A Dose-Escalation to Rash Study of Tarceva (Erlotinib) Pl... | NCT00652366

NCT00652366

ID	Type	Description	Link
2007-003751-37

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Gemcitabine, Erlotinib Standard Dose	Active Comparator	Participants received erlotinib, 100 milligrams (mg), orally (PO), once daily until disease progression or unacceptable toxicity. Participants also received gemcitabine, 1000 mg per (/) square meter (m^2), intravenously (IV), on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression or unacceptable toxicity.	Drug: Erlotinib, standard dose Drug: Gemcitabine
Gemcitabine, Erlotinib Escalating Dose	Experimental	Participants received erlotinib, beginning at 150 mg/day, PO, once daily, and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a grade 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal. Participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression or unacceptable toxicity.	Drug: Erlotinib, escalating dose Drug: Gemcitabine

Name	Type	Description	Arm Group Labels	Other Names
Erlotinib, escalating dose	Drug	100mg, PO, once daily, escalating to a maximum of 250mg, PO, once daily	Gemcitabine, Erlotinib Escalating Dose

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants Who Died Assessed From Point of Randomization	Overall survival (OS) assessed from the point of randomization was defined as the time from randomization to the date of death due to any cause. Participants still alive at the time of analysis were censored at the date they were last known to be alive.	Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months.
OS Assessed From Point of Randomization	OS assessed from the point of randomization was defined as the median time, in months, from randomization to the date of death due to any cause. Participants still alive at the time of analysis were censored at the date they were last known to be alive. The 95 percent (%) confidence interval (CI) was determined using Kaplan-Meier methodology.	Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months.

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Disease Progression or Death as Assessed From Point of Randomization	Progression-free survival (PFS) as assessed from the point of randomization was defined as the time from randomization to the first occurrence of progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors (RECIST) or death due to any cause. For target lesions (TLs), PD was defined as at least a 20% increase in the sum of longest diameter (SLD) of TLs, taking as reference the smallest SLD recorded since the treatment started. For non-target lesions (NTLs), PD was defined as unequivocal progression of existing NTLs. Participants who had neither progressed nor died at time of analysis were censored at the date of last tumor assessment.

Eligibility Module

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Gemcitabine (G) Plus (+) Erlotinib (E): Rash ≥ Grade 2	Participants began a 4 week run-in period where they received gemcitabine, 1000 milligrams per square meter (mg/m^2), intravenously (IV), on Days 1, 8, 15, 22 until development of a rash Grade ≥ 2. Participants also received erlotinib, 100 milligrams (mg), orally (PO) as a film-coated tablet, once daily until development of a rash Grade ≥ 2. Participants were not randomized to a treatment arm, but continued to receive the standard treatment of gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles, and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	G+E: Rash ≥ Grade 2	Participants began a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22 until development of a rash Grade ≥ 2. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily until development of a rash Grade ≥ 2. Participants were not randomized to a treatment arm, but continued to receive the standard treatment of gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles, and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
BG001	G+E Standard Dose: Rash Grade < 2	Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months.
BG002	G+E Escalating Dose: Rash Grade < 2	Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive erlotinib, beginning at 150 mg/day, PO as a film-coated tablet, once daily and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a Grade 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal for up to 46 months. Those participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
BG003	G+E: No Rash Non-Eligible	Participants began a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22 until the appearance of evidence of clinical progression or other toxicity leading to dose adjustments or discontinuation. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily until the appearance of evidence of clinical progression or other toxicity leading to dose adjustments or discontinuation. Participants were not randomized to a treatment arm, but continued to receive the standard treatment of gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles, and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
BG004	G+E: Early Drop Out	Participants began a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22 for up to 4 weeks. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for up to 4 weeks.
BG005	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants Who Died Assessed From Point of Randomization

Overall survival (OS) assessed from the point of randomization was defined as the time from randomization to the date of death due to any cause. Participants still alive at the time of analysis were censored at the date they were last known to be alive.

Full analysis set (FAS): all randomized participants.

Posted

Number

percentage of participants

Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months.

ID	Title	Description
OG000	G+E Standard Dose: Rash Grade < 2	Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months.
OG001	G+E Escalating Dose: Rash Grade < 2	Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive erlotinib, beginning at 150 mg/day, PO as a film-coated tablet, once daily and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a Grade 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal for up to 46 months. Those participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.

