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

Primary Purpose

Advanced Non-Small Cell Lung Cancer

Status

Unknown status

Phase

Phase 1

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Irinotecan

Cisplatin

TS-1 (S-1)

About this trial

This is an interventional treatment trial for Advanced Non-Small Cell Lung Cancer focused on measuring Non small cell lung cancer, Irinotecan plus Cisplatin plus S-1, Phase I/II trial

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.
Metastasis of CNS is not regard to exclusion if the symptom is controlled properly for supportive care including corticosteroid.
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.

Exclusion Criteria:

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.

Sites / Locations

Asan Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

study arm

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

To estimate the time to progression and overall survival

Determine MTD (Maximum tolerated dose) in phase I

Full Information

NCT ID

NCT00874328

First Posted

December 24, 2008

Last Updated

October 22, 2010

Sponsor

National Cancer Center, Korea

Collaborators

Jeil Pharmaceutical Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT00874328

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2010

Overall Recruitment Status

Unknown status

Study Start Date

October 2008 (undefined)

Primary Completion Date

December 2011 (Anticipated)

Study Completion Date

December 2012 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor

National Cancer Center, Korea

Collaborators

Jeil Pharmaceutical Co., Ltd.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Advanced Non-Small Cell Lung Cancer

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

74 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

study arm

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Irinotecan

Other Intervention Name(s)

Campto

Intervention Description

Irinotecan iv D1 q 3 weeks until maximum 6 cycles

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

TS-1 (S-1)

Other Intervention Name(s)

S-1

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Time Frame

1 year

Secondary Outcome Measure Information:

Title

To estimate the time to progression and overall survival

Time Frame

2 years

Title

Determine MTD (Maximum tolerated dose) in phase I

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Metastasis of CNS is not regard to exclusion if the symptom is controlled properly for supportive care including corticosteroid. 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. Exclusion Criteria: 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Sung JIn Yoon, RN

Phone

+82-31-920-0405

jinijiniya@ncc.re.kr

First Name & Middle Initial & Last Name or Official Title & Degree

Tak Yun, M.D.

Phone

+82-31-920-+1621

hmotakyun@ncc.re.kr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Heung Tae Kim, M.D.

Organizational Affiliation

National Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Asan Medical Center

City

Seoul

ZIP/Postal Code

138-736

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Dae Ho Lee, M.D.

Phone

+82-2-3010-3214

leedaeho@amc.seoul.kr

12. IPD Sharing Statement

Learn more about this trial

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

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