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CTRI Number  CTRI/2010/091/001245 [Registered on: 13/10/2010]
Last Modified On: 17/04/2013
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study
Modification(s)  		 Biological 
Study Design  Randomized, Parallel Group, Placebo Controlled Trial 
Public Title of Study
Modification(s)  		 A clinical trial to study the effects of IMC-1121B and best supportive care (BSC) versus Placebo and BSC in patients with metastatic gastric or gastroesophageal junction adenocarcinoma following disease progression on first line care. 
Scientific Title of Study
Modification(s)  		 A Phase 3, Randomized, Double-Blinded Study of IMC-1121B and Best Supportive Care (BSC) Versus Placebo and BSC in the Treatmentof Metastatic Gastric or Gastroesophageal Junction AdenocarcinomaFollowing Disease Progression on First-Line Platinum- or Fluoropyrimidine-Containing Combination Therapy  
Trial Acronym   
Secondary IDs if Any
Modification(s)  
Secondary ID  Identifier 
2008-005964-15  EudraCT 
CP12-0715   Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)  
Name   
Designation   
Affiliation   
Address 




 
Phone    
Fax    
Email    
 
Details of Contact Person
Scientific Query
Modification(s)  
Name  Dr Sangha Mitra Patnaik  
Designation   
Affiliation   
Address  Quintiles Research (India) Private Limited
B 101-106, Shapath IV, S G Road,
Ahmadabad
GUJARAT
380051
India 
Phone  07966303340  
Fax  07966527272  
Email  sanghamitra.patnaik@quintiles.com  
 
Details of Contact Person
Public Query
Modification(s)  
Name  Suneela Thatte 
Designation   
Affiliation   
Address  Quintiles Research (India) Pvt. Ltd.
301-A-1, Leela Business Park, 3rd Floor,M.V. Road, Andheri East,
Mumbai
MAHARASHTRA
400 059
India 
Phone  02266774263  
Fax  02266774242  
Email  Suneela.thatte@quintiles.com  
 
Source of Monetary or Material Support
Modification(s)  
ImClone LLC, 33 ImClone Drive, Branchburg, NJ 08876, USA 
 
Primary Sponsor
Modification(s)  
Name  ImClone LLC 
Address  33 ImClone Drive, Branchburg, NJ 08876, USA 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor
Modification(s)  
Name  Address 
PAREXEL International Clinical Research Private Limited  PAREXEL International Clinical Research Private Limited. Plot # 180, 3rd Floor, MFAR Silverline Tech Park, EPIP II Phase, Whitefield, Bangalore – 560066, Karnataka, India. Responsibility: Processing of all regulatory submissions to DCGI acting as applicant on behalf of the sponsor ImClone LLC"  
 
Countries of Recruitment
Modification(s)  		   India
Indonesia
Argentina
Australia
Bosnia and Herzegovina
Brazil
Canada
Chile
Croatia
Czech Republic
Democratic People's Republic of Korea
Egypt
Guatemala
Italy
Lebanon
Malta
New Zealand
Philippines
Poland
Romania
Russian Federation
South Africa
Spain
Taiwan
Thailand
Turkey
United Kingdom
United States of America  
Sites of Study
Modification(s)  
No of Sites = 12  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Madhuchanda Kar  Apollo Gleneagles Hospitals Ltd.  58, Canal Circular Road Kolkata- 700054 West Bengal