Units	Counts
Participants	OG00075 OG00170

Title

Denominators

Categories

Title	Measurements
	OG00081.3 OG00185.7

Primary

OS Assessed From Point of Randomization

OS assessed from the point of randomization was defined as the median time, in months, from randomization to the date of death due to any cause. Participants still alive at the time of analysis were censored at the date they were last known to be alive. The 95 percent (%) confidence interval (CI) was determined using Kaplan-Meier methodology.

FAS

Posted

Median

95% Confidence Interval

months

Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months.

ID	Title	Description
OG000	G+E Standard Dose: Rash Grade < 2	Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months
OG001	G+E Escalating Dose: Rash Grade < 2	Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive erlotinib, beginning at 150 mg/day, PO as a film-coated tablet, once daily and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a Grade 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal for up to 46 months. Those participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.

Secondary

Percentage of Participants With Disease Progression or Death as Assessed From Point of Randomization

Progression-free survival (PFS) as assessed from the point of randomization was defined as the time from randomization to the first occurrence of progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors (RECIST) or death due to any cause. For target lesions (TLs), PD was defined as at least a 20% increase in the sum of longest diameter (SLD) of TLs, taking as reference the smallest SLD recorded since the treatment started. For non-target lesions (NTLs), PD was defined as unequivocal progression of existing NTLs. Participants who had neither progressed nor died at time of analysis were censored at the date of last tumor assessment.

FAS

Posted

Number

percentage of participants

Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months.

ID	Title	Description
OG000	G+E Standard Dose: Rash Grade < 2	Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months.
OG001

Secondary

PFS Assessed From Point of Randomization

PFS assessed from the point of randomization was defined as the median time, in weeks, from randomization to disease progression or death due to any cause. Participants who had neither progressed nor died at time of analysis were censored at the date of last tumor assessment. The 95% CI was determined using Kaplan-Meier methodology.

FAS

Posted

Median

95% Confidence Interval

weeks

Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months.

ID	Title	Description
OG000	G+E Standard Dose: Rash Grade < 2	Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months.
OG001	G+E Escalating Dose: Rash Grade < 2	Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive erlotinib, beginning at 150 mg/day, PO as a film-coated tablet, once daily and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a Grade 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal for up to 46 months. Those participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.

Secondary

Percentage of Participants With a Best Overall Response (BOR) of Confirmed Complete Response (CR) or Partial Response (PR) According to RECIST

BOR was defined as a confirmed CR or PR for at least 4 weeks. CR was defined as the disappearance of all TLs. PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the baseline (BL) SLD. The 95% CI for one sample binomial was determined using Pearson-Clopper method.

FAS

Posted

Number

95% Confidence Interval

percentage of participants

BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression for up to 46 months.

ID	Title	Description
OG000	G+E Standard Dose: Rash Grade < 2	Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months.
OG001	G+E Escalating Dose: Rash Grade < 2	Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive erlotinib, beginning at 150 mg/day, PO as a film-coated tablet, once daily and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a Grade 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal for up to 46 months. Those participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.

Secondary

Percentage of Participants With a CR, PR, Stable Disease (SD), or PD According to RECIST

CR was defined as the disappearance of all TLs. PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the BL SLD SD was defined as neither sufficient decrease in SLD to qualify for PR nor sufficient increase in SLD to qualify for PD. PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since the treatment started. The 95% CI for one sample binomial was determined using the Pearson-Clopper method.

FAS

Posted

Number

95% Confidence Interval

percentage of participants

BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression for up to 46 months.

ID	Title	Description
OG000	G+E Standard Dose: Rash Grade < 2	Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months.
OG001	G+E Escalating Dose: Rash Grade < 2

Secondary

Percentage of Participants With SD (Maintained for at Least 8 Weeks) or CR or PR (Maintained for at Least 4 Weeks) According to RECIST

Disease control was defined as a participant with a response of CR or PR for at least 4 weeks at any time during treatment, or SD that was maintained for at least 8 weeks after the start of treatment. The 95% CI for one sample binomial was determined using the Pearson-Clopper method.

FAS

Posted

Number

95% Confidence Interval

percentage of participants

BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression for up to 46 months.

ID	Title	Description
OG000	G+E Standard Dose: Rash Grade < 2	Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months.
OG001	G+E Escalating Dose: Rash Grade < 2	Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive erlotinib, beginning at 150 mg/day, PO as a film-coated tablet, once daily and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a Grade 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal for up to 46 months. Those participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.

