A PHASE III TRIAL EVALUATING BOTH ERLOTINIB AND CHEMORADIATION AS ADJUVANT TREATMENT FOR PATIENTS WITH RESECTED HEAD OF PANCREAS ADENOCARCINOMA

Trial Information

A PHASE III TRIAL EVALUATING BOTH ERLOTINIB AND CHEMORADIATION AS ADJUVANT TREATMENT FOR PATIENTS WITH RESECTED HEAD OF PANCREAS ADENOCARCINOMA

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.