 		 03323203040
03323201739
madhuchandakar@yahoo.com 
Dr Srinivas Chakravarthy   Apollo Hospital  Jubilee Hills,-500033
Hyderabad
ANDHRA PRADESH 		 04023554720
04023543270
hydaherf@gmail.com 
Dr Sankar Srinivasan  Apollo Speciality Hospital  Padma Complex, Mount Road,,320, Anna Salai, Nandamnam, Teymapet-600035
Chennai
TAMIL NADU 		 04424331741
0442436242
ashaherf@gmail.com 
Dr.Chanchal Goswami  B. P. Poddar Cancer Institute  71/1, Humayun Kabir Sarani,,Block - G, New Alipore,-700053
Kolkata
WEST BENGAL 		 033 24458901
033 24577009
chanchalg@sify.com 
Dr.Jaydip Biswas  Chittaranjan National Cancer Institute  37, S.P. Mukherjee Road,-700026
Kolkata
WEST BENGAL 		 033 24759313
033 24757606
med_partha@yahoo.com 
Dr.Ravikumar Saxena  Global Hospitals  Lakadi-ka-pul,-500004
Hyderabad
ANDHRA PRADESH 		 040 23244444 Ext - 522
040 23233166
ravikumar1960@hotmail.com 
DR. Lokanatha Dasappa  Kidwai Memorial Institute of Oncology  Dr.M.H. Marigowda Road,-560029
Bangalore
KARNATAKA 		 080 26579503
080 26565671
drloku@hotmail.com 
Dr.Ganapathi Raman  Kumaran Hospital  214, P.H.Road,-600010
Chennai
TAMIL NADU 		 098404100194
044 26427701
sgrsowmya@yahoo.com 
Dr. Sachin Almel  P. D. Hinduja National Hospital and Research Centre  89F, Veer Savarkar Marg,,Mahim (West),-400016
Mumbai
MAHARASHTRA 		 022 24447006
022 24449151
svalmel@yahoo.com 
Dr Choondal Devan Sivanandan  Regional Cancer Centre  Medical College Campus,,P. O. No. 2417,-695011
Thiruvananthapuram
KERALA 		 04712522334
04712443498
webmaster@rcctvm.org 
Dr. Rajiv Ranjan Prasad  Regional Cancer Centre, Indira Gandhi Institute of Medical S  Medical Oncology,Sheikhpura-800014
Patna
BIHAR 		 0612 2295116
0612 2295119
rajiv_rprasad@yahoo.com 
Dr.Chetan Deshmukh  Ruby Hall Clinic  New Cancer Building, 3rd Floor,40 Sassoon Road-411001
Pune
MAHARASHTRA 		 020 66455605
020 66455605
inamdarshriram@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 11  
Name of Committee  Approval Status 
Clinical research Ethics Committee - PD Hinduja National Hospital and Medical Research Centre  Approved 
CRRT - Kumaran Hospital Ethics Committee  Approved 
Ethics Committee - Apollo Hospital, Hyderabad  Approved 
Ethics Committee - Poona Medical Research Foundation  Approved 
Institute Ethics Committee - Global Hospitals, Hyderabad  Approved 
Institute Ethics Committee - Indira Gandhi Institute of Medical Sciences  Approved 
Institutional Ethics Committee - Apollo Gleneagles Hospital, Kolkatta  Approved 
Institutional Ethics Committee - Apollo Hospitals, Chennai  Approved 
Institutional Ethics Committee - B.P. Poddar Hospital & Medical Research Ltd  Approved 
Institutional Ethics Committee - CNCI, Kolkata  Approved 
Medical Ethics Committee - KIDWAI MEMORIAL INSTITUTE OF ONCOLOGY  Approved 
 
Regulatory Clearance Status from DCGI
Modification(s)  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied
Modification(s)  
Health Type  Condition 
Patients  Metastatic gastric cancer,  
 
Intervention / Comparator Agent
Modification(s)  
Type  Name  Details 
Intervention  IMC-1121B of 5 mg/mL or 10 mg/mL  administered as an intravenous infusion at 8 mg/kg every 2 weeks in the absence of disease progression, toxicity requiring cessation, withdrawn consent, or other withdrawal criteria. 
Comparator Agent  Placebo: of 5 mg/mL or 10 mg/mL  administered as an intravenous infusion at 8 mg/kg every 2 weeks in the absence of disease progression, toxicity requiring cessation, withdrawn consent, or other withdrawal criteria. 
 
Inclusion Criteria
Modification(s)  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  Each patient must meet the following criteria to be enrolled in this study.

1. The patient has histologically- or cytologically-confirmed gastric carcinoma, including gastric adenocarcinoma or GEJ adenocarcinoma (patients with adenocarcinoma of the distal esophagus are eligible if the primary tumor involves the GEJ).

2. The patient has metastatic disease or locally recurrent, unresectable disease.

• Patients with nonregional lymph node metastases are eligible; lymph node metastases must be measurable as defined by the Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.0

• Patients with locally-recurrent, unresectable disease are eligible.

