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CTRI Number  CTRI/2008/091/000017 [Registered on: 22/10/2008]
Last Modified On: 03/04/2013
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study
Modification(s)  
Drug
Other (Specify) [Sorafenib 200mg/Matching placebo Tablets ]  
Study Design  Randomized, Parallel Group, Placebo Controlled Trial 
Public Title of Study   A study to determine the safety and activity of Sorafenib in patients with locally recurrent or metastatic breast cancer 
Scientific Title of Study   A Double-Blind, Randomized Phase 2b Study Evaluating the Efficacy and Safety of Sorafenib Compared to Placebo when Administered in Combination with Paclitaxel in Patients with Locally Recurrent or Metastatic Breast Cancer 
Secondary IDs if Any  
Secondary ID  Identifier 
NCT00499525  ClinicalTrials.gov 
NU07B1  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)  
Name  Ms Jamila Joseph 
Designation  Head Clinical Research Services 
Affiliation  Reliance Life Sciences Pvt. Ltd. 
Address  Thane-Belapur Road, Rabale,

Mumbai
MAHARASHTRA
400701
India 
Phone  919867610890  
Fax  912267678299  
Email  Jamila.Joseph@ril.com  
 
Details of Contact Person
Scientific Query

Modification(s)  
Name  Ms Jamila Joseph 
Designation  Head Clinical Research Services 
Affiliation  Reliance Life Sciences Pvt. Ltd. 
Address  Thane-Belapur Road, Rabale, Mumbai, Maharashtra - 400701, India

Mumbai
MAHARASHTRA
400701
India 
Phone  919867610890  
Fax  912267678299  
Email  JamilaJoseph@ril.com  
 
Details of Contact Person
Public Query

Modification(s)  
Name  Ms Jamila Joseph 
Designation  Head Clinical Research Services 
Affiliation  Reliance Life Sciences Pvt. Ltd. 
Address  Thane-Belapur Road, Rabale, Mumbai, Maharashtra - 400701, India

Mumbai
MAHARASHTRA
400701
India 
Phone  919867610890  
Fax  912267678299  
Email  Jamila.Joseph@ril.com  
 
Source of Monetary or Material Support  
Onyx Pharmaceuticals, Inc., (“Onyx”), USA 2100 Powell Street Emeryville, CA 94608  
 
Primary Sponsor
Modification(s)  
Name  William J Gradishar Feinberg School of MedicineChicago Illinois USA 
Address  Onyx Pharmaceuticals, 249, East Ground Avenue, South San Francisco CA 94608 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor
Modification(s)  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study
Modification(s)  
No of Sites = 20  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr K Pavitran  Amrita Institute of Medical Sciences, Kochi  Department of Medical Oncology, Amrita Institute of Medical Sciences, Elamakkara P.O., Kochi - 682026

 
44842853191
4842802177
pavitrank@aims.amrita.edu 
DrP K Das  Apollo Hospital Educational & Research Foundation, New Delhi   Apollo Hospital Educational & Research Foundation, Basement Hostel Complex, Indraprastha Apollo Hospitals, Sarita Vihar, NewDelhi- 110076
New Delhi
DELHI 
919810444600
911141677024
aherfdelhi@gmail.com 
DrRanjan Kumar Mohapatra  Apollo Specialty Hospital, Chennai  Apollo Specialty Hospital, #3, Globe Building( 3rd Floor), Rathna Nagar, Teynampet, Chennai- 600035
Chennai
TAMIL NADU 
914424354956
914424362424
realpv60@hotmail.com 
Dr Rathesan  Breast cancer clinic,Regional Cancer Centre, Trivandrum  Breast Cancer Clinic, Regional cancer Center, Trivandrum 695011.

