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CTRI Number  CTRI/2016/12/007605 [Registered on: 22/12/2016] Trial Registered Prospectively
Last Modified On: 03/02/2020
Post Graduate Thesis  Yes 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   study to compare effectiveness and safety of two regimes in advanced stage non small cell lung cancer. 
Scientific Title of Study   A Phase III Open label Randomized control study to compare efficacy and safety of Pemetrexed-Carboplatin versus Paclitaxel-Carboplatin as induction regimen in advanced Non-squamous Non-Small-Cell lung cancer 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  DR PRABHAT SINGH MALIK 
Designation  ASSITANT PROFESSOR 
Affiliation  DR. BRAIRCH, AIIMS 
Address  ROOM NO 245, 2ND FLOOR, DR B. R. AMBEDKAR INSTITUTE ROTARY CANCER HOSPITAL, AIIMS, ANSARI NAGAR, NEW DELHI

New Delhi
DELHI
110029
India 
Phone  9968325318  
Fax    
Email  drprabhatsm@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  DR AJAY YADAV 
Designation  SENIOR RESIDENT(DM STUDENT) 
Affiliation  DR. BRAIRCH, AIIMS 
Address  ROOM NO 245, 2ND FLOOR, DR B. R. AMBEDKAR INSTITUTE ROTARY CANCER HOSPITAL, AIIMS, ANSARI NAGAR, NEW DELHI

New Delhi
DELHI
110029
India 
Phone  8826914083  
Fax    
Email  ajayalwar01@gmail.com  
 
Details of Contact Person
Public Query
 
Name  DR PRABHAT SINGH MALIK 
Designation  ASSITANT PROFESSOR 
Affiliation  DR. BRAIRCH, AIIMS 
Address  ROOM NO 245, 2ND FLOOR, DR B. R. AMBEDKAR INSTITUTE ROTARY CANCER HOSPITAL, AIIMS, ANSARI NAGAR, NEW DELHI


DELHI
110029
India 
Phone  9968325318  
Fax    
Email  drprabhatsm@gmail.com  
 
Source of Monetary or Material Support  
All INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI 
 
Primary Sponsor  
Name  All INDIA INSTITUTE OF MEDICAL SCIENCES NEW DELHI 
Address  All INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI ANSARI NAGAR,NEW DELHI 
Type of Sponsor  Research institution and hospital 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
DR PRABHAT SINGH MALIK  ALL INDIA INSTITUTE OF MEDICAL SCIENCES NEW DELHI  DEPARTMENT OF MEDICAL ONCOLOGY, DR. BR AMBEDKER INSTITUTE ROTARY CANCER HOSPITAL
New Delhi
DELHI 
9968325318

drprabhatsm@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
INSTITUTE ETHICS COMMITTEE FOR POST GRADUATE RESEARCH, AIIMS, NEW DELHI  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied
Modification(s)  
Health Type  Condition 
Patients  ADVANCED STAGE NON SQUAMOUS NON SMALL CELL LUNG CANCER, (1) ICD-10 Condition: C349||Malignant neoplasm of unspecifiedpart of bronchus or lung,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Paclitaxel WITH Carboplatin   Paclitaxel 80 mg/m2 in 250 ml normal saline i.v. over 1 hour on Day-1, Day-8 and Day 15 – Carboplatin AUC-5 in 5% dexrose i.v. over 2 hour on Day-1 of 28 days cycle, total 4 cycles 
Intervention  Pemetrexed WITH Carboplatin   Pemetrexed (500 mg/m2) in 100 ml normal saline i.v. over 10 minute on day 1 of 21 days cycle Carboplatin at dose of (AUC -5) in 5 % dexrose i.v. over 2 hour on day 1 of 21 days cycle induction therapy include - 4 cycles at 3 week interval (Folate and vit-B12 supplementation with each cycle of chemotherapy) 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  65.00 Year(s)
Gender  Both 
Details  -Age 18-65 years
• Tissue diagnosis of Non-squamous Non-small cell lung cancer
• Stage IIIB (not amenable for radical CTRT) and stage IV
• Performance status ECOG 0, 1 and 2
• Normal renal and hepatic functions
– Creatinine clearance >50ml/min
– SGOT and SGPT < 2.5times of ULN 
 
