Trial Outcomes & Findings for Gemcitabine Hydrochloride With or Without Erlotinib Hydrochloride Followed by the Same Chemotherapy Regimen With or Without Radiation Therapy and Capecitabine or Fluorouracil in Treating Patients With Pancreatic Cancer That Has Been Removed by Surgery (NCT NCT01013649)

Last Updated: 2025-10-08

Results Overview

Overall survival (OS) is estimated by the Kaplan-Meier method. Survival time is measured from step 2 randomization to date of death from any cause or last known follow-up (censored). Analysis was to occur at the earlier of 316 reported deaths or when all patients have five years potential follow-up from step 2 randomization.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

546 participants

Primary outcome timeframe

From step 2 randomization (chemotherapy vs. chemotherapy followed by chemoradiation) to the date of death or last follow-up. Maximum follow-up at time of the phase III analysis was 12.8 years, measured from step 2 randomization.

Results posted on

2025-10-08

Participant Flow

Participant milestones

Participant milestones
Measure	Arm I (Gemcitabine Hydrochloride or Combination Chemotherapy) Patients receive either gemcitabine hydrochloride or \[starting 06-28-2016\] allowable combination chemotherapy per standard of care for 5 months. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline.	Arm II (Gemcitabine Hydrochloride, Erlotinib Hydrochloride) \[Closed to accrual 2-28-2014.\] Patients receive gemcitabine hydrochloride IV over 30 minutes once a week for 3 weeks then off 1 week and erlotinib hydrochloride PO once daily on days 1-28. Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline.	Arm III (Chemotherapy) Patients receive the same treatment as in arm I or arm II for one month. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline.	Arm IV (Chemotherapy, Chemoradiotherapy) Patients receive the same treatment as in arm I or arm II for one month. Beginning within 7-21 days after completion of chemotherapy, patients undergo radiotherapy (3-dimensional conformal radiotherapy or intensity modulated radiotherapy) 5 days per week for 5.5 weeks (28 fractions). During radiotherapy, patients receive either capecitabine PO twice a day (BID) 5 days per week or fluorouracil IV continuously for 5.5 weeks or until radiotherapy is completed. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline.
First Step STARTED	379	167	0	0
First Step Randomized to Arm I or Arm II	169	167	0	0
First Step Registered to Arm 1 Only	210	0	0	0
First Step Eligible	363	159	0	0
First Step Phase II Analysis Population	163	159	0	0
First Step Phase II AE Population	160	158	0	0
First Step Randomized to Arm III	124	50	0	0
First Step Randomized to Arm IV	130	50	0	0
First Step COMPLETED	254	100	0	0
First Step NOT COMPLETED	125	67	0	0
Second Step STARTED	0	0	174	180
Second Step Phase III Analysis Population	0	0	174	180
Second Step Phase III AE Population	0	0	174	180
Second Step COMPLETED	0	0	174	180
Second Step NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm I (Gemcitabine Hydrochloride or Combination Chemotherapy) Patients receive either gemcitabine hydrochloride or \[starting 06-28-2016\] allowable combination chemotherapy per standard of care for 5 months. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline.	Arm II (Gemcitabine Hydrochloride, Erlotinib Hydrochloride) \[Closed to accrual 2-28-2014.\] Patients receive gemcitabine hydrochloride IV over 30 minutes once a week for 3 weeks then off 1 week and erlotinib hydrochloride PO once daily on days 1-28. Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline.
First Step Withdrawal by Subject	36	19
First Step Progression	58	23
First Step Did not start 5th cycle of first step treatment	15	10
First Step Death	3	4
First Step Adverse Event	9	5
First Step Other	4	6

