An Open-Label, Non-Randomized, Multicenter, Two-Stage, Phase 2 Study of S-1 in Chemotherapy-Naïve Patients With Locally Advanced or Metastatic Pancreatic Cancer
- 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.
- 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
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
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).