 
919847203477
914712443498
ratheesan_k@yahoo.com 
Dr Smita Gupte  Cancer Clinic, Nagpur  Medical Oncologist & Hematologist, Cancer Clinic, 208 Shreewardhan Complex, Wardha Road, Nagpur - 440010
Nagpur
MAHARASHTRA 
919373107176
917122444729
smita_gupte@rediffmail.com 
Dr D Raghunadhrao  Department of Medical Oncology,Nizam’s Institute of Medical Sciences, Hyderabad   Head of Medical Oncology, Room 607, E block,6thFloor, Nizams Institute of Medical Sciences, Panjagutta, Hyderabad 500082.
Hyderabad
ANDHRA PRADESH 
919246571537
914023371747
telerama@rediffmail.com 
DrV Srinivasan  Dr.Kamakshi Memorial Hospital, Chennai  Dr. Kamakshi Memorial Hospital, No. 1, Radial Road, Pallikaranai, Chennai- 600091
Chennai
TAMIL NADU 
919841022366
914422463282
srinikmh@yahoo.co.in 
DrVinod Raina  Institute Rotary Cancer Hospital, AIIMS, New Delhi  Medical Oncology,Head Delhi Cancer Registry, Room no.- 401, Fourth Floor, Institute Rotary Cancer Hospital, AIIMS, NewDelhi- 110029
New Delhi
DELHI 
919811680638
911126588408
vinodraina@hotmail.com 
Dr S H Advani  Jaslok Hospita and Research Centre, Mumbai  Jaslok Hospital & Research Centre, 15 , Dr. G.Deshmukh Marg, Mumbai -400 026.
Mumbai
MAHARASHTRA 
9166573232
9123526833
shadvani2000@yahoo.com 
DrTarini Prasad Sahoo  Jawaharlal Nehru Cancer Hospital and Research Centre, Bhopal  Jawaharlal Nehru Cancer Hospital and Research Centre, Idgah hills, Bhopal-1, M.P, 462 001 India
Bhopal
MADHYA PRADESH 
919893686246
917552738325
tarini73@rediffmail.com 
DrKirshna Prasad  Kasturba Medical College Hospital, Mangalore   Department of Medical Oncology,Kasturba Medical College Hospital,Attavar,Mangalore - 575001
Bangalore
KARNATAKA 
919880345666
918242425092
drkrishnaprasad@hotmail.com 
DrLokanatha  Kidwai Memorial Institute of Oncology, Bangalore  Jindal Project Room. Kidwai Memorial Institute of Oncology,Dr.M.H.Merigowda Road, Bangalore - 560029.
Bangalore
KARNATAKA 
9845695589
918026565671
drloku@hotmail.com 
Dr Jitendra Kumar Singh  Mahaveer Cancer Sansthan, Patna  Mahaveer Cancer Sansthan, Phulwari Sharif, Patna - 801 505, India
Patna
BIHAR 
919431021001
9106122253957
drjksingh147@hotmail.com 
DrMinish Jain  Ruby Hall Clinic, Pune  Medical Oncologist, New Cancer Building, Ruby Hall Clinic, 40 Sassoon Road,Pune- 411001
Pune
MAHARASHTRA 
919823133390
912026124529
minishjain009@rubyhall.com 
Dr Shailesh Bondarde  Shatabdi Super Specialty Hospital, Nashik  Shatabadi Super Speciality,Opp Mahamarg Bus Stand, Mumbai naka, Nashik 422005

 
919822012427
912532501888
shaileshbondarde@yahoo.com 
DrShyam Aggarwal  Sir Ganga Ram Hospital, New Delhi  Room 212A, Department of Medical Oncology,Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi-110060.
New Delhi
DELHI 
919811075870
911125861002
drshyam_aggarwal@yahoo.com 
DrSomesh Chandra  Sterling Hospital, Ahmedabad  Surgical Oncologist, Sterling Hospital, Memnagar, Ahmedabad, Pin - 380052, India.
Ahmadabad
GUJARAT 
919426014627
917940011622
somesh@sterlinghospitals.com 
DrReena Nair  Tata Memorial Center, Parel  Dept. of Medical Oncology, OPD no. 14, Tata Memorial Center, Parel, Mumbai 400012
Mumbai
MAHARASHTRA 
912224177171
91222416549
reenanair@email.com 
Dr Kirti Patel  The Gujarat Cancer and Research Centre, Ahmedabad  Department of Medical Oncology, The Gujarat Cancer and Research Centre, Civil Hospital Campus, Asarwa, Ahmedabad-380016
Ahmadabad
GUJARAT 
919825386037
917922680662
drkirtimpatel@yahoo.co.in 
DrBhavin Shah  Vedanta Institute of Medical sciences, Ahmedabad  Hemato Oncology Clinic,Vedanta Institute of Medical sciences, Stadium to commerce College Road, Navrangpura. Ahmedabad, 380 009