Baseline Characteristics

Baseline characteristics are reported separately for phase II and phase III components.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Gemcitabine Hydrochloride or Combination Chemotherapy) n=163 Participants Patients receive either gemcitabine hydrochloride or \[starting 06-28-2016\] allowable combination chemotherapy per standard of care for 5 months. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline.	Arm II (Gemcitabine Hydrochloride, Erlotinib Hydrochloride) n=159 Participants \[Closed to accrual 2-28-2014.\] Patients receive gemcitabine hydrochloride IV over 30 minutes once a week for 3 weeks then off 1 week and erlotinib hydrochloride PO once daily on days 1-28. Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline.	Arm III (Chemotherapy) n=174 Participants Patients receive the same treatment as in arm I or arm II for one month. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline.	Arm IV (Chemotherapy, Chemoradiotherapy) n=180 Participants Patients receive the same treatment as in arm I or arm II for one month. Beginning within 7-21 days after completion of chemotherapy, patients undergo radiotherapy (3-dimensional conformal radiotherapy or intensity-modulated radiotherapy) 5 days per week for 5.5 weeks (28 fractions). During radiotherapy, patients receive either capecitabine PO BID 5 days per week or fluorouracil IV continuously for 5.5 weeks or until radiotherapy is completed. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline.	Total n=676 Participants Total of all reporting groups
Age, Customized Phase II Analysis · ≤ 49	18 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	17 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	35 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Age, Customized Phase II Analysis · 50 - 59	42 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	37 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	79 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Age, Customized Phase II Analysis · 60 - 69	57 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	59 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	116 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Age, Customized Phase II Analysis · 70 - 79	35 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	41 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	76 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Age, Customized Phase II Analysis · ≥ 80	11 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	5 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	16 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Age, Customized Phase III analysis · ≤ 49	—	—	17 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	16 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	33 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Age, Customized Phase III analysis · 50 - 59	—	—	44 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	44 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	88 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Age, Customized Phase III analysis · 60 - 69	—	—	63 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	72 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	135 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Age, Customized Phase III analysis · 70 - 79	—	—	43 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	40 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	83 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Age, Customized Phase III analysis · ≥ 80	—	—	7 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	8 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	15 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Sex: Female, Male Phase II analysis · Female	75 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	63 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	138 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Sex: Female, Male Phase II analysis · Male	88 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	96 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	184 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Sex: Female, Male Phase III analysis · Female	—	—	74 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	85 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	159 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Sex: Female, Male Phase III analysis · Male	—	—	100 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	95 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	195 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Ethnicity (NIH/OMB) Phase II analysis · Hispanic or Latino	10 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	8 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	18 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Ethnicity (NIH/OMB) Phase II analysis · Not Hispanic or Latino	143 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	143 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	286 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Ethnicity (NIH/OMB) Phase II analysis · Unknown or Not Reported	10 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	8 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	18 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Ethnicity (NIH/OMB) Phase III analysis · Hispanic or Latino	—	—	10 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	14 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	24 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Ethnicity (NIH/OMB) Phase III analysis · Not Hispanic or Latino	—	—	158 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	162 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	320 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Ethnicity (NIH/OMB) Phase III analysis · Unknown or Not Reported	—	—	6 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	4 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	10 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Race (NIH/OMB) Phase II analysis · American Indian or Alaska Native	0 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	1 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	1 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Race (NIH/OMB) Phase II analysis · Asian	4 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	4 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	8 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Race (NIH/OMB) Phase II analysis · Native Hawaiian or Other Pacific Islander	1 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	0 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	1 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Race (NIH/OMB) Phase II analysis · Black or African American	10 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	22 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	32 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Race (NIH/OMB) Phase II analysis · White	144 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	129 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	273 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Race (NIH/OMB) Phase II analysis · More than one race	0 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	0 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	0 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Race (NIH/OMB) Phase II analysis · Unknown or Not Reported	4 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	3 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	7 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Race (NIH/OMB) Phase III analysis · American Indian or Alaska Native	—	—	1 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	1 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	2 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Race (NIH/OMB) Phase III analysis · Asian	—	—	4 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	8 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	12 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Race (NIH/OMB) Phase III analysis · Native Hawaiian or Other Pacific Islander	—	—	0 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	2 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	2 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Race (NIH/OMB) Phase III analysis · Black or African American	—	—	19 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	27 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	46 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Race (NIH/OMB) Phase III analysis · White	—	—	147 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	139 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	286 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Race (NIH/OMB) Phase III analysis · More than one race	—	—	0 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	0 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	0 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Race (NIH/OMB) Phase III analysis · Unknown or Not Reported	—	—	3 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	3 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	6 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Tumor size largest dimension Phase II analysis	3.0 centimeters n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	3.0 centimeters n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	3.0 centimeters n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Tumor size largest dimension Phase III analysis	—	—	3.0 centimeters n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	3.0 centimeters n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	3.0 centimeters n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Zubrod Performance Status Phase II analysis · 0	65 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	78 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	143 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Zubrod Performance Status Phase II analysis · 1	98 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	81 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	179 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Zubrod Performance Status Phase III analysis · 0	—	—	72 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	83 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	155 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Zubrod Performance Status Phase III analysis · 1	—	—	102 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	97 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	199 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Histologic Type Phase II analysis · Adenocarcinoma	154 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	153 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	307 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Histologic Type Phase II analysis · Intraductal papillary mucinous neoplasm with invasive adenocarcinoma	9 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	6 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	15 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Histologic Type Phase III analysis · Adenocarcinoma	—	—	166 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	172 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	338 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Histologic Type Phase III analysis · Intraductal papillary mucinous neoplasm with invasive adenocarcinoma	—	—	8 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	8 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	16 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Pathologic T-Stage Phase II analysis · T1	7 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	8 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	15 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Pathologic T-Stage Phase II analysis · T2	30 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	25 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	55 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Pathologic T-Stage Phase II analysis · T3	126 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	126 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	252 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Pathologic T-Stage Phase III analysis · T1	—	—	2 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	12 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	14 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Pathologic T-Stage Phase III analysis · T2	—	—	27 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	25 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	52 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Pathologic T-Stage Phase III analysis · T3	—	—	145 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	143 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	288 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Pathologic N-Stage Phase II analysis · N0	45 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	40 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	85 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Pathologic N-Stage Phase II analysis · N1	118 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	119 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	237 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Pathologic N-Stage Phase III analysis · N0	—	—	42 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	49 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	91 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Pathologic N-Stage Phase III analysis · N1	—	—	132 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	131 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	263 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Number of Positive Lymph Nodes Phase II analysis · 0	45 Participants n=163 Participants • Baseline characteristics are reported separately for phase II analysis and phase III analysis.	40 Participants n=159 Participants • Baseline characteristics are reported separately for phase II analysis and phase III analysis.	—	—	85 Participants n=322 Participants • Baseline characteristics are reported separately for phase II analysis and phase III analysis.
