Irinotecan Plus Cisplatin Compared With Etoposide Plus Cisplatin for Extensive Stage Small-cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
This study is aimed to evaluate the progression-free survival(PFS) and also survival of IP and EP (head-to-head) as the first line therapy for extensive stage small-cell lung cancer and to explore the reasonable first-line therapy for Chinese population. An open-label, multi-center study will be conducted with dynamic randomization of approximately 1:1 ratio with an estimation of 308 eligible participants.

Detailed Description
-----------------
evaluate the progression-free survival(PFS) and also survival of IP and EP (head-to-head) as the first line therapy for extensive stage small-cell lung cancer and to explore the reasonable first-line therapy for Chinese population. An open-label, multi-center study will be conducted with dynamic randomization of approximately 1:1 ratio with an estimation of 308 eligible participants.

Official Title
-----------------
Irinotecan Plus Cisplatin Compared With Etoposide Plus Cisplatin for Extensive Stage Small-cell Lung Cancer: a Multi-center, Randomized, Open Label Study

Conditions
-----------------
Small Cell Lung Cancer

Intervention / Treatment
-----------------
* Drug: Irinotecan
* Drug: Etoposide
* Drug: Cisplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Cytologically or histologically confirmed extensive stage small-cell lung cancer (remote metastasis and/or contralateral lymph-node involvement; not those with simple ipsilateral pleural effusion); No prior radiotherapy, chemotherapy or surgery; At least one measurable lesion, CT≥20mm, spiral CT≥10mm(diameter); ECOG PS 0-1; Age 18-70; Life expectancy > three months; In general normal function of heart, liver, kidney and bone marrow; WBC C>4.0×10(9)/L, NEUT>1.50×10(9)/L, PLT>100×10(9)/L, Hb>95g/L; Liver function: TBIL < 1.5 x UL normal range; ALT and AST < 1.5 x UL normal range; Kidney function: normal serum creatinine level; Signed an informed consent and will comply with the study protocol and follow-up plans. Exclusion Criteria: Failed to meet the entry criteria of pathology and clinical stage; Have received prior chemotherapy or target treatment; Currently receiving other anticancer therapy; No measurable lesions or lesions cannot be assessed; Patients with acute or chronic medical or psychiatric condition, or laboratory abnormalities that may impact the judgment of the investigator and the result of the study, determined by investigator they may include: Uncontrolled tumor metastasis in central nerve system; Uncontrolled hypertension, unstable angina, MI history, or congestive heart-failure, uncontrolled arrhythmia, ischemic vascular disease within the 12 months prior to study treatment; Myocardial ischemia by ECG or valvular heart disease; Grade 3 or above peripheral neuropathy; Active stage of infection by bacteria, fungi or virus; Pregnant or breast feeding woman; History of uncontrolled mental disease. Not able to discontinue NSAIDs treatment; Other active malignant tumors except non-melanoma skin cancer, in-situ cervical carcinoma and cured early prostatic carcinoma; Patients with allergies, known or may be allergic to drugs in research; Patients with poor compliance to treatment and follow-up; Patients with UGT1A1-6 and UGT1A1-28 gene mutation; With clinical symptoms of brain metastasis(patient with stable clinical performance and no need to treat can be included in the trial); Chest, abdominal or pericardial effusion that needs anti-cancer intervention; Accompanied with Grade ≥2 diarrhea; Participated in other clinical trials within one month before randomization; Investigator's judgment to exclude.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Irinotecan plus Cisplatin<br>first line: irinotecan 65mg/m2 d1,8. Cisplatin 30mg/m2，d1,8, 21days/cycle×6 cycles Second-line: etoposide alone OR etoposide plus cisplatin, dosage will be same as first line or on investigator's discretion. | Drug: Irinotecan<br>* 40mg<br>* Other names: Ai Li;Drug: Cisplatin<br>* 6ml：30mg<br>* Other names: Nuo Xin;|
| Experimental: Etoposide plus Cisplatin<br>first line: etoposide 60mg/m2 d1-5 Cisplatin 75mg/m2，d1(recommended), or administer three times with same total daily dose , 21days/cycle×6 cycles Second-line: irinotecan alone or irinotecan plus cisplatin, dosage is same as first line or on investigator's discretion. | Drug: Etoposide<br>* 5ml：0.1g<br>* Other names: H32025583;Drug: Cisplatin<br>* 6ml：30mg<br>* Other names: Nuo Xin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival of first line therapy |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 36 months | 
| Objective Response Rate |  | 24 months | 
| Number of patients experience adverse events |  | 36 months | 
| Progression free survival of second line therapy |  | 24 months |