S-1, Gemcitabine and Erlotinib for Advanced Pancreatic Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2012 by Hallym University Medical Center
Sponsor:
Collaborator:
Jeil Pharmaceutical Co., Ltd.
Information provided by (Responsible Party):
Hallym University Medical Center
ClinicalTrials.gov Identifier:
NCT01693419
First received: September 20, 2012
Last updated: September 22, 2012
Last verified: September 2012
  Purpose

This study 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


Condition Intervention Phase
Pancreas Neoplasms
Drug: GES (Gemcitabine, Erlotinib, S-1)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of S-1 in Combination With Gemcitabine and Erlotinib in Patients With Advanced or Metastatic Pancreatic Cancer

Resource links provided by NLM:


Further study details as provided by Hallym University Medical Center:

Primary Outcome Measures:
  • Objective response rate [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression free survival [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
  • Disease control rate [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
  • Toxicity profiles [ Time Frame: 1.5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 28
Study Start Date: August 2011
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GES (Gemcitabine, Erlotinib, S-1)

Treatment will be delivered as a 3-week cycle.

  1. Gemcitabine 1000 mg/m² IV on day 1, 8
  2. Erlotinib 100 mg/day PO on day 1
  3. S-1 60 mg/m²/day PO on day 1-14
Drug: GES (Gemcitabine, Erlotinib, S-1)

Treatment will be delivered as a 3-week cycle.

  1. Gemcitabine 1000 mg/m² IV on day 1, 8
  2. Erlotinib 100 mg/day PO on day 1
  3. S-1 60 mg/m²/day PO on day 1-14
Other Names:
  • Gemzar
  • Tarceva
  • TS-1

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 chemotherapy.
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01693419

Contacts
Contact: Dae Young Zang, MD, PhD 82313803871 fhdzang@hallym.or.kr
Contact: Jin Hee Jung, RN 82313803704 jhjung23@daum.net

Locations
Korea, Republic of
Hallym University Medical Center Recruiting
Anyang, Korea, Republic of
Contact: Dae Young Zang, MD, PhD    82313803871    fhdzang@hallym.or.kr   
Contact: Jin Hee Jung, RN    82313803704    jhjung23@daum.net   
Sub-Investigator: Hyeong Su Kim, MD         
Sub-Investigator: Boram Han, MD         
Sponsors and Collaborators
Hallym University Medical Center
Jeil Pharmaceutical Co., Ltd.
Investigators
Principal Investigator: Dae Young Zang, DM, PhD Hallym University Medical Center
  More Information

No publications provided

Responsible Party: Hallym University Medical Center
ClinicalTrials.gov Identifier: NCT01693419     History of Changes
Other Study ID Numbers: HMC-HO-GI-1201
Study First Received: September 20, 2012
Last Updated: September 22, 2012
Health Authority: Korea: Food and Drug Administration

Keywords provided by Hallym University Medical Center:
pancreas neoplasm
gemcitabine
erlotinib
S-1

Additional relevant MeSH terms:
Neoplasms
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Erlotinib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014