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CTRI Number  CTRI/2015/03/005653 [Registered on: 25/03/2015] Trial Registered Retrospectively
Last Modified On: 19/05/2015
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Crossover Trial 
Public Title of Study   A randomized, open label, multi centric, 2 treatment, 2 period, 2 sequence, single dose, crossover, BE study of Paclitaxel protein-bound particles for injectable suspension 100mg/vial and Abraxane 100mg/vial (Albumin bound Paclitaxel 260mg/m2) IV infusion in patients with metastatic breast cancer  
Scientific Title of Study   A randomized, open label, multi centric, two treatment, two period, two sequence, single dose, crossover, bioequivalence study of Paclitaxel protein-bound particles for injectable suspension (albumin-bound) 100 mg/vial manufactured by Sindan Pharma for Actavis LLC, USA and Abraxane 100 mg/vial (Albumin bound Paclitaxel 260 mg/m2) intravenous infusion Abraxis BioScience LLC, New Jersey in patients with metastatic breast cancer 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
ACTA/PAC/2013 Version 4 February 10, 2015  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Mr Bhupesh SPednekar 
Designation  Project Manager 
Affiliation  Lotus Labs Pvt. Ltd 
Address  Lotus House # 07, Jasma Bhavan Road Millers Tank Bed Area Opp. Guru Nanak Bhavan Vasanth Nagar Bangalore

Bangalore
KARNATAKA
560 052
India 
Phone  42708400  
Fax    
Email  saravanan_g@lotuslabs.com  
 
Details of Contact Person
Scientific Query
 
Name  DrSharath Sekar Shivamogga 
Designation  Medical advisor 
Affiliation  Lotus Labs Pvt. Ltd 
Address  Lotus House # 07, Jasma Bhavan Road Millers Tank Bed Area Opp. Guru Nanak Bhavan Vasanth Nagar Bangalore

Bangalore
KARNATAKA
560 052
India 
Phone  08042708400  
Fax    
Email  sharath_ss@lotuslabs.com  
 
Details of Contact Person
Public Query
 
Name  DrSharath Sekar Shivamogga 
Designation  Medical advisor 
Affiliation  Lotus Labs Pvt. Ltd 
Address  Lotus House # 07, Jasma Bhavan Road Millers Tank Bed Area Opp. Guru Nanak Bhavan Vasanth Nagar Bangalore


KARNATAKA
560 052
India 
Phone  08042708400  
Fax    
Email  sharath_ss@lotuslabs.com  
 
Source of Monetary or Material Support  
Actavis LLC Morris Corporate Center III 400 Interpace Parkway Parsippany, NJ 07054 USA 
 
Primary Sponsor  
Name  Actavis LLC 
Address  Morris Corporate Center III 400 Interpace Parkway, Parsippany, NJ 07054 USA 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 9  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Singaraju Mallik  BIBI General Hospital and Cancer Centre  Room no. 308, Department of Radiation Oncology, 3rd floor, BIBI General Hospital and Cancer Centre, 16-3-991/1/C, Government Printing Press Road, Malakpet, Hyderabad-500024, Telangana, India.
Hyderabad
ANDHRA PRADESH 
04024528144

drmallik.onco@gmail.com 
Dr Gururaj Deshpande  City Cancer Centre  Department of Surgical Oncology, 1st floor, City Cancer Centre, 33-25-33, Suryarao Pet, Vijaywada-520002, Andhra Pradesh, India
Krishna
ANDHRA PRADESH 
08662436661

drgururajdeshpande@gmail.com 
Dr Krishnan  Dr. Rai Memorial Medical Centre  Department of Oncology, Basement floor, Dr. Rai Memorial Medical Centre, No: 562, Century Plaza, Anna Salai, Teynampet, Chennai-600061, Tamilnadu, India
Chennai
TAMIL NADU 
044-24349860

krishnan_dr@yahoo.com 
Dr Arun Seshachalam  GVN Cancer Institute (a Unit of GVN Hospital)  Department of Medical Oncology, ground floor, GVN Cancer Institute (a Unit of GVN Hospital), No. 46, Singarathope, Trichy - 620 008. Tamil Nadu, India
Tiruchirappalli
TAMIL NADU 
09626010005

drarunonco@gmail.com 
Dr Vijay Bhaskar  Meenakshi Mission Hospital and Research Centre  Department of Oncology, Meenakshi Mission Hospital and Research Centre, Lake Area, Melur Road, Madurai-625107, Tamilnadu, India.
Madurai
TAMIL NADU 
91-452-4263000

drvijaybhaskar@gmail.com 
Dr Minish Jain  Noble Hospital  Consultation OP room, 6th Floor, Department of Oncology, Noble Hospital 153, Magarpatta City Road Hadapsar Pune 411013, Maharashtra, India
Pune
MAHARASHTRA 
9823133390