Secondary

Percentage of Participants Who Died as Assessed From Start of 4-Week Run-In

OS assessed from the start of the 4-week run in period was defined as the time from BL to the date of death due to any cause. Participants still alive at the time of analysis were censored at the date they were last known to be alive.

FAS

Posted

Number

percentage of participants

BL and weekly thereafter for up to 46 months.

ID	Title	Description
OG000	G+E: Rash ≥ Grade 2	Participants began a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22 until development of a rash Grade ≥ 2. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily until development of a rash Grade ≥ 2. Participants were not randomized to a treatment arm, but continued to receive the standard treatment of gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles, and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
OG001	G+E Standard Dose: Rash Grade < 2	Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months.

Secondary

OS Assessed From Start of 4-Week Run-In

OS assessed from the start of the 4-week run in period was defined as the median time, in months, from BL to the date of death, due to any cause. Participants who were still alive at the time of analysis were censored at the date they were last known to be alive. The 95% CI was determined using Kaplan-Meier methodology.

FAS

Posted

Median

95% Confidence Interval

months

BL and weekly thereafter for up to 46 months.

ID	Title	Description
OG000	G+E: Rash ≥ Grade 2	Participants began a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22 until development of a rash Grade ≥ 2. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily until development of a rash Grade ≥ 2. Participants were not randomized to a treatment arm, but continued to receive the standard treatment of gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles, and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
OG001	G+E Standard Dose: Rash Grade < 2	Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months.

Secondary

Percentage of Participants With Disease Progression or Death as Assessed From the Start of 4-Week Run-In

PFS as assessed from the start of 4-week run-in was defined as the time from BL to the first occurrence of PD according to RECIST or death due to any cause. For TLs, PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since the treatment started. For NTLs, PD was defined as unequivocal progression of existing NTLs. Participants who had neither progressed nor died at time of analysis were censored at the date of last tumor assessment.

FAS

Posted

Number

percentage of participants

BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression or death for up to 46 months.

ID	Title	Description
OG000	G+E: Rash ≥ Grade 2	Participants began a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22 until development of a rash Grade ≥ 2. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily until development of a rash Grade ≥ 2. Participants were not randomized to a treatment arm, but continued to receive the standard treatment of gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles, and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
OG001	G+E Standard Dose: Rash Grade < 2

Secondary

PFS Assessed From the Start of 4-Week Run-In

PFS assessed from the start of 4-week run-in was defined as the median time, in weeks, from BL to disease progression or death due to any cause. Participants who had neither progressed nor died at time of analysis were censored at the date of last tumor assessment. The 95% CI was determined using Kaplan-Meier methodology.

FAS; only participants with an event of PD or death were included in the analysis.

Posted

Median

95% Confidence Interval

weeks

BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression or death for up to 46 months.

ID	Title	Description
OG000	G+E: Rash ≥ Grade 2	Participants began a 4 week run-in period where they received gemcitabine, 1000 milligrams per square meter (mg/m^2), intravenously (IV), on Days 1, 8, 15, 22 until development of a rash Grade ≥ 2. Participants also received erlotinib, 100 milligrams (mg), orally (PO) as a film-coated tablet, once daily until development of a rash Grade ≥ 2. Participants were not randomized to a treatment arm, but continued to receive the standard treatment of gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles, and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
OG001	G+E Standard Dose: Rash Grade < 2	Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	G+E: Rash ≥ Grade 2	Participants began a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22 until development of a rash Grade ≥ 2. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily until development of a rash Grade ≥ 2. Participants were not randomized to a treatment arm, but continued to receive the standard treatment of gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles, and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.	39	105	105	105
EG001	G+E Standard Dose: Rash Grade < 2	Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months.	24	77	74	77
EG002	G+E Escalating Dose: Rash Grade < 2	Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive erlotinib, beginning at 150 mg/day, PO as a film-coated tablet, once daily and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a Grade 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal for up to 46 months. Those participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.	20	71	71	71
EG003	G+E: No Rash Non-Eligible	Participants began a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22 until the appearance of evidence of clinical progression or other toxicity leading to dose adjustments or discontinuation. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily until the appearance of evidence of clinical progression or other toxicity leading to dose adjustments or discontinuation. Participants were not randomized to a treatment arm, but continued to receive the standard treatment of gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles, and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.	64	178	178	178
EG004	G+E: Early Drop Out	Participants began a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22 for up to 4 weeks. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for up to 4 weeks.	22	36	34	36

