bioequivalence study with pharmacokinetic endpoints of Paclitaxel Protein-Bound Particles for Injectable Suspension.
Scientific Title of Study
A randomized, open label, balanced, multicenter, two-treatment, two-period, two-sequence, two-way crossover, single dose, bioequivalence study with pharmacokinetic endpoints of Paclitaxel Protein-Bound Particles for Injectable Suspension (albumin-bound) 100 mg/vial at a dose of 260 mg/m2 with ABRAXANE® for Injectable Suspension (albumin--bound) 100 mg/vial at a dose of 260 mg/m2 in Breast cancer subjects after failure of combination chemotherapy for metastatic disease.
Trial Acronym
NA
Secondary IDs if Any
Secondary ID
Identifier
NA
NIL
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Institutional Ethics Committee –Kailash Cancer Hospital & Research Cetre
Approved
Institutional Ethics Committee Erode Cancer Centre
Approved
Institutional Ethics Committee for Human Research
Submittted/Under Review
Institutional Ethics Committee HCG Cancer Centre
Approved
Institutional Ethics Committee HCG Curie City Cancer Centre
Approved
Institutional Ethics Committee, KLE University
Approved
Manavata Clinical Research Institute Professional Ethics Committee
Approved
MNJIORCC Ethics Committee
Approved
Noble Hospital Institutional Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C509||Malignant neoplasm of breast of unspecified site,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
ABRAXANE® (Paclitaxel Albumin-Bound)
ABRAXANE® for Injectable Suspension (albumin--bound) 100 mg/vial at a dose of 260 mg/m2 as intravenous infusion over 30 minutes (±5 minutes) of Celgene Corporation, Summit, NJ 07901
Intervention
Paclitaxel (Albumin-Bound)
Paclitaxel Protein-Bound Particles for Injectable Suspension (albumin-bound) 100 mg/vial at a dose of 260 mg/m2 as intravenous infusion over 30 minutes (±5 minutes) of Ningbo Shouzheng Medicinal Research Co., Ltd
Female subjects will be considered eligible for the study based on the following criteria:
1. Willing and able to provide voluntary informed consent and to follow the protocol requirements.
2. Females aged 18 to 65 years (both inclusive) having Body Mass Index BMI at least 17.00 calculated as weight in kg per height in m2.
3. Subjects with histopathologically or cytologically confirmed breast cancer
4. Subjects with breast cancer after failure of combination chemotherapy for metastatic disease or having relapse within 6 months of adjuvant chemotherapy. (Prior therapy should have included an anthracycline unless clinically contraindicated)
5. Eastern Cooperative Oncology Group (ECOG) performance status Less or equal to 2.
6. Life expectancy of at least 3 months at the time of enrolment.
7. Acceptable hematology status:
a. Hemoglobin greater or equal to 9.0 g per dL
b. Absolute neutrophil count ANC greater or equal to 1500 cells per mm3
c. Platelet count greater or equal to 1, 00,000 cells per mm3
8. Acceptable liver function:
a. Alanine aminotransferase ALT Less or equal to 2.5 X ULN
b. Aspartate aminotransferase AST Less or equal to 2.5 X ULN
c. Bilirubin less or equal to 1.5 X ULN
d. Alkaline phosphatase less or equal to 5 X ULN
9. Subjects with Creatinine clearance greater or equal to 60 mL per minute
10. Subjects with negative serum pregnancy test at screening and negative urine pregnancy test at Day 0.
11. Women of child bearing potential (defined as women physiologically capable of becoming pregnant, unless they are using effective method of contraception during dosing of the investigational product) practicing acceptable methods of contraception. Acceptable methods of contraception are
a. Hormonal method (including oral, vaginal ring, transdermal patch, implanted or injection) started at least 7 days prior to day 0 plus one barrier method (cervical cap, diaphragm, contraceptive sponge, vaginal spermicide, female or male condom
b. Intrauterine device IUD or intrauterine system IUD or IUS placed 7 days prior to day 0
c. Two barrier method used together (cervical cap, diaphragm, contraceptive sponge, vaginal spermicide, male or female condom)
d. Male sterilization at least 6 months prior to the screening, should be the sole male partner for that subject) plus one additional contraception method (hormonal or barrier method)
e. Documented tubal sterilization (tubal ligation or transcervical tubal occlusion with documentation of occlusion 6 months post-procedure)
f. Total abstinence, partial abstinence is not acceptable (no sexual intercourse or genital contact with a male partner)
12. Female subjects of non-child bearing potential or female subjects who have completed menopause are defined as subjects who have 12 consecutive months of spontaneous amenorrhea (not amenorrhea induced by a medical condition or medical therapy) or have bilateral absence of the ovaries. Female subjects of non-child bearing potential are not required to use effective method of contraception during the study
13. No history of addiction to any recreational drug or drug dependence or alcohol addiction
ExclusionCriteria
Details
Female subjects will be excluded from the study based on the following criteria:
1.Known hypersensitivity to Paclitaxel or the components of Paclitaxel Protein-Bound Particles for Injectable Suspension (albumin--bound) or to any of the related drugs (other taxane products).