ExclusionCriteria 
Details  • Patients who have received prior chemotherapy
• Already known EGFR/ALK mutation, if being considered for TKI
• Symptomatic brain metastasis (Asymptomatic brain metastasis and stabilized brain
metastasis after WBRT would be considered)
• Immunosuppression (HIV, or other immunosuppressant medication)
• Symptomatic neuropathy 
 
Method of Generating Random Sequence   Stratified block randomization 
Method of Concealment   Not Applicable 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
To compare Progression Free Survival in both arms  AFTER FOUR CYLES OF INDUCTION CHEMOTHERAPY 
 
Secondary Outcome  
Outcome  TimePoints 
1.To compare overall response rate in both arms
2. To compare toxicity profile in both arms
3. To compare Overall Survival in both arms
4. To compare disease control rate (CR/PR/SD) between the two induction treatment arms
5. To assess role of TS level and FRA level as predictive biomarker 
AT THE END OF THE INDUCTION CHEMOTHERAPY 
 
Target Sample Size   Total Sample Size="200"
Sample Size from India="200" 
Final Enrollment numbers achieved (Total)= "180"
Final Enrollment numbers achieved (India)="180" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   26/12/2016 
Date of Study Completion (India) 31/01/2019 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="2"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details
Modification(s)  
Pemetrexed-Carboplatin Versus Paclitaxel (Weekly)-Carboplatin as First Line Chemotherapy in Advanced Non-Squamous NSCLC Malik P, Yadav A, Jain D et al. J Thorac Oncol. 2019;14(10 S): S354-357. 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary   Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC), accounts for about 85% of all lung cancers. Platinum base chemotherapy is the standard first-line treatment for patients of advanced NSCLC who are negative for the EGFR mutation and ALK rearrangement. There are
various Cisplatin and Carboplatin based regimen approved for treatment of this group. To know which regimen is better Schiller et al, conducted a randomized clinical trial. In this trial they compared the efficacy of four doublet regimens Cisplatin plus gemcitabine, cisplatin plus docetaxel, carboplatin plus paclitaxel, or cisplatin plus paclitaxel in patients with advanced non–small-cell lung cancer. None of four chemotherapy regimens offered a significant advantage over the others. In a phase III study Scagliotti et al. found that pemetrexed plus cisplatin was noninferior to gemcitabine plus cisplatin in unselected patients with advanced-stage NSCLC. On subgroup analysis survival was significantly superior for patients with non-squamous histology who were treated with pemetrexed plus cisplatin. In phase III RCT (Point Break trial) Patel et al. compared the efficacy and safety of pemetrexed plus carboplatin plus bevacizumab followed by pemetrexed plus bevacizumab with paclitaxel plus carboplatin plus bevacizumab followed by bevacizumab in patients with advanced nonsquamous non–small-cell lung cancer. There was no difference in overall survival but PFS was significantly improved with PemCBev.  There is no trial that has compared efficacy and safety of Paclitaxel-Carboplatin versus Pemetrexed-Carboplatin. In current study we will compare the efficacy and safety of Pemetrexed-Carboplatin versus Paclitaxel-Carboplatin as induction regimen in advanced Non-squamous Non-Small-Cell lung cancer. We hypothesized that in advanced non-squamous NSCLC, four cycles of induction chemotherapy with pemetrexed and carboplatin is superior to 4 cycles of paclitaxel and carboplatin in terms of progression free survival. Several clinical trials have shown that maintenance chemotherapy is beneficial in non squamous NSCLC. Several recent studies reported that low TYMS expression was associated with better response and/or survival when treated with pemtrexed-based regimens in NSCLC patients. But some other studies did not show the significant association between TYMS expression and efficacy of pemtredxed-based chemotherapy in NSCLC. Folate receptor alpha is a glycosyl phosphatidyl inositol (GPI) anchored cell surface protein that assists in uptake of antifolates via receptor-mediated endocytosis. Some studies reported that High FRA expression associated with better response to pemetrexe. In our study we will also assess role of TS level and FRA level as predictive biomarker.


 
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