 
919825327101
917940042225
dr_bhavin@hotmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 20  
Name of Committee  Approval Status 
Apollo Specialty Hospital, #3, Globe Building( 3rd Floor), Rathna Nagar, Teynampet, Chennai- 600035  Approved 
CREC, Madhav Niwas, Opposite Octroi Naka, Hingna Road, Nagpur - 440019  Approved 
Dr. Kamakshi Memorial Hospital, No. 1, Radial Road, Pallikaranai, Chennai- 600091  Approved 
Ethics Committee - Director, Mahaveer Cancer Sansthan, Phulwari Sharif, Patna - 801 505, India  Approved 
Ethics Committee Apollo Hospital Educational & Research Foundation, Basement Hostel Complex, Indraprastha Apollo Hospitals, Sarita Vihar, NewDelhi- 110076  Approved 
Ethics Committee, Jaslok Hospital & Research Centre, 15 , Dr. G.Deshmukh Marg, Mumbai -400 026.  Approved 
Ethics committee, Professor of Medical Oncology,Head Delhi Cancer Registry, Room no.- 401, Fourth Floor, Institute Rotary Cancer Hospital, AIIMS, NewDelhi- 110029  Approved 
Ethics Committee, Room 212A, Department of Medical Oncology,Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi-110060.  Approved 
Ethics Committee, The Gujarat Cancer and Research Centre, Civil Hospital Campus, Asarwa, Ahmedabad-380016  Approved 
EthicsCommittee, Additional Professor, Breast Cancer Clinic, Regional cancer Center, Trivandrum 695011  Approved 
Heart Care Clinic, Hemato Oncology Clinic,Vedanta Institute of Medical sciences, Stadium to commerce College Road, Navrangpura. Ahmedabad, 380 009  Approved 
Institute Ethics Committee,Department of Medical OncologyThe Gujarat Cancer and Research Centre, Civil Hospital Campus, Asarwa, Ahmedabad-380016  Approved 
Institutional Ethics Committee, Department of Medical Oncology,Kasturba Medical College Hospital,Attavar,Mangalore-575001  Approved 
Institutional Ethics Committee, Jawaharlal Nehru Cancer Hospital and Research Centre, Idgah hills, Bhopal-1, M.P, 462 001 India  Approved 
Institutional Ethics Committee, Nizams Institute of Medical Sciences, Panjagutta, Hyderabad 500082.   Approved 
Kidwai Memorial Institute of Oncology,Dr.M.H.Merigowda Road, Bangalore 560029.  Approved 
Poona Medical Research Foundation, Medical Oncologist, New Cancer Building, Ruby Hall Clinic, 40 Sassoon Road,Pune- 411001  Approved 
Shatabadi Super Speciality,Opp Mahamarg Bus Stand, Mumbai naka, Nashik 422005  Approved 
Sterling Hospital Ethics Committee, Memnagar, Ahmedabad, PIN- 380052, India  Approved 
The Institutional Ethics Committee, Department of Medical Oncology, Amrita Institute of Medical Sciences, Elamakkara P.O., Kochi - 682026  Approved 
 
Regulatory Clearance Status from DCGI
Modification(s)  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied
Modification(s)  
Health Type  Condition 
Patients  Patients with locally recurrent or metastatic breast cancer,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Placebo  Matching placebo tablets 
Intervention  Sorafenib  200 mg tablets 
 
Inclusion Criteria
Modification(s)  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Female 
Details 
Note: No upper age limit for this clinical trial, (indicated as 18 years and above)