2.History or presence of any uncontrolled systemic disease (e.g. cardiovascular disease, hypertension, diabetes mellitus etc.).
3.Subjects taking any of the inhibitors or inducers of either CYP2C8 or CYP3A4. (Appendix C)
4.Known CNS metastasis.
5.Major surgical procedure (including periodontal) within 28 days of first dose of Investigational Product.
6.Surgical or other non-healing wounds.
7.Subjects with positive serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV).
8.Subjects with current clinical or laboratory evidence of active infection.
9.History of other malignancies in the last 5 years (except in situ cancer or basal or squamous cell skin cancer).
10.Has not recovered to Grade 0 or 1 toxicity from previous anticancer treatments or previous investigational agents. Exceptions are alopecia (any grade is acceptable), fatigue (Grade less than or equal to is acceptable), and peripheral neuropathy (stable Grade 2 is acceptable) (Per National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], V5.0).
11.Participation in any clinical study within 90 days before the first dose of Investigational Product.
12.Loss of greater or equal to 350mL (1 unit) of blood within 90 days of enrollment in the study.
13.Any other medical condition or serious intercurrent illness that, in the opinion of the Investigator, may make it undesirable for the subject to participate in the study including but not limited to cirrhosis or psychiatric illness/social situations that would limit adherence to study requirements.
14.Subjects who are breastfeeding and lactating.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To assess the bioequivalence by comparing PK parameters of Paclitaxel Protein-Bound Particles for Injectable Suspension (albumin-bound) 100 mg/vial at a dose of 260 mg/m2 with ABRAXANE® for Injectable Suspension (albumin--bound) 100 mg/vial at a dose of 260 mg/m2 in Breast cancer subjects after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy under fasting condition
Day 1 and 22, 2 and 23, 3 and 24, 4 and 25, 5 and 26.
To monitor the adverse events and to assess the safety and tolerability in subjects.
Day 1 and 22, 2 and 23, 3 and 24, 4 and 25, 5 and 26.
Safety Assessment on Day 7 & 14 , Day 28 & 35.
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"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This a randomized, open label, balanced, multicenter,
two-treatment, two-period, two-sequence, two-way crossover, single dose,
bioequivalence study with pharmacokinetic endpoints of Paclitaxel Protein-Bound
Particles for Injectable Suspension (albumin-bound)100mg/vialat a dose of 260mg/m2of Ningbo
Shouzheng Medicinal Research Co., Ltd. with ABRAXANE® for Injectable
Suspension (albumin--bound)100mg/vial at a
dose of 260 mg/m2 of Celgene Corporation, Summit, NJ 07901 in Breast
cancer subjects after failure of combination chemotherapy for metastatic
disease or relapse within 6 months of adjuvant chemotherapy under fasting
condition
The Primary Objective is To assess the bioequivalence by
comparing PK parameters of Paclitaxel Protein-Bound Particles for Injectable
Suspension (albumin-bound) 100mg/vial at a dose of 260mg/m2 of Ningbo Shouzheng Medicinal Research
Co., Ltd. with ABRAXANE® for Injectable Suspension (albumin--bound)100mg/vial at a dose of 260 mg/m2of Celgene Corporation, Summit, NJ 07901 in Breast cancer
subjects after failure of combination chemotherapy for metastatic disease or
relapse within 6 months of adjuvant chemotherapy under fasting condition
Upon
randomization, subjects will receive assigned study drug on Day 1 (Period 01)
and Day 22 (Period 02) based on the randomization schedule (either Test (A) or
Reference (B)) at a dose of 260mg/m2 intravenously over 30minutes
under fasting conditions.
Statistical analysis will be
performed on the pharmacokinetic parameters using SAS® statistical
software. The 90% confidence interval
of the relative mean (Geometric mean) of the test to reference formulation for
Ln-transformed Cmax, AUC0-t and AUC0-inf
should be within 80.00% to 125.00% for unbound and total paclitaxel to
establish bioequivalence.