• For patients who have received prior radiation therapy, measurable or evaluable lesions must be outside the radiation field, or (for lesions within the radiation field) there must be documented progression following radiation therapy.

3. The patient has measurable disease and/or evaluable disease. Measurable disease is defined as at least one unidimensionally-measurable target lesion (≥ 20 mm with conventional techniques or ≥ 10 mm by spiral CT), as defined by RECIST Version 1.0. Examples of evaluable, nonmeasurable disease include gastric, peritoneal, or mesenteric thickening in areas of known disease, or peritoneal nodules that are too small to be considered measurable by RECIST.

4. The patient has experienced disease progression during or within 4 months after the last dose of first-line therapy for metastatic disease, or during or within 6 months after the last dose of adjuvant therapy.

• Acceptable first-line regimens for this study are combination chemotherapy regimens that include platinum or fluoropyrimidine components (acceptable prior platinum agents are cisplatin, carboplatin, or oxaliplatin; acceptable prior fluoropyrimidine agents are 5-FU, capecitabine, or S-1).

• Elevations in carcinoembryonic antigen or other tumor markers without radiographic evidence of progression do not constitute satisfactory evidence of progression on first-line therapy.

• Patients who are intolerant to first-line chemotherapy regimens are eligible provided there is disease progression within 4 months after the last dose of firstline therapy.

• Patients who have had one or more component(s) of first-line chemotherapy discontinued because of toxicity, but continued to receive the other component(s) of first-line therapy (eg, a FOLFOX regimen in which the oxaliplatin was stopped and the 5-FU/leucovorin was continued), are eligible following disease progression.

• Prior adjuvant therapy is permitted, and patients with disease progression during adjuvant chemotherapy are eligible, provided that disease progression occurs within 6 months after the completion of adjuvant therapy. Patients who experience disease progression more than 6 months after the last dose of adjuvant therapy should receive first-line therapy for metastatic disease, with subsequent progression on first-line therapy a requirement for eligibility.

5. The patient’s disease is not amenable to potentially curative resection.

6. The patient is ≥ 18 years of age.

7. The patient has a life expectancy of ≥ 12 weeks.

8. The patient has resolution to Grade ≤ 1 (or to Grade ≤ 2 in the case of neuropathy) by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.02, of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy (with the exception of alopecia).

9. The patient has an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0-1.

10. The patient has adequate hepatic function as defined by a total bilirubin ≤ 1.5 mg/dL (25.65 μmol/L), and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x the upper limit of normal (ULN) [or 5.0 x the ULN in the setting of liver metastases].

11. The patient has adequate renal function as defined by a serum creatinine ≤ 1.5 x the ULN, or creatinine clearance (measured via 24-hour urine collection) ≥ 40 mL/minute (ie, if serum creatinine is > 1.5 x the ULN, a 24-hour urine collection to calculate creatinine clearance must be performed).

12. The patient’s urinary protein is ≤ 1+ on dipstick or routine urinalysis ([UA]; if urine dipstick or routine analysis is ≥ 2+, a 24-hour urine collection for protein must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study).

13. The patient has adequate hematologic function, as evidenced by an absolute neutrophil count (ANC) ≥ 1000/μL, hemoglobin ≥ 9 g/dL (5.58 mmol/L), and platelets ≥ 100,000/μL.

14. The patient must have adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5 and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy). Patients on full-dose anticoagulation must be on a stable dose (minimum duration 14 days) of oral anticoagulant or low molecular weight heparin. If receiving warfarin, the patient must have an INR ≤ 3.0 and no active bleeding (ie, no bleeding within 14 days prior to first dose of study therapy) or pathological condition present that carries a high risk of bleeding (eg, tumor involving major vessels or known varices). Patients on anticoagulation therapy with unresected primary tumors or local tumor recurrence following resection are not eligible.

15. If the patient has received prior anthracycline therapy as part of his or her first-line regimen, the patient is able to engage in ordinary physical activity without significant fatigue or dyspnea (equivalent to New York Heart Association Class I function).[57]

16. Because the teratogenicity of IMC-1121B is not known, the patient, if sexually active, must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods).

17. Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization.

18. The patient is able to provide informed written consent and is amenable to compliance with protocol schedules and testing. 
 
ExclusionCriteria 
Details  Patients who meet any of the following criteria will be excluded from the study.

