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

NCT00874328 | Unknown Phase 1 DMC

• 1 other identifier: NCCCTS-08-333
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Non-Small Cell Lung Cancer

Keywords

Non small cell lung cancer; Irinotecan plus Cisplatin plus S-1; Phase I/II trial

Outcome Measures

Primary Outcomes (1)

• Evaluation the Response rate IP plus TS-1(in phase 2)

  1 year

Secondary Outcomes (2)

• To estimate the time to progression and overall survival

  2 years

• Determine MTD (Maximum tolerated dose) in phase I

  6 months

Study Arms (1)

study arm

EXPERIMENTAL

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

Drug: Irinotecan; Drug: Cisplatin; Drug: TS-1 (S-1)

Interventions

Irinotecan DRUG

Irinotecan iv D1 q 3 weeks until maximum 6 cycles

Also known as: Campto

study arm

Cisplatin DRUG

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

study arm

TS-1 (S-1) DRUG

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

Also known as: S-1

study arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.
• 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.)
• Performance status of 0, 1, 2 on the ECOG criteria.
• At least one uni-dimensionally measurable lesion meeting Response Evaluation Criteria in Solid Tumors (RECIST 2000).
• Estimated life expectancy of at least 12 weeks.
• Patient compliance that allows adequate follow-up.
• Adequate organ function.
• Informed consent from patient
• 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.

You may not qualify if:

• MI within preceding 6 months or symptomatic heart disease, including unstable angina, congestive heart failure or uncontrolled arrhythmia
• Serious concomitant infection including post-obstructive pneumonia
• 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)
• Pregnant or nursing women
• Psychiatric disorder that would preclude compliance.
• Major surgery other than biopsy within the past two weeks.
• Patients receiving a concomitant treatment with drugs interacting with S-1 such as flucytosine, phenytoin, or warfarin et al.

Sponsors & Collaborators

• National Cancer Center, Korea: lead
• Jeil Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Asan Medical Center

Seoul, 138-736, South Korea

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Irinotecan; Cisplatin; titanium silicide; S 1 (combination)

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Heung Tae Kim, M.D.

  National Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sung JIn Yoon, RN

CONTACT

+82-31-920-0405; jinijiniya@ncc.re.kr

Tak Yun, M.D.

CONTACT

+82-31-920-+1621; hmotakyun@ncc.re.kr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV

Study Record Dates

• First Submitted: December 24, 2008
• First Posted: April 2, 2009
• Study Start: October 1, 2008
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2012
• Last Updated: October 25, 2010

Record last verified: 2010-07

Locations

KR (1)