minishjain009@gmail.com 
Dr Ghanshyam Biswas  Sparsh Hospital and Critical Care  Consultation Room No. 1, Department of Surgical Oncology, Ground Floor, Sparsh Hospital and Critical Care A/407, Sahid Nagar, Bhubaneshwar 751007, Orissa, India.
Khordha
ORISSA 
9937500878

drgbiswas@yahoo.com 
Dr CT Sateesh  Sri Venkateshwara Hospital  Consultation Room, 3rd Floor, Department of Medical Oncology, Sri Venkateshwara Hospital # 86, Hosur main road, Madiwala Bangalore 560068, Karnataka, India
Bangalore
KARNATAKA 
9686679406

smohyderabad@gmail.com 
Dr Lokanatha  Srinivasan Cancer Care Hospital  Consultation Room No. 1, Second Floor, Srinivasan Cancer Care Hospital, 236/1, 2nd floor, Vijayshree Layout, Arekere, Bannerghatta Road, Bangalore 560076, Karnataka, India.
Bangalore
KARNATAKA 
8026578557

drloku@hotmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 9  
Name of Committee  Approval Status 
BIBI Institutional Ethics Committee,   Approved 
City Cancer Centre  Approved 
Dr. GVN Cancer Institute Institutional Ethics Committee  Approved 
Dr. Rai Memorial Medical Centre Institutional Ethics Committee  Approved 
Meenakshi Mission Hospital and Research Centre  Approved 
Noble Hospital   Submittted/Under Review 
Sparsh Hospital and Critical Care  Approved 
Sri Venkateshwara Hospital Ethics Committee  Approved 
Srinivasan Cancer Care Hospital  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  Breast Cancer,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Abraxane 100 mg/vial (Albumin bound Paclitaxel) intravenous infusion  Abraxane 100 mg/vial (Albumin bound Paclitaxel) intravenous infusion Abraxis BioScience LLC, New Jersey Dose- 260 mg/m2, Frequency- In every 21 days (1 cycle), Mode of Administration-IV Duration of the trial- 8 months 
Intervention  Paclitaxel protein-bound particles for injectable suspension (albumin-bound) 100 mg/vial   Paclitaxel protein-bound particles for injectable suspension (albumin-bound) 100 mg/vial manufactured by Sindan Pharma for Actavis LLC, USA Dose- 260 mg/m2, Frequency- In every 21 days (1 cycle), Mode of Administration-IV Duration of the trial- 8 months 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  60.00 Year(s)
Gender  Female 
Details  i. Female patients aged between 18 - 60 years of age (inclusive) with histological or cytological confirmation of diagnosis of breast cancer.
ii.Female patients with metastatic breast cancer (No known CNS metastasis) after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated. If the patient is already receiving Paclitaxel, at least two more cycles of Paclitaxel should be required for completing the course of chemotherapy, for inclusion in the study.
iii. Life expectancy of more than 6 months as judged by the Investigator.
iv. ECOG (Eastern Cooperative Oncology Group) performance status of 2 or less.
v. Adequate renal function defined as Serum Creatinine ≤1.5 times ULN
vi. Previous chemotherapy and or radiotherapy should be completed 4 weeks prior to start of first IMP administration for the current study
vii. Previous hormonal treatment should be completely washed out prior to start of IMP administration
viii. Satisfactory medical assessment done by investigator to ensure that there are no clinically significant and relevant abnormalities (of medical history, physical examination and ECG, clinical or laboratory evaluation (haematology, biochemistry, serology and urinalysis). Patients must have Hemoglobin ≥ 9 gm/dl for inclusion in the study
ix. Postmenopausal women with amenorrhea for at least 12 consecutive months
x. Female patients of child bearing potential must agree to use one of the following contraceptive measures during and for at least three months after cessation of therapy:
a. Surgically sterile (bilateral tubal ligation, hysterectomy, bilateral oophorectomy).
b. IUD in place for at least 3 months.
c. Barrier methods (condom, diaphragm) with spermicide for at least 14 days prior to the first dose, throughout the study and for 4 days following the last dose.
d. Abstinence
e. Other birth control methods deemed acceptable by the investigator
xi. The patient must understand and be able, willing and likely to fully comply with study procedures and restrictions
xii. Patient must have provided signed and dated Informed consent given in written form in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6 and applicable regulations, before initiating any study-related procedures 
 
ExclusionCriteria 
Details  i. History or presence of significant current or recurrent disease (other than breast cancer) that could affect the action or disposition of the investigational product, or clinical or laboratory assessments.
ii. History or presence of significant current or relevant previous history of serious, severe or unstable (acute or progressive) physical or psychiatric illness, any medical disorder that may require treatment (other than breast cancer) or make the patient unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures.
iii. Patients requiring any concurrent chemotherapy, hormonal therapy, immunotherapy, therapy with biologicals or radiotherapy for the disease.
iv. Patients with medical conditions that preclude administration of chemotherapy [uncontrolled intercurrent illness like unstable angina, myocardial infarction (within 6 months prior to study entry), congestive heart failure, serious cardiac arrhythmias, uncontrolled diabetes, autoimmune disease, or any uncontrolled systemic disease (e.g. recurrent pleural effusion / ascites, active infections, patients with immune deficiency disorders) or patients already on immunosuppressive drugs] or any other significant co-morbid conditions as determined by the investigator (s).
v. Patients with liver impairment - serum transaminase levels (alanine transaminase [ALT] and/or aspartate transaminase [AST]) greater than 2.5 times the upper limit of normal (ULN) concurrent with serum alkaline phosphatase levels greater than 2.5 times the ULN
vi. Patients with absolute neutrophil count of < 1,500 cells/mm3 & platelet < 1,00,000 /mm3 during screening
vii. Serum albumin < 3 gm/dl
viii. Presence of Left ventricular ejection fraction (LVEF) of <50% as determined by Echocardiography (ECHO)/ Multiple Gated Acquisition scan (MUGA).
ix. Previous documented history of QTc prolongation with other medication or patient with congenital QT prolongation or patient with Patients with QTc ≥ 470 ms (where QTc based on Bazett’s correction method) or patient with any other significant cardiac disease.
x. Presence of left bundle branch block (LBBB) and with significant atrioventricular block (AV block).
xi. Current (within 2 weeks of the start of the study) or regular use of any medication (including over the counter [OTC], herbal or homeopathic preparations) that could affect (improve or worsen) the condition being studied, or could affect the action, absorption or disposition of the investigational product, or clinical or laboratory assessment.
xii. Clinical illness other than breast cancer, radiotherapy or any major surgery within 4 weeks before the start of the study.
xiii. Patients with known CNS metastasis.
xiv. Positive urine drug screening, HIV, VDRL/RPR, Hepatitis B & C tests.
xv. Patients with severe fluid retention e.g. pleural effusion, pericardial effusion or ascites.
xvi. Patients previously been randomized into this study and subsequently withdrawn
xvii. Known or suspected intolerance or Hypersensitivity to Paclitaxel or any of the excipients or any other taxane
xviii. Patients who have participated in any other clinical study in the preceding 30 days prior to the start of the study.
xix. Patients who are pregnant or demonstrating a positive pregnancy screen or are currently breast-feeding or planning to become pregnant during study period.
xx. Patient unable to be closely followed for social, Geographic or psychological reasons.
xxi. Patients who have taken medication that are either substrates or inhibitor/inducer of CYP3A4/CYP2C8 enzyme < 3 weeks prior to start of IP or require as concomitant medication
xxii. Patients with pre-existing sensory neuropathy of a severity > grade 3 as defined in National Cancer Institute Common Toxicity Criteria (CTC) 
 
Method of Generating Random Sequence   Other 
Method of Concealment   Other 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
Cmax, AUC0-t and AUC0-∞
• The study duration for each patient will be of approximately 50 days (14 days of screening+21 days of washout including P-I dosing +15 days of follow up period) 
0.250, 0.500, 0.750, 1.000, 1.500, 2.000, 3.000, 4.000, 6.000, 8.000, 12.000, 24.000, 48.000 72.00 and 96.000 
 
Secondary Outcome  
Outcome  TimePoints 
To summarize the treatment emergent adverse events in patients  Throughout the study 
 
Target Sample Size   Total Sample Size="60"
Sample Size from India="60" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   N/A 
Date of First Enrollment (India)   01/03/2015 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="0"
Months="8"
Days="0" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details    
Individual Participant Data (IPD) Sharing Statement

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

Brief Summary  

This study is a randomized, open label, two way cross over, bioequivalence study comparing Paclitaxel protein-bound particles for injectable suspension (albumin-bound) 100 mg/vial manufactured by Sindan Pharma for Actavis LLC, USA and Abraxane  100 mg/vial (Albumin bound Paclitaxel) intravenous infusion Abraxis BioScience LLC, New Jersey in Patients with metastatic breast cancer. This study will be conducted in multi centre sites in India. The primary objective of this study is to show bioequivalence of Paclitaxel protein-bound particles for injectable suspension (albumin-bound) 100 mg/vial manufactured by Sindan Pharma for Actavis LLC and Abraxane  100 mg/vial (Albumin bound Paclitaxel) intravenous infusion Abraxis BioScience LLC in patients with metastatic breast cancer.

Secondary objective is to summarize the treatment emergent adverse events in patients with metastatic breast cancer.
 
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