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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2010 by National Cancer Center, Korea.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Jeil Pharmaceutical Co., Ltd.
Information provided by:
National Cancer Center, Korea
ClinicalTrials.gov Identifier:
NCT00874328
First received: December 24, 2008
Last updated: October 22, 2010
Last verified: July 2010
  Purpose

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.


Condition Intervention Phase
Advanced Non-Small Cell Lung Cancer
Drug: Irinotecan
Drug: Cisplatin
Drug: TS-1 (S-1)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of TS-1, Irinotecan and Cisplatin for Patients With Advanced or Metastatic NSLC

Resource links provided by NLM:


Further study details as provided by National Cancer Center, Korea:

Primary Outcome Measures:
  • Evaluation the Response rate IP plus TS-1(in phase 2) [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To estimate the time to progression and overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Determine MTD (Maximum tolerated dose) in phase I [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 74
Study Start Date: October 2008
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: study arm
Irinotecan /IV D1 Cisplatin 60mg/m2 iv D1 S-1 bid, P.o. D1 ~ 14 q 3 weeks until maximum 6 cycles
Drug: Irinotecan
Irinotecan iv D1 q 3 weeks until maximum 6 cycles
Other Name: Campto
Drug: Cisplatin
cisplatin 60mg/m2 iv D1 q 3weeks until maximum 6 cycles
Other Name: Cisplatin
Drug: TS-1 (S-1)
TS-1 po D1~D14 q 3 weeks until maximum 6 cycles
Other Name: S-1

Detailed Description:

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.

  Eligibility

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

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00874328

Contacts
Contact: Sung JIn Yoon, RN +82-31-920-0405 jinijiniya@ncc.re.kr
Contact: Tak Yun, M.D. +82-31-920-+1621 hmotakyun@ncc.re.kr

Locations
Korea, Republic of
Asan Medical Center Recruiting
Seoul, Korea, Republic of, 138-736
Contact: Dae Ho Lee, M.D.    +82-2-3010-3214    leedaeho@amc.seoul.kr   
Sponsors and Collaborators
National Cancer Center, Korea
Jeil Pharmaceutical Co., Ltd.
Investigators
Principal Investigator: Heung Tae Kim, M.D. National Cancer Center
  More Information

No publications provided

Responsible Party: Heung Tae Kim, National Cancer Center, Korea
ClinicalTrials.gov Identifier: NCT00874328     History of Changes
Other Study ID Numbers: NCCCTS-08-333
Study First Received: December 24, 2008
Last Updated: October 22, 2010
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by National Cancer Center, Korea:
Non small cell lung cancer
Irinotecan plus Cisplatin plus S-1
Phase I/II trial

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Irinotecan
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 01, 2014