dose: Rash Grade < 2 (n=75): 81.3; G+E Escalating Dose: Rash Grade < 2 (n=70): 85.7.

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

OS Assessed From Start of 4-Week Run-In [BL and weekly thereafter for up to 46 months.]. Median, months (95% Confidence Interval). G+E: Rash ≥ Grade 2 (n=106): 7.9 (7.1 to 8.8); G+E Standard Dose: Rash Grade < 2 (n=75): 9.3 (7.3 to 10.9); G+E Escalating Dose: Rash Grade < 2 (n=70): 8.0 (6.8 to 9.2). Analysis, G+E: Rash ≥ Grade 2 vs G+E Standard Dose: Rash Grade < 2: Hazard Ratio (HR) 0.83 (95% CI 0.60 to 1.15); p=0.2678; Log Rank; superiority or other. Analysis, G+E: Rash ≥ Grade 2 vs G+E Escalating Dose: Rash Grade < 2: Hazard Ratio (HR) 1.03 (95% CI 0.74 to 1.43); p=0.8449; Log Rank; superiority or other.

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

Percentage of Participants With Disease Progression or Death as Assessed From the Start of 4-Week Run-In [BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression or death for up to 46 months.]. Number, percentage of participants. G+E: Rash ≥ Grade 2 (n=106): 90.6; G+E Standard Dose: Rash Grade < 2 (n=75): 90.7; G+E Escalating Dose: Rash Grade < 2 (n=70): 88.6.

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

PFS Assessed From the Start of 4-Week Run-In [BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression or death for up to 46 months.]. Median, weeks (95% Confidence Interval). G+E: Rash ≥ Grade 2 (n=96): 17.1 (16.0 to 22.7); G+E Standard Dose: Rash Grade < 2 (n=68): 23.4 (20.0 to 31.0); G+E Escalating Dose: Rash Grade < 2 (n=62): 19.3 (15.3 to 23.1). Analysis, G+E: Rash ≥ Grade 2 vs G+E Standard Dose: Rash Grade < 2: Hazard Ratio (HR) 0.69 (95% CI 0.51 to 0.95); p=0.0217; Log Rank; superiority or other. Analysis, G+E: Rash ≥ Grade 2 vs G+E Escalating Dose: Rash Grade < 2: Hazard Ratio (HR) 0.79 (95% CI 0.57 to 1.10); p=0.1596; Log Rank; superiority or other.