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An Open-Label, Non-Randomized, Multicenter, Two-Stage, Phase 2 Study of S-1 as 2nd Line Therapy for Patients With Metastatic Pancreatic Cancer Who Have Previously Received 1st Line Treatment With a Gemcitabine Regimen

Phase 2
18 Years
Not Enrolling
Secondary Malignant Neoplasm of Pancreas

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Trial Information

An Open-Label, Non-Randomized, Multicenter, Two-Stage, Phase 2 Study of S-1 as 2nd Line Therapy for Patients With Metastatic Pancreatic Cancer Who Have Previously Received 1st Line Treatment With a Gemcitabine Regimen

Metastatic pancreatic cancer is relatively unresponsive to chemotherapy. This is true for
the nucleoside analogue gemcitabine, with a response rate of approximately 10%, as well as
for 5-fluorouracil (5-FU). Even when gemcitabine is combined with other chemotherapeutic
drugs or biological agents, the overall tumor response rate remains basically unchanged.
S-1 is a new generation oral fluoropyrimidine that combines Tegafur
(5-fluoro-1-(tetrahydro-2-furanyl)-2,4(1H,3H)-pyrimidinedione [FT]), an oral prodrug of
5-FU, with two modulators, Gimeracil (5-chloro-2,4-dihydroxypyridine [CDHP]), which inhibits
5-FU degradation by dihydropyrimidine dehydrogenase (DPD) inhibition, and Oteracil potassium
(Oxo), which inhibits 5-FU phosphorylation in the digestive tract. This combination of 3
compounds is designed to achieve enhanced antitumor activity while decreasing
gastrointestinal toxicity.

Inclusion Criteria:

- 1. Has provided written informed consent. 2. Has histologically or cytologically
confirmed locally advanced, unresectable or metastatic adenocarcinoma of the pancreas
not amenable to curative radiotherapy or surgery.

3. Has measurable disease as defined by Response Evaluation Criteria in Solid Tumors
(RECIST) criteria (ie, lesions that can be accurately measured in at least one
dimension with the longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm
using spiral computed tomography [CT] scan).

4. Is able to take medications orally. 5. Is 18 years of age or older. 6. Has a
Karnofsky Performance Status (KPS) ≥ 70% (see Appendix A). 7. Has a life expectancy
of ≥ 12 weeks. 8. Has adequate organ function as defined by the following criteria:

1. Transaminases AST (SGOT) and ALT (SGPT) ≤ 2.5 times the upper limit of normal
(ULN). If liver function abnormalities are due to underlying liver metastasis,
then AST (SGOT) and ALT (SGPT) may be ≤ 5 times ULN.

2. Total serum bilirubin ≤ 3.0 times ULN (if due to underlying liver metastasis,
then total bilirubin may be ≤ 5 times ULN).

3. Absolute granulocyte count ≥ 1,500/mm3 (ie, ≥ 1.5 x 109/L by International Units

4. Platelet count ≥ 100,000/mm3 (IU: ≥ 100 x 109/L).

5. Hemoglobin value ≥ 9.0 g/dL.

6. Calculated creatinine clearance ≥ 60 mL/min (based on serum creatinine)
(Cockcroft-Gault85 formula) 9. Is willing and able to comply with scheduled
visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

- 1. Has had treatment with any of the following within the specified time frame prior
to study drug administration:

1. Any prior anticancer chemotherapy.

2. Radiation therapy to a target lesion unless there was evidence of PD after
radiotherapy (and this target lesion must not be the only site of measurable

3. Any radiotherapy within the previous 3 weeks.

4. Any investigational agent received either concurrently or within the last 30

5. Current enrollment in another clinical study with an investigational agent.
Patients participating in surveys or observational studies are eligible to
participate in this study.

2. Major surgery within the previous 3 weeks. 3. Symptomatic brain metastasis
not controlled by corticosteroids. 4. Leptomeningeal metastasis. 5. Previous or
concurrent malignancy other than pancreatic cancer except adequately treated
carcinoma in-situ of the cervix or non-melanoma skin cancer. 6. Uncontrolled
ascites requiring drainage at least twice a week. 7. Other serious illness or
medical condition(s) including, but not limited to, the following:

1. Uncontrolled congestive heart failure (New York Heart Association [NYHA] Class
III or IV), angina pectoris, arrhythmias, or hypertension.

2. Active infection.

3. Known (at time of entry) gastrointestinal disorder, including malabsorption,
chronic nausea, vomiting, or diarrhea, present to the extent that it might
interfere with oral intake and absorption of study medication.

4. Poorly controlled diabetes mellitus.

5. Psychiatric disorder that may interfere with consent and/or protocol compliance.

6. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
(AIDS)-related illness.

7. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or
study drug administration, or may interfere with the interpretation of study
results, and in the judgment of the Investigator would make the patient
inappropriate for entry into this study.

8. Is receiving a concomitant treatment with drugs interacting with S-1. The
following drugs are prohibited because there may be an interaction with S-1:

1. Sorivudine, uracil, cimetidine, folinic acid, and dipyridamole (may enhance S-1

2. Allopurinol (may diminish S-1 activity).

3. Phenytoin (S-1 may enhance phenytoin activity).

4. Flucytosine, a fluorinated pyrimidine antifungal agent (may enhance S-1 and
flucytosine activity).

9. Is a pregnant or lactating female. 10. Has known sensitivity to 5-FU. 11. Is
a patient with reproductive potential who refuses to use an adequate means of
contraception (including male patients).

Type of Study:


Study Design:

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

Outcome Measure:

Overall tumor response rate (ORR - the proportion of patients with objective evidence of PR or CR)

Outcome Time Frame:

Each cycle will last 21 days (14 days treatment, 7 days recovery) for 6 mos. Tumor assessmentswill be obtained at baseline) and at the end of every even cycle.

Safety Issue:


Principal Investigator

Fabio Benedetti, MD

Investigator Role:

Study Director

Investigator Affiliation:

Taiho Pharma USA, Inc.


United States: Food and Drug Administration

Study ID:




Start Date:

June 2005

Completion Date:

October 2007

Related Keywords:

  • Secondary Malignant Neoplasm of Pancreas
  • Neoplasms
  • Pancreatic Neoplasms
  • Neoplasms, Second Primary