Number of Positive Lymph Nodes Phase II analysis · 1-3	76 Participants n=163 Participants • Baseline characteristics are reported separately for phase II analysis and phase III analysis.	78 Participants n=159 Participants • Baseline characteristics are reported separately for phase II analysis and phase III analysis.	—	—	154 Participants n=322 Participants • Baseline characteristics are reported separately for phase II analysis and phase III analysis.
Number of Positive Lymph Nodes Phase II analysis · >3	42 Participants n=163 Participants • Baseline characteristics are reported separately for phase II analysis and phase III analysis.	41 Participants n=159 Participants • Baseline characteristics are reported separately for phase II analysis and phase III analysis.	—	—	83 Participants n=322 Participants • Baseline characteristics are reported separately for phase II analysis and phase III analysis.
Number of Positive Lymph Nodes Phase III analysis · 0	—	—	42 Participants n=174 Participants • Baseline characteristics are reported separately for phase II analysis and phase III analysis.	49 Participants n=180 Participants • Baseline characteristics are reported separately for phase II analysis and phase III analysis.	91 Participants n=354 Participants • Baseline characteristics are reported separately for phase II analysis and phase III analysis.
Number of Positive Lymph Nodes Phase III analysis · 1-3	—	—	95 Participants n=174 Participants • Baseline characteristics are reported separately for phase II analysis and phase III analysis.	79 Participants n=180 Participants • Baseline characteristics are reported separately for phase II analysis and phase III analysis.	174 Participants n=354 Participants • Baseline characteristics are reported separately for phase II analysis and phase III analysis.
Number of Positive Lymph Nodes Phase III analysis · >3	—	—	37 Participants n=174 Participants • Baseline characteristics are reported separately for phase II analysis and phase III analysis.	52 Participants n=180 Participants • Baseline characteristics are reported separately for phase II analysis and phase III analysis.	89 Participants n=354 Participants • Baseline characteristics are reported separately for phase II analysis and phase III analysis.
Carbohydrate antigen 19-9 (CA19-9) Level Phase II analysis · ≤ 90	152 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	148 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	300 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Carbohydrate antigen 19-9 (CA19-9) Level Phase II analysis · >90-180	11 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	11 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	22 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Carbohydrate antigen 19-9 (CA19-9) Level Phase III analysis · ≤ 90	—	—	163 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	177 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	340 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Carbohydrate antigen 19-9 (CA19-9) Level Phase III analysis · >90-180	—	—	11 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	3 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	14 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Surgical margins Phase II analysis · Positive	27 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	26 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	53 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Surgical margins Phase II analysis · Negative	136 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	133 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	269 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Surgical margins Phase III analysis · Positive	—	—	30 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	29 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	59 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Surgical margins Phase III analysis · Negative	—	—	144 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	151 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	295 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Type of surgery (phase III only) Phase II analysis · Classic Pancreaticoduodenectomy (Whipple)	123 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	117 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	240 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Type of surgery (phase III only) Phase II analysis · Pylorus preserving pancreaticoduodenectomy	40 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	40 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	80 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Type of surgery (phase III only) Phase II analysis · Other	0 Participants n=163 Participants • Baseline characteristics are reported separately for phase II and phase III components.	2 Participants n=159 Participants • Baseline characteristics are reported separately for phase II and phase III components.	—	—	2 Participants n=322 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Type of surgery (phase III only) Phase III analysis · Classic Pancreaticoduodenectomy (Whipple)	—	—	121 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	139 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	260 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Type of surgery (phase III only) Phase III analysis · Pylorus preserving pancreaticoduodenectomy	—	—	52 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	41 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	93 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Type of surgery (phase III only) Phase III analysis · Other	—	—	1 Participants n=174 Participants • Baseline characteristics are reported separately for phase II and phase III components.	0 Participants n=180 Participants • Baseline characteristics are reported separately for phase II and phase III components.	1 Participants n=354 Participants • Baseline characteristics are reported separately for phase II and phase III components.
Adjuvant Systemic Treatment (Phase III only) Gemcitabine alone	—	—	116 Participants n=174 Participants • Not reported for phase II analysis.	120 Participants n=180 Participants • Not reported for phase II analysis.	236 Participants n=354 Participants • Not reported for phase II analysis.
Adjuvant Systemic Treatment (Phase III only) Gemcitabine + Erlotinib	—	—	50 Participants n=174 Participants • Not reported for phase II analysis.	50 Participants n=180 Participants • Not reported for phase II analysis.	100 Participants n=354 Participants • Not reported for phase II analysis.
Adjuvant Systemic Treatment (Phase III only) Non-oxaliplatin gemcitabine combinations	—	—	8 Participants n=174 Participants • Not reported for phase II analysis.	10 Participants n=180 Participants • Not reported for phase II analysis.	18 Participants n=354 Participants • Not reported for phase II analysis.
Adjuvant Systemic Treatment (Phase III only) FOLFIRINOX or mFOLFIRINOX	—	—	0 Participants n=174 Participants • Not reported for phase II analysis.	0 Participants n=180 Participants • Not reported for phase II analysis.	0 Participants n=354 Participants • Not reported for phase II analysis.

