CTRI/2015/09/006156 [Registered on: 03/09/2015] Trial Registered Prospectively
Last Modified On:
26/11/2016
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
Bioequivalence study of Paclitaxel protein-bound particles for injectable 100 mg/vial of Cipla Ltd.,India with ABRAXANE® for Injectable Manufactured
for: Celgene Corporation Summit, USA in Metastatic Breast cancer patients after failure of Chemotherapy /relapse after prior Chemotherapy.
Scientific Title of Study
A multicenter, open label, randomized, balanced, two treatment,two period, two sequence, two way crossover, single dose,bioequivalence study of Paclitaxel protein-bound particles for
injectable suspension (albumin-bound) 100 mg/vial of Cipla Ltd.,India with ABRAXANE® for Injectable Suspension (paclitaxel
protein-bound particles for injectable suspension) Manufactured for: Celgene Corporation Summit, USA in Breast cancer patients
after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy.
Acharya Tulsi Regional Cancer Treatment & Research Institute
Department of Oncology, Acharya Tulsi Regional Cancer Treatment & Research Institute, S.P. Medical College, Bikaner- 334001, Rajasthan Bikaner RAJASTHAN
9782300231
shekhar@siaramresearch.com
Dr Basavraj Kadalge
Aster Aadhar Hospital
Department of Oncology, Aster Aadhar Hospital (Prerana Hospital Ltd.), R.S.No.628, B, Ward, Near Shastri Nagar, KMT workshop, Kolhapur- 416012, Maharashtra Kolhapur MAHARASHTRA
Department of Oncology, Dr. GVN Cancer Institute, No.46, Singarathope, Trichy-620008, Tamilnadu Tiruchirappalli TAMIL NADU
9345116080
xavier_onco@yahoo.com
Dr K Velavan
Erode Cancer Centre
Department of Oncology, Erode Cancer Centre, SH 96, Thindal, Erode-638012, Tamil Nadu Erode TAMIL NADU
9842822443
kvels@rediffmail.com
Dr Krishna Kamble
Government Medical College
Department of Radiation Threrapy and Oncology, Government Medical College Nagpur, Nagpur-440003, Maharashtra Nagpur MAHARASHTRA
9850246275
drkamble.onco@gmail.com
Dr Sandeep Tiwari
King George Medical College
Department of General Surgery and oncology, King George Medical College, , Lucknow - 226007,UP,India. Lucknow UTTAR PRADESH
941550733
sandeep-neelu@yahoo.co.in
Dr Rohan Bhise
KLES Dr. Prabhakar Kore Hospital & MRC
Department of Oncology, KLES Dr. Prabhakar Kore Hospital & MRC, Nehru nagar, Belagavi-59010, Karnataka Belgaum KARNATAKA
9448866712
rohanbhise30@gmail.com
Dr Yogesh Anap
Kolhapur Cancer Centre
Department of Oncology, Kolhapur Cancer Centre, R-S 238, Opposite Mayur Petrol Pump,Gokul Shirgao, Kolhapur-416234, Maharashtra Kolhapur MAHARASHTRA
9420635556
yogesh.anap1@gmail.com
Dr Sangeeta Jiwatani
Mangal Anand Hospital
Department of Oncology, Mangal Anand Hospital, 48, Swastik Park, Sion-Trombay Road, Chembur, Mumbai-400071, Maharashtra Mumbai MAHARASHTRA
8097681981
sangeetajiwatani@hotmail.com
Dr Kirushna Kumar
Meenakshi Mission Hospital
Department of Oncology,Meenakshi Mission Hospital, Lake Area, melur Road,, Madurai Nadu-625 107, Tamilnadu Madurai TAMIL NADU
09787713004
drkskk@yahoo.com
Dr Kaushal Patel
Nirmal Hospital
Department of Oncology, Nirmal Hospital, Ring road, Surat-395002, Gujarat Surat GUJARAT
99795300073
drkaushalbpatel@gmail.com
Dr Jitendra Kumar Singh
S S Hospital and Research Centre
Department of oncology,
S S Hospital and Research Centre, Doctor’s Colony,Malahi Pakri Chowk, Kankarbagh, Patna-800020 Patna BIHAR
9431021001
drjksingh147@hotmail.com
Dr Vinayak Shenage
Shatabdi Hospital
Department of Oncology, Shatabdi Hospital, Opp Mahamarg Bus Stand, Mumbai Naka, Nashik- 422005, Maharashtra Mumbai MAHARASHTRA
8087829000
drvinayakshenage@yahoo.com
Dr Jignesh Meva
Shree Giriraj Multispeciality Hospital
Department of Oncology, Shree Giriraj Multispeciality Hospital, 27, Navjyot Park corner, 150 ft Ring Road. Rajkot-360004, Gujarat Rajkot GUJARAT
9909007541
drjigneshmeva@gmail.com
Dr Lokesh K N
Sri Venkateshwara Hospital
Department of Oncology, Sri Venkateshwara Hospital , No. 86, madiwala, hosur Main Road, Bangalore – 560068, Karnataka Bangalore KARNATAKA
8971609070
svhospital1997@gmail.com
Dr Sudha Somappa
Srinivasam Cancer Care Hospital Pvt. Ltd
