A Study of TS-1 Plus Irinotecan and Cisplatin (IP) for Patients With Stage IIIB/IV Non Small Cell Lung Cancer (NSCLC)

NCT ID: NCT00874328

Last Updated: 2010-10-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

74 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-10-31

Study Completion Date

2012-12-31

Brief Summary

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The irinotecan and cisplatin combination showed significant anti-tumor activity. In the first-line setting, the investigators showed that this regimen had significant anti-tumor activity in 47% of chemo-naïve NSCLC patients with 1-year survival rate of 64.2%. Again, the investigators showed that the second-line Irinotecan and cisplatin is an active and well-tolerated regimen in patients with advanced NSCLC pretreated with non-platinum based chemotherapy.

TS-1 (Jeil Pharmaceutical Co.,Ltd, Seoul, Korea) is an oral anticancer drug comprised of tegafur, 5-chloro-2, 4-dihydroxypyridine and potassium oxonate, in a molar ratio of 1:0.4:1. Tegafur is a prodrug that generates 5-fluorouracil (5-FU) in blood via metabolism by liver enzyme, and 5-chloro-2, 4-dihydroxypyridine enhance the serum concentration of 5-FU by the competitive inhibition of dihydropyrimidine dehydrogenase, an enzyme responsible for 5-FU catabolism. Potassium oxonate is also a reversible competitive inhibitor of orotate phosphoribosyl transferase, a phosphoenzyme for 5-FU. Diarrhea induced by 5-FU administration is though to be attributable to the phosphorylation of 5-FU by the enzyme in the gastrointestinal tissue. After oral administration of potassium oxonate, the concentration of potassium in the gastrointestinal tissue is high enough to inhibit the enzyme while the concentration in blood and tumor is reported to be either slight or nil. Because of these mechanism, oral TS-1 administration generates a higher concentration of 5-FU than protracted intravenous infusion of 5-FU given in a dose equimolar to the tegafur in S-1, whereas the incidence of adverse events concerning the GI tract does not increase. In a phase II trial of TS-1 as first-line setting in NSCLC, the response rate was 22% and the median survival time was 10.2 months. As expected, the incidence of severe gastrointestinal adverse events was low, and so was few severe hematologic toxicity. Recently 3-weekly TS-1 plus cisplatin showed activity against NSCLC with a response rate of 32.7% and the safety was acceptable.

Detailed Description

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The investigators are conducting a phase I/II study to determine the maximum-tolerated dose, the recommended dose, and to evaluate the response rate and toxicity of the TS-1, irinotecan and cisplatin combination in patients with advanced or metastatic NSCLC.

Conditions

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Advanced Non-Small Cell Lung Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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study arm

Irinotecan /IV D1 Cisplatin 60mg/m2 iv D1 S-1 bid, P.o. D1 \~ 14 q 3 weeks until maximum 6 cycles

Group Type EXPERIMENTAL

Irinotecan

Intervention Type DRUG

Irinotecan iv D1 q 3 weeks until maximum 6 cycles

Cisplatin

Intervention Type DRUG

cisplatin 60mg/m2 iv D1 q 3weeks until maximum 6 cycles

TS-1 (S-1)

Intervention Type DRUG

TS-1 po D1\~D14 q 3 weeks until maximum 6 cycles

Interventions

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Irinotecan

Irinotecan iv D1 q 3 weeks until maximum 6 cycles

Intervention Type DRUG

Cisplatin

cisplatin 60mg/m2 iv D1 q 3weeks until maximum 6 cycles

Intervention Type DRUG

TS-1 (S-1)

TS-1 po D1\~D14 q 3 weeks until maximum 6 cycles

Intervention Type DRUG

Other Intervention Names

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Campto S-1

Eligibility Criteria

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Inclusion Criteria

1. Histologic or cytologic diagnosis of NSCLC, Stage IV or selected stage IIIB (with malignant pleural or pericardial effusion) according to the American Joint Committee on Cancer (AJCC).
2. In phase I, previous chemotherapy including cytotoxic chemotherapy except for irinotecan and cisplatin therapy, targeted therapy and/or radiotherapy is allowed; patients are required to have discontinued previous anti-tumor treatment for at least 4 weeks. Neoadjuvant chemotherapy or adjuvant chemotherapy is allowed and regarded as one-time systemic chemotherapy.
3. In phase II, no prior chemotherapy, radiotherapy or target therapy is allowed. (Prior radiation therapy is allowed as long as the irradiated area is not the only source of measurable disease. Neoadjuvant chemotherapy or adjuvant chemotherapy is not allowed.)
4. Performance status of 0, 1, 2 on the ECOG criteria.
5. At least one uni-dimensionally measurable lesion meeting Response Evaluation Criteria in Solid Tumors (RECIST 2000).
6. Estimated life expectancy of at least 12 weeks.
7. Patient compliance that allows adequate follow-up.
8. Adequate organ function.
9. Metastasis of CNS is not regard to exclusion if the symptom is controlled properly for supportive care including corticosteroid.
10. Informed consent from patient
11. If female: childbearing potential either terminated by surgery, radiation, or menopause, or attenuated by use of an approved contraceptive method (intrauterine device \[IUD\], birth control pills, or barrier device) during and for 3 months after trial. If male, use of an approved contraceptive method during the study and 3 months afterwards. Females with childbearing potential must have a urine negative hCG test within 7 days prior to the study treatment.

Exclusion Criteria

1. MI within preceding 6 months or symptomatic heart disease, including unstable angina, congestive heart failure or uncontrolled arrhythmia
2. Serious concomitant infection including post-obstructive pneumonia
3. Second primary malignancy (except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin or prior malignancy treated more than 5 years from the diagnosis without recurrence)
4. Pregnant or nursing women
5. Psychiatric disorder that would preclude compliance.
6. Major surgery other than biopsy within the past two weeks.
7. Patients receiving a concomitant treatment with drugs interacting with S-1 such as flucytosine, phenytoin, or warfarin et al.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Jeil Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role collaborator

National Cancer Center, Korea

OTHER_GOV

Sponsor Role lead

Responsible Party

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National Cancer Center, Korea

Principal Investigators

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Heung Tae Kim, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Center

Locations

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Asan Medical Center

Seoul, , South Korea

Site Status RECRUITING

Countries

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South Korea

Central Contacts

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Sung JIn Yoon, RN

Role: CONTACT

+82-31-920-0405

Tak Yun, M.D.

Role: CONTACT

+82-31-920-+1621

Facility Contacts

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Dae Ho Lee, M.D.

Role: primary

+82-2-3010-3214

Other Identifiers

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NCCCTS-08-333

Identifier Type: -

Identifier Source: org_study_id