PRIMARY outcome

Timeframe: From step 1 randomization (gemcitabine vs. gemcitabine/erlotinib) to death or last follow-up. Maximum follow-up at the time of the phase II analysis was 6.2 years.

Population: Eligible participants randomized at step 1.

Outcome measures

Outcome measures
Measure	Arm I (Gemcitabine Hydrochloride or Combination Chemotherapy) n=163 Participants Patients receive either gemcitabine hydrochloride or \[starting 6-28-2016\] allowable combination chemotherapy per standard of care for 5 months. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline.	Arm II (Gemcitabine Hydrochloride, Erlotinib Hydrochloride) n=159 Participants \[Closed to accrual 2-28-14.\] Patients receive gemcitabine hydrochloride IV over 30 minutes once a week for 3 weeks then off 1 week and erlotinib hydrochloride PO once daily on days 1-28. Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline.
Overall Survival (Percentage of Participants Alive) [Phase II]	29.9 months Interval 21.7 to 33.4	28.1 months Interval 20.7 to 30.9

PRIMARY outcome

Timeframe: From step 2 randomization (chemotherapy vs. chemotherapy followed by chemoradiation) to the date of death or last follow-up. Maximum follow-up at time of the phase III analysis was 12.8 years, measured from step 2 randomization.

Population: Participants randomized at step 2.

Outcome measures

Outcome measures
Measure	Arm I (Gemcitabine Hydrochloride or Combination Chemotherapy) n=174 Participants Patients receive either gemcitabine hydrochloride or \[starting 6-28-2016\] allowable combination chemotherapy per standard of care for 5 months. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline.	Arm II (Gemcitabine Hydrochloride, Erlotinib Hydrochloride) n=180 Participants \[Closed to accrual 2-28-14.\] Patients receive gemcitabine hydrochloride IV over 30 minutes once a week for 3 weeks then off 1 week and erlotinib hydrochloride PO once daily on days 1-28. Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline.
Overall Survival (Percentage of Participants Alive) [Phase III]	31.1 months Interval 25.3 to 37.6	27.3 months Interval 24.5 to 31.7

SECONDARY outcome

Timeframe: From step1 randomization (gemcitabine vs. gemcitabine/erlotinib) to disease event, death, or last follow-up. Maximum follow-up at the time of the phase II analysis was 6.2 years.

Population: Eligible participants randomized at step 1.

Disease-free survival is estimated by the Kaplan-Meier method. Disease-free survival time is measured from step 1 randomization to the first date of local or regional disease, distant metastases, second primary tumor, death due to any cause, or last known follow-up (censored). Analysis was to occur after 200 deaths were reported.

Outcome measures

Outcome measures
Measure	Arm I (Gemcitabine Hydrochloride or Combination Chemotherapy) n=163 Participants Patients receive either gemcitabine hydrochloride or \[starting 6-28-2016\] allowable combination chemotherapy per standard of care for 5 months. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline.	Arm II (Gemcitabine Hydrochloride, Erlotinib Hydrochloride) n=159 Participants \[Closed to accrual 2-28-14.\] Patients receive gemcitabine hydrochloride IV over 30 minutes once a week for 3 weeks then off 1 week and erlotinib hydrochloride PO once daily on days 1-28. Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline.
Disease-free Survival (Percentage of Participants Alive Without Disease) [Phase II]	12.7 months Interval 10.8 to 15.7	12.4 months Interval 9.7 to 16.5

SECONDARY outcome

Timeframe: From step 2 randomization (chemotherapy vs. chemotherapy followed by chemoradiation) to disease event, death, or last follow-up. Maximum follow-up at time of the phase III analysis was 12.8 years, measured from step 2 randomization.

Population: Participants randomized at step 2.

Disease-free survival is estimated by the Kaplan-Meier method. Disease-free survival time is measured from step 2 randomization to the first date of local or regional disease, distant metastases, second primary tumor, death due to any cause, or last known follow-up (censored). Analysis was to occur at the earlier of 316 reported deaths or when all participants have five years potential follow-up from second step randomization.

Outcome measures

Outcome measures
Measure	Arm I (Gemcitabine Hydrochloride or Combination Chemotherapy) n=174 Participants Patients receive either gemcitabine hydrochloride or \[starting 6-28-2016\] allowable combination chemotherapy per standard of care for 5 months. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline.	Arm II (Gemcitabine Hydrochloride, Erlotinib Hydrochloride) n=180 Participants \[Closed to accrual 2-28-14.\] Patients receive gemcitabine hydrochloride IV over 30 minutes once a week for 3 weeks then off 1 week and erlotinib hydrochloride PO once daily on days 1-28. Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline.
Disease-free Survival (Percentage of Participants Alive Without Disease) [Phase III]	12.4 months Interval 9.6 to 15.2	15.6 months Interval 13.2 to 18.8

SECONDARY outcome

Timeframe: From step 1 randomization (gemcitabine vs. gemcitabine/erlotinib) to death or last follow-up. Maximum follow-up at the time of the phase II analysis was 6.2 years.

Population: Eligible participants randomized in Step 1 who started protocol treatment and were assessed for adverse events.

Assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 which grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.