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0003 affected105 at risk EG0010 affected77 at risk EG0021 affected71 at risk EG0034 affected178 at risk EG0042 affected36 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0002 affected105 at risk EG0014 affected77 at risk EG0021 affected71 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0002 affected105 at risk EG0011 affected77 at risk EG0021 affected71 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0021 affected71 at risk EG003
Ileus	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Peritonitis	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0002 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0021 affected71 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Duodenal ulcer	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Enteritis	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Faecaloma	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Gastric haemorrhage	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Intestinal fistula	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Jejunal perforation	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Melaena	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Obstruction gastric	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Oesophagitis haemorrhagic	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Skin oedema	Skin and subcutaneous tissue disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Central venous catheterisation	Surgical and medical procedures	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0021 affected71 at risk EG003
Face injury	Injury, poisoning and procedural complications	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0021 affected71 at risk EG003
Hip fracture	Injury, poisoning and procedural complications	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Blood glucose increased	Investigations	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0021 affected71 at risk EG003
Liver function test abnormal	Investigations	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Paraganglion neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Psychotic disorder	Psychiatric disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Suicide attempt	Psychiatric disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (14.0)	Non-systematic Assessment	EG0002 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0022 affected71 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0011 affected77 at risk EG0021 affected71 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Cardiac arrest	Cardiac disorders	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0011 affected77 at risk EG0020 affected71 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Renal failure acute	Renal and urinary disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Renal failure chronic	Renal and urinary disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0021 affected71 at risk EG003
Renal tubular necrosis	Renal and urinary disorders	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Pneumonia	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0012 affected77 at risk EG0021 affected71 at risk EG003
Infection	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Sepsis	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0002 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Cellulitis	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0011 affected77 at risk EG0020 affected71 at risk EG003
Biliary sepsis	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0021 affected71 at risk EG003
Bronchopneumonia	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0021 affected71 at risk EG003
Device related infection	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0021 affected71 at risk EG003
Escherichia sepsis	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0021 affected71 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Abdominal abscess	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0011 affected77 at risk EG0020 affected71 at risk EG003
Biliary tract infection	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0011 affected77 at risk EG0020 affected71 at risk EG003
Bronchitis	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0011 affected77 at risk EG0020 affected71 at risk EG003
Clostridial infection	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Erysipelas	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Febrile infection	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0021 affected71 at risk EG003
Gastrointestinal viral infection	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Klebsiella infection	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Orchitis	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0021 affected71 at risk EG003
Parainfluenzae virus infection	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Peritonitis bacterial	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0021 affected71 at risk EG003
Pyelonephritis acute	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Skin infection	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Subcutaneous abscess	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Superinfection	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Viral infection	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Vulvitis	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA (14.0)	Non-systematic Assessment	EG0004 affected105 at risk EG0011 affected77 at risk EG0022 affected71 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (14.0)	Non-systematic Assessment	EG0002 affected105 at risk EG0011 affected77 at risk EG0021 affected71 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Pyrexia	General disorders	MedDRA (14.0)	Non-systematic Assessment	EG0003 affected105 at risk EG0012 affected77 at risk EG0023 affected71 at risk EG003
General physical health deterioration	General disorders	MedDRA (14.0)	Non-systematic Assessment	EG0002 affected105 at risk EG0011 affected77 at risk EG0021 affected71 at risk EG003