1. Histologically or cytologically confirmed adenocarcinoma of the breast.
2. Measurable or evaluable locally recurrent or metastatic disease. (Locally recurrent disease must not be amenable to resection with curative intent.) All scans used to document measurable or evaluable disease must be done within 4 weeks prior to randomization.
3. Age greater than or equal to 18 years
4. Patients must not have had adjuvant or neoadjuvant taxane therapy within 12 months of randomization.
5. Patients must have discontinued other adjuvant chemotherapy at least 3 weeks prior to randomization.
6. Prior hormonal therapy for locally recurrent or metastatic disease is allowed.
7. Prior radiation therapy is allowed but must be completed at least 3 weeks prior to randomization. Previously radiated area(s) must not be the only site of disease.
8. ECOG Performance Status of 0 or 1
9. Adequate bone marrow, liver, and renal function as assessed by the following:
- Hemoglobin greater than or equal to 9.0 g/dl
- Absolute neutrophil count (ANC) greater than or equal to 1,500/mm3
- Platelet count greater than or equal to100,000/mm3
- Total bilirubin less than or equal to 2.0 times the upper limit of normal
- ALT and AST less than or equal to 2.5 x upper limit of normal (less than or equal to 5 x upper limit of normal for patients with liver involvement)
- International Normalized Ratio for Prothrombin Time (PT-INR) and activated partial prothrombin time (aPTT) less than or equal to 1.5 times the upper limit of normal for patients NOT on blood thinners. NOTE: Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin will have a higher value but may be allowed to participate as long as the INR is measured prior to initiation of sorafenib/placebo and is monitored at least weekly, or as defined by the local standard of care, until INR is stable.
- Creatinine less than or equal to 2.0 times the upper limit of normal
10. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to randomization and must agree to use adequate contraception prior to randomization and for the duration of study participation.
11. Patients must be able and willing to sign a written informed consent. A signed informed consent must be appropriately obtained prior to any study specific procedures.
12. Patients must be able to swallow and retain oral medication.
 
 
ExclusionCriteria 
Details  1. Patients with breast cancer over-expressing HER-2 (gene amplification by FISH or 3+ over-expression by immunohistochemistry). Patients with unknown HER-2 status are not eligible. 2. Patients with active brain metastases. Patients with neurological symptoms must undergo a contrast computed tomography (CT) scan or magnetic resonance imaging (MRI) of the brain to exclude active brain metastasis. Patients with treated brain metastases are eligible provided they have no evidence of brain disease and are off definitive therapy (including steroids) within 3 months prior to randomization. 3. Prior chemotherapy for locally recurrent or metastatic breast cancer 4. Major surgery, open biopsy, or significant traumatic injury within 4 weeks of randomization 5. Evidence or history of bleeding diathesis or coagulopathy 6. Serious, non-healing wound, ulcer, or bone fracture 7. Substance abuse, or medical, psychological, or social condition that may interfere with the patient?s participation in the study or evaluation of the study results 8. Pre-existing peripheral neuropathy ≥Grade 2 9. Use of cytochrome P450 enzyme-inducing anti-epileptic drugs (such as phenytoin, carbamazepine, or phenobarbital) 10. Clinically significant cardiac disease including congestive heart failure > class II NYHA (see Appendix IV), unstable angina (angina symptoms at rest) or new-onset angina (begun within the last 3 months), myocardial infarction within the past 6 months prior to randomization 11. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy and or uncontrolled hypertension (systolic blood pressure >150 mmHg or diastolic pressure >90 mmHg) despite optimal medical management 12. Thrombolic, embolic, venous, or arterial events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months. No pulmonary hemorrhage/bleeding event > NCI-CTCAE Grade 2 within 4 weeks of randomization. No other hemorrhage/bleeding event greater than or equal to CTCAE Grade 3 within 4 weeks of randomization 13. Active clinically serious infection > NCI-CTCAE Grade 2 14. Known human immunodeficiency virus infection or chronic hepatitis B or C 15. Previous or concurrent cancer that is distinct in primary site or histology from breast cancer within 5 years prior to randomization EXCEPT cervical cancer in situ, treated basal cell carcinoma, superficial bladder tumors [Ta and Tis]. 16. Known or suspected allergy to sorafenib or hypersensitivity to paclitaxel or drugs using the vehicle Cremophor 17. Use of St. John?s Wort or rifampin (rifampicin) within 1 week of randomization 18. Prior treatment with bevacizumab or any other drugs (licensed or investigational) that target VEGF or VEGF-R 19. Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy or tumor embolization) other than paclitaxel and sorafenib/placebo 20. Women that are pregnant or breast feeding 21. Use of any investigational drug within 30 days or 5 half-lives, whichever is longer, preceding randomization  
 
