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

Advanced Non-Small Cell Lung Cancer Clinical Trial

Official title:

A Phase I/II Study of TS-1, Irinotecan and Cisplatin for Patients With Advanced or Metastatic NSLC

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00874328
• Other study ID #: NCCCTS-08-333
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: December 24, 2008
• Last updated: October 22, 2010
• Start date: October 2008
• Est. completion date: December 2012

Study information

• Verified date: July 2010
• Source: National Cancer Center, Korea
• Contact: Sung JIn Yoon, RN
• Phone: +82-31-920-0405
• Email: jinijiniya[@]ncc.re.kr
• Is FDA regulated: No
• Health authority: South Korea: Korea Food and Drug Administration (KFDA)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 74
• Est. completion date: December 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• Irinotecan
Irinotecan iv D1 q 3 weeks until maximum 6 cycles
• Cisplatin
cisplatin 60mg/m2 iv D1 q 3weeks until maximum 6 cycles
• TS-1 (S-1)
TS-1 po D1~D14 q 3 weeks until maximum 6 cycles

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Center, Korea	Jeil Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation the Response rate IP plus TS-1(in phase 2)		1 year	No
Secondary	To estimate the time to progression and overall survival		2 years	No
Secondary	Determine MTD (Maximum tolerated dose) in phase I		6 months	Yes