Chills	General disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Death	General disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Device occlusion	General disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0021 affected71 at risk EG003
Fatigue	General disorders	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Malaise	General disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0011 affected77 at risk EG0020 affected71 at risk EG003
Oedema	General disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0021 affected71 at risk EG003
Oedema peripheral	General disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Pain	General disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0021 affected71 at risk EG003
Sudden death	General disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Ulcer haemorrhage	General disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0011 affected77 at risk EG0020 affected71 at risk EG003
Cholangitis	Hepatobiliary disorders	MedDRA (14.0)	Non-systematic Assessment	EG0002 affected105 at risk EG0011 affected77 at risk EG0022 affected71 at risk EG003
Bile duct obstruction	Hepatobiliary disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0011 affected77 at risk EG0020 affected71 at risk EG003
Jaundice	Hepatobiliary disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0021 affected71 at risk EG003
Cholangitis acute	Hepatobiliary disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0022 affected71 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Cholestasis	Hepatobiliary disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Hepatic failure	Hepatobiliary disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0002 affected105 at risk EG0010 affected77 at risk EG0021 affected71 at risk EG003
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0011 affected77 at risk EG0020 affected71 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Lung infiltration	Respiratory, thoracic and mediastinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Obliterative bronchiolitis	Respiratory, thoracic and mediastinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Ischaemic stroke	Nervous system disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0011 affected77 at risk EG0020 affected71 at risk EG003
Presyncope	Nervous system disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0011 affected77 at risk EG0020 affected71 at risk EG003
Cerebral haemorrhage	Nervous system disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Dizziness	Nervous system disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Haemorrhagic cerebral infarction	Nervous system disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Loss of consciousness	Nervous system disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Polyneuropathy	Nervous system disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Sensory loss	Nervous system disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Transient ischaemic attack	Nervous system disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0011 affected77 at risk EG0020 affected71 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0011 affected77 at risk EG0020 affected71 at risk EG003
Thrombosis	Vascular disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0011 affected77 at risk EG0021 affected71 at risk EG003
Axillary vein thrombosis	Vascular disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0011 affected77 at risk EG0020 affected71 at risk EG003
Embolism venous	Vascular disorders	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Hypertension	Vascular disorders	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Hypotension	Vascular disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0011 affected77 at risk EG0020 affected71 at risk EG003
Orthostatic hypotension	Vascular disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0010 affected77 at risk EG0020 affected71 at risk EG003
Phlebitis	Vascular disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0011 affected77 at risk EG0020 affected71 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG00049 affected105 at risk EG00133 affected77 at risk EG00235 affected71 at risk EG00371 affected178 at risk EG0049 affected36 at risk
Nausea	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG00050 affected105 at risk EG00128 affected77 at risk EG00224 affected71 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG00027 affected105 at risk EG00117 affected77 at risk EG00223 affected71 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG00026 affected105 at risk EG00113 affected77 at risk EG00216 affected71 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG00023 affected105 at risk EG00111 affected77 at risk EG00215 affected71 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG00010 affected105 at risk EG0016 affected77 at risk EG0025 affected71 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0003 affected105 at risk EG0013 affected77 at risk EG0022 affected71 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (14.0)	Non-systematic Assessment	EG00047 affected105 at risk EG00118 affected77 at risk EG00215 affected71 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA (14.0)	Non-systematic Assessment	EG00026 affected105 at risk EG00126 affected77 at risk EG00227 affected71 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA (14.0)	Non-systematic Assessment	EG00040 affected105 at risk EG00120 affected77 at risk EG00217 affected71 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA (14.0)	Non-systematic Assessment	EG0008 affected105 at risk EG0017 affected77 at risk EG0023 affected71 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA (14.0)	Non-systematic Assessment	EG000105 affected105 at risk EG00160 affected77 at risk EG00264 affected71 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (14.0)	Non-systematic Assessment	EG00010 affected105 at risk EG0017 affected77 at risk EG00210 affected71 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (14.0)	Non-systematic Assessment	EG0009 affected105 at risk EG0014 affected77 at risk EG00213 affected71 at risk EG003
