Bioequivalence study of Paclitaxel protein-bound particles for injectable 100 mg/vial of Cipla Ltd.,India with ABRAXANE® for Injectable Manufacturedfor: Celgene Corporation Summit, USA in Metastatic Breast cancer patients after failure of Chemotherapy /relapse after prior Chemotherapy.
- Conditions
- Breast cancer patients after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy.
- Registration Number
- CTRI/2015/09/006156
- Lead Sponsor
- Cipla Ltd India
- 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 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 The post-dose blood samples of 4.0 mL each will be withdrawn.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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- Female
- Target Recruitment
- 96
- Female patients, 18 to 65 years of age (both inclusive).
- 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.).
- Patients with life expectancy of at least 3 months as per the investigator opinion.
- ECOG performance status of less and equal to 2.
- 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.
- Availability for the entire study duration and willingness to adhere to the protocol requirements.
- 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.
- 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.
- 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.
- History of any other malignancy within the last 5 years which could affect the diagnosis or assessment of breast cancer.
- Sensory / Peripheral neuropathy of more than Grade 2 at baseline.
- Presence of any significant physical or organ abnormality or active opportunistic infection (i.e. mycobacteria, cytomegalovirus, toxoplasma, Pneumocystis carinii) as determined by the Investigator.
- Patients not completely recovered from any toxicities from previous chemotherapy, hormonetherapy, immunotherapy, or radiotherapies less than or equal to Grade 1.
- A positive test result for any of the following: HIV, Hepatitis B surface antigen, Hepatitis C, drugs of abuse and breath alcohol test.
- Difficulty fasting or consuming standard meals.
- 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.
- Any clinically significant abnormal findings in 12 lead ECG, 2D ECHO, X-ray findings, as judged by investigator.
- 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.
- 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.
Study & Design
- Study Type
- BA/BE
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method mg/vial of test and refernce product 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. - To compare and evaluate the single dose bioavailability of Paclitaxel protein-bound particles for injectable suspension(albumin-bound) 100 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. - 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 Measures
Name Time Method To monitor the adverse events and to ensure the safety of patients. NA
Trial Locations
- Locations (21)
Acharya Tulsi Regional Cancer Treatment & Research Institute
🇮🇳Bikaner, RAJASTHAN, India
Aster Aadhar Hospital
🇮🇳Kolhapur, MAHARASHTRA, India
City Cancer Centre
🇮🇳Krishna, ANDHRA PRADESH, India
Dr. GVN Cancer Institute
🇮🇳Tiruchirappalli, TAMIL NADU, India
Erode Cancer Centre
🇮🇳Erode, TAMIL NADU, India
Government Medical College
🇮🇳Nagpur, MAHARASHTRA, India
King George Medical College
🇮🇳Lucknow, UTTAR PRADESH, India
KLES Dr. Prabhakar Kore Hospital & MRC
🇮🇳Belgaum, KARNATAKA, India
Kolhapur Cancer Centre
🇮🇳Kolhapur, MAHARASHTRA, India
Mangal Anand Hospital
🇮🇳Mumbai, MAHARASHTRA, India
Scroll for more (11 remaining)Acharya Tulsi Regional Cancer Treatment & Research Institute🇮🇳Bikaner, RAJASTHAN, IndiaDr Neeti SharmaPrincipal investigator9782300231shekhar@siaramresearch.com