Method of Generating Random Sequence   Stratified randomization 
Method of Concealment   Centralized 
Blinding/Masking   Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded 
Primary Outcome  
Outcome  TimePoints 
To compare progression free survival (PFS) in patients with sorafenib and paclitaxel versus patients treated with placebo and paclitaxel as a first-line therapy for locally recurrent or metastatic breast cancer  Events projected to occur November 2008 
 
Secondary Outcome  
Outcome  TimePoints 
1. To compare the objective response rate, duration of response, time to progression, and survival of patients treated with sorafenib and paclitaxel versus placebo and paclitaxel. 2. To compare the safety of patients treated with sorafenib and paclitaxel versus placebo and paclitaxel   Overall survival events projected to occur August 2010 
 
Target Sample Size
Modification(s)  
Total Sample Size="220"
Sample Size from India="170" 
Final Enrollment numbers achieved (Total)= ""
Final Enrollment numbers achieved (India)="" 
Phase of Trial   Phase 2 
Date of First Enrollment (India)
Modification(s)  
05/05/2008 
Date of Study Completion (India) Date Missing 
Date of First Enrollment (Global)  10/03/2008 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="4"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Completed 
Recruitment Status of Trial (India)  Completed 
Publication Details    
Brief Summary   It is a global multicenter trial. USA is the only other participating country other than India. Approvals are already in place from the concerned regulatory authorities including India. The study was filed under US IND. The US FDA after reviewing the IND submitted for this study concluded that the trial meets all the requirements for the exemptions from the IND regulations. Approval from US FDA with respect to exemption from the IND regulation (21 CFR § 312.2) for the referenced study is provided. A total of 220 patients will be randomly assigned (1:1 ratio) to receive either sorafenib and paclitaxel or placebo and paclitaxel. The trial is currently recruiting patients across 33 sites participating in the study from USA. Sponsor proposes to enroll 170 patients from India from up to 20 participating sites. A double-blind, randomized, Phase 2b trial in approximately 220 patients (greater than or equal to 18 years of age) with locally recurrent or metastatic breast cancer. The study will consist of a screening period, a treatment period, and a follow-up period. Screening Period Treatment Period Patients will be randomly assigned in a 1:1 ratio to sorafenib and paclitaxel or placebo and paclitaxel. During the randomization process, patients will be stratified by site of metastatic disease: visceral disease versus nonvisceral (osseous or soft tissue) disease. Randomization will be performed using a web-based randomization and product inventory control system (RPIC) provided by a third-party vendor. Follow-up Period Patients will enter the follow-up period upon documentation of disease progression, extraordinary medical circumstances, intolerable toxicities, or withdrawal of consent. Every reasonable effort should be taken to encourage patients to continue to be followed for evidence of disease progression even after study treatment discontinuation for reasons other than progressive disease. All patients will be followed for survival until the planned number of events for survival (120 deaths) has been reached. Assessment of survival will be performed approximately every 4 months. Duration of Treatment: Patients will receive study treatment until disease progression is documented, extraordinary medical circumstances occur, intolerable toxicities occur, or the patient withdraws consent. The primary objective is to compare progression free survival (PFS) in patients with sorafenib and paclitaxel versus patients treated with placebo and paclitaxel as a first-line therapy for locally recurrent or metastatic breast cancer The secondary objectives are: 1. To compare the objective response rate, duration of response, time to progression, and survival of patients treated with sorafenib and paclitaxel versus placebo and paclitaxel. 2. To compare the safety of patients treated with sorafenib and paclitaxel versus placebo and paclitaxel  
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