Fatigue	General disorders	MedDRA (14.0)	Non-systematic Assessment	EG00032 affected105 at risk EG00117 affected77 at risk EG00223 affected71 at risk EG003
Pyrexia	General disorders	MedDRA (14.0)	Non-systematic Assessment	EG00029 affected105 at risk EG00122 affected77 at risk EG00215 affected71 at risk EG003
Asthenia	General disorders	MedDRA (14.0)	Non-systematic Assessment	EG00010 affected105 at risk EG00110 affected77 at risk EG00212 affected71 at risk EG003
Oedema peripheral	General disorders	MedDRA (14.0)	Non-systematic Assessment	EG00015 affected105 at risk EG00113 affected77 at risk EG0026 affected71 at risk EG003
Mucosal inflammation	General disorders	MedDRA (14.0)	Non-systematic Assessment	EG00010 affected105 at risk EG0018 affected77 at risk EG0028 affected71 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA (14.0)	Non-systematic Assessment	EG00031 affected105 at risk EG00117 affected77 at risk EG00224 affected71 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (14.0)	Non-systematic Assessment	EG0004 affected105 at risk EG0014 affected77 at risk EG0029 affected71 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG00014 affected105 at risk EG0017 affected77 at risk EG0027 affected71 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG00015 affected105 at risk EG0017 affected77 at risk EG0023 affected71 at risk EG003
Weight decreased	Investigations	MedDRA (14.0)	Non-systematic Assessment	EG0009 affected105 at risk EG0017 affected77 at risk EG00215 affected71 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA (14.0)	Non-systematic Assessment	EG0004 affected105 at risk EG0016 affected77 at risk EG0025 affected71 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (14.0)	Non-systematic Assessment	EG00013 affected105 at risk EG0018 affected77 at risk EG0028 affected71 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (14.0)	Non-systematic Assessment	EG0009 affected105 at risk EG0017 affected77 at risk EG00210 affected71 at risk EG003
Headache	Nervous system disorders	MedDRA (14.0)	Non-systematic Assessment	EG0002 affected105 at risk EG0018 affected77 at risk EG0024 affected71 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (14.0)	Non-systematic Assessment	EG0008 affected105 at risk EG0012 affected77 at risk EG0025 affected71 at risk EG003
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA (14.0)	Non-systematic Assessment	EG0001 affected105 at risk EG0011 affected77 at risk EG0024 affected71 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG00010 affected105 at risk EG0015 affected77 at risk EG0027 affected71 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG00010 affected105 at risk EG0013 affected77 at risk EG0023 affected71 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0004 affected105 at risk EG0011 affected77 at risk EG0025 affected71 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA (14.0)	Non-systematic Assessment	EG0005 affected105 at risk EG0014 affected77 at risk EG0022 affected71 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA (14.0)	Non-systematic Assessment	EG0003 affected105 at risk EG0015 affected77 at risk EG0025 affected71 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA (14.0)	Non-systematic Assessment	EG0002 affected105 at risk EG0014 affected77 at risk EG0023 affected71 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (14.0)	Non-systematic Assessment	EG0002 affected105 at risk EG0012 affected77 at risk EG0021 affected71 at risk EG003
Depression	Psychiatric disorders	MedDRA (14.0)	Non-systematic Assessment	EG0005 affected105 at risk EG0014 affected77 at risk EG0022 affected71 at risk EG003
Anxiety	Psychiatric disorders	MedDRA (14.0)	Non-systematic Assessment	EG0003 affected105 at risk EG0014 affected77 at risk EG0021 affected71 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA (14.0)	Non-systematic Assessment	EG0002 affected105 at risk EG0010 affected77 at risk EG0021 affected71 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA (14.0)	Non-systematic Assessment	EG0003 affected105 at risk EG0014 affected77 at risk EG0023 affected71 at risk EG003
Hypertension	Vascular disorders	MedDRA (14.0)	Non-systematic Assessment	EG0005 affected105 at risk EG0015 affected77 at risk EG0023 affected71 at risk EG003
General physical health deterioration	General disorders	MedDRA (14.0)	Non-systematic Assessment	EG0004 affected105 at risk EG0012 affected77 at risk EG0024 affected71 at risk EG003
Influenza like illness	General disorders	MedDRA (14.0)	Non-systematic Assessment	EG0007 affected105 at risk EG0012 affected77 at risk EG0022 affected71 at risk EG003
Pain	General disorders	MedDRA (14.0)	Non-systematic Assessment	EG0002 affected105 at risk EG0014 affected77 at risk EG0024 affected71 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0003 affected105 at risk EG0012 affected77 at risk EG0024 affected71 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (14.0)	Non-systematic Assessment	EG0000 affected105 at risk EG0011 affected77 at risk EG0023 affected71 at risk EG003
Dizziness	Nervous system disorders	MedDRA (14.0)	Non-systematic Assessment	EG0005 affected105 at risk EG0012 affected77 at risk EG0025 affected71 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA (14.0)	Non-systematic Assessment	EG0006 affected105 at risk EG0014 affected77 at risk EG0027 affected71 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (14.0)	Non-systematic Assessment	EG0008 affected105 at risk EG0012 affected77 at risk EG0021 affected71 at risk EG003

Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive erlotinib, beginning at 150 mg/day, PO as a film-coated tablet, once daily and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a Grade 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal for up to 46 months. Those participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.

Facility	Status	City	State	ZIP	Country	Contacts
		Buenos Aires		C1264AAA	Argentina

ID	Term
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004701	Endocrine Gland Neoplasms
D004066	Digestive System Diseases
D010182	Pancreatic Diseases
D004700	Endocrine System Diseases

ID	Term
D011799	Quinazolines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring