Phase 2 Study of S-1 in Combination With Cisplatin as 1st Line Therapy in Advanced Non-Small Cell Lung Cancer - Full Text View

Sponsors and Collaborators:	Taiho Pharma USA, Inc. Quintiles United Biosource Corporation
Information provided by:	Taiho Pharma USA, Inc.
ClinicalTrials.gov Identifier:	NCT00651833

Purpose

The purpose of this study is to determine whether S-1 in combination with Cisplatin is effective as 1st line therapy in slowing tumor activity in patients with advanced non-small cell lung cancer. The study is also looking at the safety of S-1.

Condition	Intervention	Phase
Advanced Non-Small Cell Lung Cancer	Drug: S-1	Phase II

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Cisplatin S 1 (Combination)

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Efficacy Study
Official Title:	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)

Further study details as provided by Taiho Pharma USA, Inc.:

Primary Outcome Measures:

Overall tumor response rate (ORR - the proportion of patients with objective evidence of PR or CR) [ 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. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To evaluate the safety profile of S-1 [ Time Frame: AEs will be reported through follow-up (30 days after the last dose of study medication); blood/urine will be collected at baseline ; Days 8 and 15; w/in 24 hrs prior to study drug on Day 1 of each cycle after Cycle 1; at the end of study treatment. ] [ Designated as safety issue: Yes ]
To evaluate the duration of response (DR), and progression-free survival (PFS) [ Time Frame: Each cycle will last 21 days (14 days treatment, 7 days recovery) for a max of 6 cycles. Following discont'n of treatment , pts will be followed for survival status every 2 mos following PD for up to 6 mos. ] [ Designated as safety issue: No ]
To investigate the relationship of S-1 plasma levels (components and metabolites) with safety and efficacy parameters [ Time Frame: Each cycle will last 21 days (14 days treatment, 7 days recovery) for a max of 6 cycles. Blood samples to be obtained 1.5 ± 0.5 h, 5 ± 1 h, 7 ± 1 h postdose on Day 1 of Cycle 1 only. ] [ Designated as safety issue: Yes ]

Enrollment:	60
Study Start Date:	February 2005
Study Completion Date:	July 2007
Primary Completion Date:	July 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental All patients will receive S-1 orally at a dose of 25 mg/m2 twice daily (BID) for 14 days followed by a 1-week recovery period, repeated every 3 weeks. Patient will also receive cisplatin, 75 mg/m2 as a 1- to 3-hour infusion on Day 1 of each cycle.	Drug: S-1 All patients will receive S-1 orally at a dose of 25 mg/m2 twice daily (BID) for 14 days followed by a 1-week recovery period, repeated every 3 weeks. The study may go to the third stage only if 7/31 (23%) or more patients have achieved a confirmed response (CR or PR) in stages 1 and 2 combined.

Detailed Description:

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.

Eligibility

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

Criteria

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 excluded). 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) scan. 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 criteria:
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 disease).
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 activity).
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 administration).
  
  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).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00651833

Sponsors and Collaborators

Taiho Pharma USA, Inc.

Quintiles

United Biosource Corporation

Investigators

Study Director:

Peter Urrea, PhD

Taiho Pharma USA, Inc.

More Information

No publications provided

Responsible Party:	Taiho Pharma USA, Inc. ( Peter Urrea/Senior VP, Clinical and Regulatory Affairs )
Study ID Numbers:	TPU-S1202
Study First Received:	March 31, 2008
Last Updated:	March 31, 2008
ClinicalTrials.gov Identifier:	NCT00651833 History of Changes
Health Authority:	United States: Food and Drug Administration

Study placed in the following topic categories:

Thoracic Neoplasms
Cisplatin
Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases

Non-small Cell Lung Cancer
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:

Thoracic Neoplasms
Respiratory Tract Neoplasms
Neoplasms
Neoplasms by Site
Neoplasms by Histologic Type
Respiratory Tract Diseases

Lung Neoplasms
Lung Diseases
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Carcinoma

ClinicalTrials.gov processed this record on May 07, 2009