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A Phase II Study of S-1 in Combination With Gemcitabine and Erlotinib in Patients With Advanced or Metastatic Pancreatic Cancer

Phase 2
18 Years
Open (Enrolling)
Pancreas Neoplasms

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Trial Information

A Phase II Study of S-1 in Combination With Gemcitabine and Erlotinib in Patients With Advanced or Metastatic Pancreatic Cancer

Pancreatic ductal adenocarcinoma, also known as pancreatic cancer, is an eighth cause of
cancer-related deaths in the world. The estimated worldwide incidence of pancreatic cancer
was 277,000 cases and an estimated 266,000 patients died from the disease in 20081.

Pancreatic cancer is more common in elderly persons than in younger persons, and
characterised by early locoregional spread and distant metastasis. As a result, less than
20% of patients are diagnosed with localized, potentially curable disease, and the median
survival is no longer than 3-4 months without effective treatment2.

Single-agent chemotherapy with gemcitabine was considered as standard of care for patients
with advanced pancreatic cancer, since Burris et al. demonstrated superiority of gemcitabine
over 5-fluorouracil (5-FU) in respect of a survival benefit as well as an improvement in
disease related symptoms in a randomized study3.

Nevertheless, the activity of gemcitabine monotherapy in pancreatic cancer was modest, and
there was a clear need to improve its efficacy by combining it with other anticancer drugs.

Multiple agents such as 5-FU4, capecitabine5,6, cisplatin7,8, oxaliplatin9, pemetrexed10,
irinotecan11, cetuximab12, and bevacizumab13, in combination with gemcitabine have been
tested in clinical trials, however, they have failed to improve the outcome.

The only agent that, in combination with gemcitabine, has shown a small, but statistically
significant improvement, with a hazard ratio (HR) of 0.82, the absolute improvement in
median overall survival (OS) of 5.9 months with gemcitabine versus 6.2 months with the
combination, is erlotinib, a small-molecule inhibitor of the epidermal growth factor
receptor (EGFR)14. Considering the modest improvement in survival by adding erlotinib to
gemcitabine, new combination therapy that have a great impact is urgently needed.

S-1 is an oral fluoropyrimidine derivative that combines tegafur (FT) with two modulators;
5-chloro-2, 4-dihydroxypyridine (CDHP) and oteracil potassium (Oxo) in a 1:0.4:1 molar
concentration ratio. The phase II trials of a combination of gemcitabine and S-1 have
demonstrated objective response rates of 32-48% and median survival of 8-12 months 15-17.

Therefore, we will conduct a phase II study of gemcitabine, erlotinib, and S-1 as first-line
chemotherapy in patients with advanced pancreatic cancer and evaluate the EGFR expression,
KRAS mutation, and BRAF mutation as predictive or prognostic markers.

Inclusion Criteria:

- Pathologically confirmed locally advanced unresectable, recurrent or metastatic
adenocarcinoma of pancreas (Stage III-IV ; TNM staging system)

- Measurable or evaluable disease by RECIST criteria 1.1

- Minimum age of 18 years

- ECOG Performance status 0-1

- Prior adjuvant chemotherapy without gemcitabine, erlotinib or S-1 is allowed if more
than 4 weeks elapsed since completion of chemotherapy.

- More than 4 weeks since completion of prior radiotherapy (measurable or evaluable
lesions should be outside the radiation field)

- Adequate organ functions

- Patients must sign an informed consent indicating that they are aware of the
investigational nature of the study in keeping with the policy of the hospital.

Exclusion Criteria:

- Patients treated previously with gemcitabine, erlotinib, or S-1 as adjuvant

- Patients with CNS metastases

- Patients with active infection, severe heart disease, uncontrollable hypertension or
diabetes mellitus, myocardial infarction during the preceding 6 months, pregnancy, or
breast feeding

- Any previous or concurrent malignancy other than non-melanoma skin cancer or in situ
cancer of uterine cervix

- Known history of cerebral or leptomeningeal metastases or neurologic disease

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective response rate

Outcome Time Frame:

1.5 years

Safety Issue:


Principal Investigator

Dae Young Zang, DM, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Hallym University Medical Center


Korea: Food and Drug Administration

Study ID:




Start Date:

August 2011

Completion Date:

December 2012

Related Keywords:

  • Pancreas Neoplasms
  • pancreas neoplasm
  • gemcitabine
  • erlotinib
  • S-1
  • Neoplasms
  • Pancreatic Neoplasms