Department of Oncology, Srinivasam Cancer Care Hospital Pvt. Ltd, #236/vijayshree Layout Arelare, Bannergatta Main Road, Bangalore-566076, Karnataka Bangalore KARNATAKA
9972921196
sudhasomappa@gmail.com
Dr Rakesh Neve
Sterling Multispeciality Hospital
Department of Oncology, Sterling Multispeciality Hospital, Sector 27, Near Bhel Chowk, Pradhikaran, Nigdi, Pimpri-Chinchwad, Pune- 411044, Maharashtra Pune MAHARASHTRA
9225510913
drrneve@gmail.com
Dr Hitendra Ayre
Unique Hospital Multispecialty & Research Institute
Department of oncology, Unique Hospital Multispecialty & Research Institute, Opp. Kiran Motor, Nr. Canal, Civil Hospital Char Rasta - Sosyo Circle Lane, Off. Ring Road, Surat-395002, Gujarat Surat GUJARAT
9227230347
Hitendra_ayre@yahoo.com
Dr Shravan Tungenwar
United CIIGMA Institute of Medical Sciences Pvt Ltd
Department of Oncology, United CIIGMA Institute of Medical Sciences Pvt Ltd, Plot No. 6 & 7, Plot no. 10, Shahnoorwadi dargah road, Aurangabad- 431005, Maharashtra Aurangabad MAHARASHTRA
9763708445
drshravan.uch@gmail.com
Dr Mahesh Naik
Vintage Hospital & Medical Research Centre Pvt. Ltd
Department of Oncology, Vintage Hospital & Medical Research Centre Pvt. Ltd, Caculo Enclave, St. Inez, Panaji-403001, Goa North Goa GOA
Breast cancer patients after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy.,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Abraxane® for injectable suspension (Paclitaxel protein-bound particles
for injectable suspension) (albumin-bound) 100 mg/vial
Manufactured for: Celgene Corporation Summit, USA
Patients will receive 260mg/m2 dose of the study drug on the first day of the chemotherapy cycle [as per the randomisation sequence] for study duration 2 cycles
Dose- 260 mg/m2, Frequency- In every 21 days (1 cycle), Mode of Administration-IV
Intervention
Paclitaxel protein-bound particles for injectable suspension (albuminbound)
100 mg/vial
Manufactured by Cipla Ltd., India
Patients will receive 260mg/m2 dose of the study drug on the first day of the chemotherapy cycle [as per the randomisation sequence] for study duration 2 cycles
Dose- 260 mg/m2, Frequency- In every 21 days (1 cycle), Mode of Administration-IV
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Female
Details
1. Female patients, 18 to 65 years of age (both inclusive).
2. Has histological or cytological confirmed metastatic breast cancer after failure of combination chemotherapy for metastatic diseasem or has had a relapse within 6 months of adjuvant chemotherapy (Prior therapy should have included an anthracycline unless clinically contraindicated.).
3. Patients with life expectancy of at least 3 months as per the investigator opinion.
4. ECOG performance status of less and equal to 2.
5. Adequate hemopoeitic, renal and liver function.
Bone marrow function:
ANC more than and equal to 1500/mm3,
Platelet count more than and equal to 100,000/mm3
Hemoglobin more than and equal to 9.0 g/dl
Renal function Serum Creatinine more than 1.5 times ULN
Hepatic function:
AST and ALT less than and equal to 2.5 times ULN
Alkaline phosphatase less than 2 times ULN
Bilirubin less than and equal to 1.5 times ULN
6. All other clinical laboratory values deemed as not clinically significant by the Principal Investigator/Sub-Investigator.
7. Availability for the entire study duration and willingness to adhere to the
protocol requirements.
8. Capable of giving written informed consent prior to receiving any study
medication.
9. Women of childbearing potential must have a negative serum pregnancy test, must be using an adequate method of contraception and must be willing to avoid becoming pregnant during the study period. Female patients must fulfill at least one of the following:
• Be surgically sterile for a minimum of 6 months;
• Post-menopausal for a minimum of 1 year;
• Agree to avoid pregnancy and use medically acceptable method of contraception from at least 30 days prior to the study until 30 days after the study has ended (last study procedure).
• Medically acceptable methods of contraception include non-hormonal intrauterine device or double barrier method (condom with foam or vaginal
spermicidal suppository, diaphragm with spermicide).Complete abstinence
alone can be used as a method of contraception.
ExclusionCriteria
Details
1. History of allergy or hypersensitivity reactions to a Paclitaxel or the components of Paclitaxel protein-bound particles for injectable suspension(albumin-bound) or any related compound at any dose.
2. Known history or presence of any clinically significant hepatic, renal/genitourinary, gastrointestinal (e.g., intra-abdominal inflammation), cardiovascular (e.g., congestive heart failure, ventricular arrhythmia, myocardial infarction, unstable angina pectoris), cerebrovascular, pulmonary (e.g., interstitial lung disease), endocrine, immunological, musculoskeletal, neurological, psychiatric, dermatological or hematological (e.g., bleeding diathesis or coagulopathy) disease or condition other than cancer unless determined as not clinically significant by the Investigator.
3. History of any other malignancy within the last 5 years which could affect the diagnosis or assessment of breast cancer.
4. Sensory / Peripheral neuropathy of more than Grade 2 at baseline.
5. Presence of any significant physical or organ abnormality or active opportunistic infection (i.e. mycobacteria, cytomegalovirus, toxoplasma,
Pneumocystis carinii) as determined by the Investigator.
6. Patients not completely recovered from any toxicities from previous chemotherapy, hormonetherapy, immunotherapy, or radiotherapies less than or equal to Grade 1.
7. A positive test result for any of the following: HIV, Hepatitis B surface antigen, Hepatitis C, drugs of abuse and breath alcohol test.
8. Difficulty fasting or consuming standard meals.
9. Patients who are:
• Pregnant
• Breast feeding
• Of childbearing potential without a negative pregnancy test at baseline
• Patient had major surgery within 4 weeks prior to study entry, or who have not recovered from prior major surgery.
• Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
10. Known history or presence of:
• Alcohol abuse or dependence within one year prior to first drug administration;
• Drug abuse or dependence;
• Severe allergic reactions (e.g. anaphylactic reactions, angioedema)
11. History of difficulty with donating blood or difficulty in accessibility of veins.
12. Any clinically significant abnormal findings in 12 lead ECG, 2D ECHO, X-ray findings, as judged by investigator.
13. Patient is taking inhibitor, or inducer of CYP2C8 or CYP3A4 enzymes and in whom these drugs are unable to be restricted for the entire study
period.(Annexure IV)
14. Any other condition, that in the investigator’s judgment, might increase the
risk to the patient or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study.
15. Participation in any clinical study, chemotherapy and/ or radiotherapy within the past 30 days of first IMP administration or has not recovered from the side effects of previous therapy or has less than 5 washout periods from previous therapy.
- To compare and evaluate the single dose bioavailability of Paclitaxel protein-bound particles for injectable suspension(albumin-bound) 100
mg/vial of test and refernce product
- To monitor the adverse events and to ensure the safety of patients.
A total of 20 blood samples will be collected during each period. The pre-infusion
blood sample of 4.0 mL (00.00) will be collected within 5 minutes prior to the
dosing.
The post-dose blood samples of 4.0 mL each will be withdrawn.
After start of intravenous Infusion, blood samples 4.0 ml each will be collected at 0.083 (5 min), 0.167 (10 min), 0.333 (20 min), 0.417 (25 min), 0.50 (30
min), 0.580 (35 min), 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours.
Secondary Outcome
Outcome
TimePoints
To monitor the adverse events and to ensure the safety of patients.
NA
Target Sample Size
Total Sample Size="96" Sample Size from India="96" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
This is a multicenter, open label, randomized, balanced, two treatment, two period, two sequence, two way crossover, single dose, bioequivalence study of Paclitaxel protein-bound particles for injectable suspension (albumin-bound) 100 mg/vial of Cipla Ltd., India with ABRAXANE® for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) Manufactured for: Celgene Corporation Summit, USA in Breast cancer patients after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy.
Treatments will be allocated to patient by carrying out randomization using statistical techniques. During the treatment phase, each patient will receive a total of 1 dose of the reference drug and 1 dose of the test drug; patients will be randomly allocated to the sequence in which they receive study drug (i.e., reference drug then test drug or test drug then reference drug). The reference or test drug will be administered as a 30-minute intravenous infusion on Day 1 of each treatment period. Dosing in each period will be separated by at least 21 days. During each treatment period, serial blood samples will be collected at various time-points. Patients will remain in the clinical research unit till 48 hours post-dose. Pharmacokinetic sample will be collected up to 48 hours after the start of the infusion.
Total of 20 blood samples will be collected during each period. The pre-infusion blood sample of 4.0 mL (00.00) will be collected within 5 minutes prior to the dosing. The post-dose blood samples of 4.0 mL each will be withdrawn. After start of intravenous Infusion, blood samples (1 x 4.0 ml each) will be collected at 0.083 (5 min), 0.167 (10 min), 0.333 (20 min), 0.417 (25 min), 0.50 (30 min), 0.580 (35 min), 0.75 (45 min), 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 48 hours.