Outcome measures

Outcome measures
Measure	Arm I (Gemcitabine Hydrochloride or Combination Chemotherapy) n=160 Participants Patients receive either gemcitabine hydrochloride or \[starting 6-28-2016\] allowable combination chemotherapy per standard of care for 5 months. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline.	Arm II (Gemcitabine Hydrochloride, Erlotinib Hydrochloride) n=158 Participants \[Closed to accrual 2-28-14.\] Patients receive gemcitabine hydrochloride IV over 30 minutes once a week for 3 weeks then off 1 week and erlotinib hydrochloride PO once daily on days 1-28. Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline.
Number of Participants by Highest Grade Adverse Event Reported (Phase II) Grade 1	6 Participants	3 Participants
Number of Participants by Highest Grade Adverse Event Reported (Phase II) Grade 2	20 Participants	24 Participants
Number of Participants by Highest Grade Adverse Event Reported (Phase II) Grade 3	100 Participants	101 Participants
Number of Participants by Highest Grade Adverse Event Reported (Phase II) Grade 4	32 Participants	27 Participants
Number of Participants by Highest Grade Adverse Event Reported (Phase II) Grade 5	2 Participants	3 Participants

SECONDARY outcome

Timeframe: From step 2 randomization (chemotherapy vs. chemotherapy followed by chemoradiation) to death or last follow-up. Maximum follow-up at time of the phase III analysis was 12.8 years, measured from step 2 randomization.

Population: Participants randomized at step 2.

Assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 which grades adverse event severity from 1=mild to 5=death.

Outcome measures

Outcome measures
Measure	Arm I (Gemcitabine Hydrochloride or Combination Chemotherapy) n=174 Participants Patients receive either gemcitabine hydrochloride or \[starting 6-28-2016\] allowable combination chemotherapy per standard of care for 5 months. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline.	Arm II (Gemcitabine Hydrochloride, Erlotinib Hydrochloride) n=180 Participants \[Closed to accrual 2-28-14.\] Patients receive gemcitabine hydrochloride IV over 30 minutes once a week for 3 weeks then off 1 week and erlotinib hydrochloride PO once daily on days 1-28. Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline.
Number of Participants by Highest Grade Adverse Event Reported (Phase III) Grade 1	22 Participants	16 Participants
Number of Participants by Highest Grade Adverse Event Reported (Phase III) Grade 2	50 Participants	56 Participants
Number of Participants by Highest Grade Adverse Event Reported (Phase III) Grade 3	67 Participants	79 Participants
Number of Participants by Highest Grade Adverse Event Reported (Phase III) Grade 4	21 Participants	23 Participants
Number of Participants by Highest Grade Adverse Event Reported (Phase III) Grade 5	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From enrollment to death or last follow-up.

Overall survival is estimated by the Kaplan-Meier method. Survival time is measured from step 1 randomization to date of death from any cause or last known follow-up (censored). Baseline fatigue is measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACT-F) questionnaire which has a range of 0 to 52 with a higher score indicating less fatigue. Patients with low fatigue at baseline (FACIT-F score \> 30) will be compared to patients with high fatigue at baseline (FACIT-F scores ≤ 30). The analysis population is all enrolled eligible participants who consented to the quality of life study component and who have baseline FACT-F data.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: From enrollment to death or last follow-up.

Baseline PROMIS Fatigue scores will be analyzed to determine if there is a cut point (adjusting for multiple comparisons) that correlates with overall survival using the log-rank statistic. The analysis population is all enrolled eligible participants who consented to the quality of life study component and who have baseline PROMIS data.

Outcome measures

Outcome data not reported

Adverse Events

Arm I (Gemcitabine Hydrochloride or Combination Chemotherapy)

Serious events: 38 serious events

Other events: 158 other events

Deaths: 103 deaths

Arm II (Gemcitabine Hydrochloride, Erlotinib Hydrochloride)

Serious events: 45 serious events

Other events: 157 other events

Deaths: 100 deaths

Arm III (Chemotherapy)

Serious events: 33 serious events

Other events: 173 other events

Deaths: 136 deaths

Arm IV (Chemotherapy, Chemoradiotherapy)

Serious events: 31 serious events

Other events: 179 other events

Deaths: 134 deaths

Serious adverse events

Other adverse events

Additional Information

Wendy Seiferheld

NRG Oncology

Phone: 2155743208

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60