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

• Overall survival (first randomization) [ Time Frame: From the date of first randomization (gemcitabine vs. gemcitabine/erlotinib) to the date of death or last follow-up, assessed up to 11 years ] [ Designated as safety issue: No ]
  Overall survival will be estimated by the Kaplan-Meier method. The distribution of overall survival estimates between the two arms for both primary endpoint questions will be compared using the log rank test. The Cox proportional hazard regression model will be used to analyze the effects of factors, in addition to treatment, that may be associated with overall survival.
  
  
• Overall survival (second randomization) [ Time Frame: From the date of second randomization (chemotherapy vs. chemotherapy followed by chemoradiation) to the date of death or last follow-up, assessed up to 11 years ] [ Designated as safety issue: No ]
  Overall survival will be estimated by the Kaplan-Meier method. The distribution of overall survival estimates between the two arms for both primary endpoint questions will be compared using the log rank test. The Cox proportional hazard regression model will be used to analyze the effects of factors, in addition to treatment, that may be associated with overall survival.
  
  

• Disease-free survival [ Time Frame: Up to 11 years ] [ Designated as safety issue: No ]
  Disease-free survival will be estimated by the Kaplan-Meier method.
  
  
• Adverse events assessed according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 11 years ] [ Designated as safety issue: Yes ]
  
• Frequency of objective criteria of resectability as measured by preoperative imaging [ Time Frame: Up to 11 years ] [ Designated as safety issue: No ]
  

PRIMARY OBJECTIVES:

I. To determine whether the addition of erlotinib hydrochloride to adjuvant chemotherapy comprising gemcitabine hydrochloride improves survival as compared to gemcitabine hydrochloride alone following R0 or R1 resection in patients with pancreatic adenocarcinoma.

II. To determine whether the use of concurrent fluoropyrimidine and radiotherapy following adjuvant gemcitabine hydrochloride-based chemotherapy further enhances survival of patients who have no evidence of progressive disease after 5 courses of gemcitabine hydrochloride-based chemotherapy.

SECONDARY OBJECTIVES:

I. To evaluate the disease-free survival of patients who are disease-free after 5 courses of adjuvant gemcitabine hydrochloride-based chemotherapy followed by fluoropyrimidine-based chemoradiotherapy.

II. To evaluate the disease-free survival of patients treated with adjuvant gemcitabine hydrochloride-based chemotherapy with vs without erlotinib hydrochloride.

III. To evaluate the disease-free and overall survival of patients stratified by wild-type and K-Ras status treated with adjuvant gemcitabine hydrochloride-based chemotherapy with vs without erlotinib hydrochloride.

IV. To evaluate adverse events associated with adjuvant gemcitabine hydrochloride-based chemotherapy with vs without erlotinib hydrochloride in these patients.

V. To evaluate adverse events associated with adjuvant gemcitabine hydrochloride-based chemotherapy with vs without fluoropyrimidine-based chemoradiotherapy in patients who are disease-free after adjuvant gemcitabine hydrochloride-based chemotherapy.

VI. To evaluate preoperative cross-sectional imaging of primary adenocarcinoma of the head of the pancreas in order to determine the frequency with which objective criteria of resectability are present.

VII. To determine the predictive roles of K-Ras mutations and epithelial to mesenchymal transition phenotype in response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibition in early-stage pancreatic cancer.

VIII. To determine the frequency of EGFR-activated pathway and its influence on outcome.

IX. To determine the association between developmental molecular markers and outcome.

X. To determine the phenotype and genotype of tumors in patients with recurrence after resection.

XI. To determine if low baseline fatigue, as measured by the FACIT-Fatigue, predicts survival.

XII. To explore correlations between baseline fatigue, as measured by PROMIS, and survival.

OUTLINE: This is a multicenter study. Patients are stratified according to nodal status (involved vs uninvolved), CA19-9 result (≤ 90 IU/L vs 91-180 IU/L), and surgical margins (positive [R1] vs negative [R0]). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 5 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive gemcitabine hydrochloride as in arm I and oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats every 28 days for 5 courses in the absence of disease progression or unacceptable toxicity. Patients with no disease progression after treatment in arm I or II are then stratified according to their first randomization treatment arm (arm I vs arm II) and randomized to 1 of 2 additional treatment arms (arm III or IV).

ARM III: Patients receive 1 course of the same treatment that they receive in arm I or II.

ARM IV: Patients receive 1 course of the same treatment that they receive in arm I or II. 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 oral capecitabine twice daily 5 days per week or fluorouracil IV continuously for 5.5 weeks or until radiotherapy is completed.

After completion of study, patients are followed up periodically.