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An Open-Label, Non-Randomized, Multicenter, Three-Stage, Phase 2 Study of S-1 in Combination With Cisplatin as 1st Line Therapy for Patients With Advanced Non-Small Cell Lung Cancer (Stage IIIB/Stage IV)

Phase 2
18 Years
Not Enrolling
Advanced Non-Small Cell Lung Cancer

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Trial Information

An Open-Label, Non-Randomized, Multicenter, Three-Stage, Phase 2 Study of S-1 in Combination With Cisplatin as 1st Line Therapy for Patients With Advanced Non-Small Cell Lung Cancer (Stage IIIB/Stage IV)

Advanced non-small cell lung 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.

This is an open-label, multicenter, single-arm, 3-stage, Phase 2 study evaluating the
efficacy and safety of S-1 in combination with cisplatin as 1st line therapy for patients
with advanced NSCLC. The 3 stages of this study correspond to a run-in tolerability stage
(stage 1), futility stage (stage 2), and decision stage (stage 3). The run-in tolerability
stage will be conducted to assess any additional toxicity associated with a more frequent
schedule of administration of cisplatin (75 mg/m2 every 3 weeks) compared with the dosing
regimen established in a prior Phase I study in patients with advanced gastric cancer (75
mg/m2 every 4 weeks). The futility stage (stage 2) will be conducted to ensure that this
treatment combination is sufficiently efficacious to expose a sufficient number of patients
to be able to make a decision (stage 3) on whether this combination treatment warrants
further evaluation in future studies.

Inclusion Criteria:

- 1. Has given written informed consent. 2. Patients with histologically and/or
cytologically proven unresectable NSCLC stage IIIB with pleural effusion or
pericardial effusion, or stage IV (mixed forms with small cell lung cancer are

3. Has measurable disease as defined by Response Evaluation Criteria in Solid Tumors
(RECIST) criteria, ie, has at least one measurable lesion. A measurable lesion is one
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)

4. Is able to take medications orally. 5. Is ≥ 18 years of age. 6. Has an ECOG
performance status 0 or 1. 7. Has adequate organ function as defined by the following

1. AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN; if liver function abnormalities are due
to underlying liver metastasis AST (SGOT) and ALT (SGPT) ≤ 5 x ULN.

2. Total serum bilirubin of ≤ 1.5 x ULN.

3. Absolute granulocyte count of ≥ 1,500/mm3.

4. Platelet count ≥ 100,000/mm3.

5. Hemoglobin of ≥ 9.0 g/dL.

6. Calculated creatinine clearance (CrCl) ≥ 60 mL/minute (Cockcroft-Gault formula).

8. Is willing and able to comply with scheduled visits, treatment plans,
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 cytotoxic chemotherapy except for adjuvant or neo-adjuvant therapy for
NSCLC beyond 12 months.

2. Any 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. Radiotherapy within the prior 2 weeks.

4. Adjuvant or neo-adjuvant therapy within the past 12 months.

5. Prior cisplatin as neo-adjuvant and/or adjuvant chemotherapy with cumulative
dose > 300 mg/m2.

6. Any investigational agent, either concurrently or within the past 30 days.

7. 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. Has a serious illness or medical condition(s) including, but not limited to,
the following:

1. Other active malignancies.

2. Symptomatic brain metastasis not controlled by corticosteroids.

3. Leptomeningeal metastasis.

4. Known neuropathy Grade 2 or higher.

5. Myocardial infarction within the last 6 months, severe/unstable angina,
congestive heart failure New York Heart Association (NYHA) class III or IV.

6. Chronic nausea, vomiting, and/or diarrhea.

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

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

9. 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.

3. Is receiving 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
activity).4. Is receiving concomitant treatment with drugs interacting with
cisplatin. The following drugs are prohibited because there may be an
interaction with cisplatin:

1. Phenytoin (cisplatin may diminish phenytoin activity).

2. Aminoglycosides (should be avoided within 8 days after cisplatin

5. Is a pregnant or lactating female. 6. Has known hypersensitivity to
cisplatin. 7. With reproductive potential and 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 a max of 6 cycles. Tumor assessments will 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:

February 2005

Completion Date:

July 2007

Related Keywords:

  • Advanced Non-Small Cell Lung Cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms