CTRI/2017/01/007746 [Registered on: 30/01/2017] Trial Registered Prospectively
Last Modified On:
11/08/2017
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
To compare bioavailability of Paclitaxel protein-bound particles of Cipla Ltd.,India with ABRAXANE® in Metastatic Breast cancer patients.
Scientific Title of Study
A multicenter, open label, randomized, two treatment, two period, two way crossover, single dose, bioequivalence study of paclitaxel protein-bound particles for injectable suspension (albumin-bound) 100 mg/vial by Cipla Ltd., India with ABRAXANE® for injectable suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) 100 mg/vial by Celgene Corporation, USA in breast cancer patients after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy.
Trial Acronym
CRD/09
Secondary IDs if Any
Secondary ID
Identifier
CRD/09 - Ver 01 dated 12 Aug 2016
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study) Modification(s)
Name
Dr Shailesh Bondarde
Designation
Principal Investigator
Affiliation
Address
Shatabdi Superspecialty Hospital,
Suyojit City Centre, Opp. Mahamarg Bus Stand, Mumbai Naka, Nashik
Nashik MAHARASHTRA 422005 India
Phone
9822012427
Fax
Email
shaileshbondarde@yahoo.com
Details of Contact Person Scientific Query
Name
Dr Sougat Sarkar
Designation
Medical & Safety Expert
Affiliation
Cipla Ltd.
Address
Cipla Ltd.,
Clinical Research and Development, R&D Center, 4th Floor, North Block, LBS Marg, Vikhroli West.
Mumbai MAHARASHTRA 400083 India
Phone
91-2225756449
Fax
Email
sougat.sarkar@cipla.com
Details of Contact Person Public Query
Name
Monica Razdan
Designation
Lead Project Manager
Affiliation
Cipla Ltd.
Address
Cipla Ltd.,
Clinical Research and Development, R&D Center, 4th Floor, North Block, LBS Marg, Vikhroli West.
Mumbai MAHARASHTRA 400083 India
Phone
91-2225756459
Fax
Email
monica.razdan@cipla.com
Source of Monetary or Material Support
Cipla Ltd., R&D centre, LBS Marg, Vikhroli (W), Mumbai-400 083, India.
Unique Hospital Multispecialty & Research Institute
Department of Oncology, Ground floor, OPD #2, Opp. Kiran Motor, Nr. Canal, Civil Hospital Char Rasta- Sosyo Circle Lane, Off Ring Road, Surat-395002, Gujarat, India. Surat GUJARAT
261-2636318
tanveermaksud@gmail.com
Dr Akila Balaraman
VGM Hospital and Institute of Gastroenterology
Dept. of Medical oncology, 4th Floor, Room no. 411, 2100, Trichy Road, Rajalakshmi Mills Stop, Singanallur, Coimbatore, Tamil Nadu 641005 Coimbatore TAMIL NADU
Central India Cancer Research Institute Ethics Committee
Approved
Ethics Committee Sterling Hospital
Approved
Ethics Committee, Unique Hospital Multispecialty and Research Institute
Approved
HCG – Central Ethics Committee
Approved
Institutional Ethics Committee Gleneagles Global Hospitals
Approved
Institutional Ethics Committee Meenakshi Mission Hospital & Research Centre
Approved
Institutional Ethics Committee, BGS Global Hospitals
Approved
Institutional Ethics Committee, City Cancer Centre
Approved
Institutional Ethics Committee, King George’s Medical College
Approved
Institutional Ethics Committee, Poona Medical Research Foundation
Approved
Institutional Ethics Committee, VGM Hospital
Approved
Manavata Clinical Research Institute Ethics Committee
Approved
Manipal University Ethics Committee, Kasturaba Medical College and Hospital, Mangalore
Approved
Shatabdi Hospital Ethics Committee
Approved
Sri Venkateshwara Hospital Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
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
Celgene Corporation, 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 (albumin-bound) 100 mg/vial
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) at the time of screening and capable of giving written informed consent prior to receiving any study medication.
2.Has histological or cytological confirmed metastatic breast cancer after failure of combination chemotherapy for metastatic disease 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 investigators opinion.
4.ECOG performance status of less than or equal to 2.
5.Acceptable hemopoeitic, renal and liver function.
Bone marrow function
ANC more than or equal to 1500/mm3,
Platelet count more than or equal to 100,000/mm3
Hemoglobin more than or equal to 9.0 g/dl
Renal function
Serum Creatinine less than 1.5 times ULN
Hepatic function
AST and ALT less than or equal to 2.5 times ULN
Alkaline phosphatase less than 2 times ULN
Bilirubin less than or 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 comply/adhere to the protocol requirements.
8.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 getting pregnant during the study.
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 and 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 > Grade 2 at baseline.
5.Presence of any significant physical or organ abnormality or active opportunistic infection (i.e. mycobacteria, cytomegalovirus, toxoplasma, Pneumocystis jiroveci) as determined by the Investigator.
6.Patients not completely recovered from any toxicities from previous chemo-, hormone-, immuno-, or radiotherapies less than or equal to Grade 1.
7.A positive HIV, Hepatitis B surface antigen, Hepatitis C, drugs of abuse or breath alcohol test.
8.Difficulty in fasting or consuming standard meals.
9.Patients who are:
•pregnant
•breast feeding
•of childbearing potential without a negative pregnancy test at baseline
•had major surgery within 4 weeks prior to study entry, or who have not recovered from prior major surgery
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.
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 IP administration or has less than 5 washout periods from previous therapy.
16.Patients who have not recovered from the side effects of previous therapy.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To compare and evaluate the single dose bioavailability of paclitaxel protein-bound particles for injectable suspension (albumin-bound) 100 mg/vial of test and reference product.
Pre-dose sample (within 5 mins prior to dosing), post-dose blood samples - after start of intravenous infusion, 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), 0.750 (45 min), 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 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="46" Sample Size from India="46" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
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 the patients as per the pre-defined randomization sequence (i.e., reference drug then test drug or test drug then reference drug). During the treatment phase, each patient will receive a total of 1 dose of the reference product and 1 dose of the test product. The reference or test products 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 pre-determined 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