1. The patient has documented and/or symptomatic brain or leptomeningeal metastases.

2. The patient has experienced any Grade 3-4 gastrointestinal bleeding within 3 months prior to randomization.

3. The patient has experienced any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to randomization.

4. The patient has an ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, uncontrolled thrombotic or hemorrhagic disorder, or any other serious uncontrolled medical disorders in the opinion of the investigator.

5. The patient has ongoing or active psychiatric illness or social situation that would limit compliance with study requirements.

6. The patient has uncontrolled or poorly-controlled hypertension despite standard medical management.

7. The patient has a serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to randomization.

8. The patient has received chemotherapy, radiotherapy, immunotherapy, or targeted therapy for gastric cancer within 2 weeks prior to randomization.

9. The patient has received any investigational therapy within 30 days prior to randomization.

10. The patient has undergone major surgery within 28 days prior to randomization, or subcutaneous venous access device placement within 7 days prior to randomization.

11. The patient has received prior therapy with an agent that directly inhibits VEGF or VEGFR-2 activity (including bevacizumab), or any antiangiogenic agent.

12. The patient is receiving chronic antiplatelet therapy, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325 mg/day) is permitted.

13. The patient has elective or planned major surgery to be performed during the course of the clinical trial.

14. The patient has a known allergy to any of the treatment components.

15. The patient is pregnant or lactating.

16. The patient is known to be positive for infection with the human immunodeficiency virus.

17. The patient has known alcohol or drug dependency.

18. The patient has a concurrent active malignancy other than adequately-treated nonmelanomatous skin cancer, other noninvasive carcinoma, or in situ neoplasm. A patient with previous history of malignancy is eligible, provided that he/she has been free of disease for > 3 years. 
 
Method of Generating Random Sequence
Modification(s)  		 Computer generated randomization 
Method of Concealment
Modification(s)  		 Centralized 
Blinding/Masking
Modification(s)  		 Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded 
Primary Outcome
Modification(s)  
Outcome  TimePoints 
Evaluate the overall survival (OS) of patients with metastatic gastric cancer (including adenocarcinomas of the gastroesophageal junction [GEJ]) following disease progression on first-line platinum- or fluoropyrimidine-containing combination chemotherapy who undergo treatment with the MAb IMC-1121B plus BSC versus placebo plus BSC.  The time point of disease progression is evaluated at the point in time when clinically recorded and overall survival at the time of death. 
 
Secondary Outcome  
Outcome  TimePoints 
To evaluate the progression-free survival (PFS), including 12-week PFS rate, associated with IMC-1121B versus placebo ? To evaluate the objective response rate (ORR) ? To evaluate the duration of response ? To evaluate the quality of life (QoL) ? To evaluate the safety profile of IMC-1121B ? To examine the pharmacodynamic profile of IMC-1121B ? To assess the immunogenicity of IMC-1121B    
 
Target Sample Size
Modification(s)  		 Total Sample Size="348"
Sample Size from India="30" 
Final Enrollment numbers achieved (Total)= ""
Final Enrollment numbers achieved (India)="" 
Phase of Trial
Modification(s)  		 Phase 3 
Date of First Enrollment (India)
Modification(s)  		 20/12/2010 
Date of Study Completion (India) Date Missing 
Date of First Enrollment (Global)  06/10/2009 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial
Modification(s)  		 Years="4"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Completed 
Recruitment Status of Trial (India)  Completed 
Publication Details    
Individual Participant Data (IPD) Sharing Statement

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

Brief Summary
Modification(s)  		 Placebo-controlled, multicenter Phase 3 study of 615 patients with metastatic gastric cancer (including adenocarcinomas of the gastroesophageal junction) and disease progression on standard first-line chemotherapeutic regimens. Patients will be randomized on a 2:1 basis to receive BSC plus IMC-1121B administered every 2 weeks or BSC plus placebo administered every 2 weeks, respectively. Patients will undergo radiographic assessment of disease status every 6 weeks. Patients will be treated until there is evidence of progressive disease (PD), toxicity requiring cessation, withdrawal of consent, or until other withdrawal criteria are met. For India: 14 sites and estimated to randomize 30 pts. Tentative randomization start in India: 15 September 2010. 
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