CTRI/2023/11/059593 [Registered on: 06/11/2023] Trial Registered Prospectively
Last Modified On:
21/05/2024
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Other
Public Title of Study
Bioequivalence Study of Paclitaxel Protein-bound
Particles for Injectable Suspension (Albumin-Bound) of Qilu Pharmaceutical (Hainan) Co., Ltd., China in Patients with Breast Cancer
Scientific Title of Study
A Randomized, Open-Label, Two Period, Two-Treatment, Two Sequence, Single Dose, Crossover, Bioequivalence Study of Paclitaxel Protein-bound Particles for Injectable Suspension (Albumin-Bound) of Qilu Pharmaceutical (Hainan) Co., Ltd., China with ABRAXANE® (Paclitaxel Protein-bound Particles for Injectable Suspension) (albumin-bound) manufactured for Celgene Corporation, Summit, NJ 07901 in Patients with Breast Cancer.
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
Protocol No.: C2A02989 Version: 02 Date: 15 Jun 2023
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Dharmesh Domadia
Designation
Vice President Global Clinical Operation
Affiliation
Cliantha Research limited
Address
Cliantha Corporate, TP 86, FP 28/1, Off S.P. Ring Road, Sarkhej, Ahmedabad - 382 210, Gujarat, India
Ahmadabad GUJARAT 382210 India
Phone
9879590828
Fax
Email
ddomadia@cliantha.com
Details of Contact Person Scientific Query
Name
Dr Ankesh Barnwal
Designation
Associate Director- II– Clinical Trial Medical Services
Affiliation
Cliantha Research limited
Address
Cliantha Corporate, TP 86, FP 28/1, Off S.P. Ring Road, Sarkhej, Ahmedabad - 382 210, Gujarat, India
Ahmadabad GUJARAT 382210 India
Phone
07966219500
Fax
Email
abarnwal@cliantha.com
Details of Contact Person Public Query
Name
Mr Devesh Verma
Designation
Associate Director-I - Clinical Trials
Affiliation
Cliantha Research limited
Address
Cliantha Corporate, TP 86, FP 28/1, Off S.P. Ring Road, Sarkhej, Ahmedabad - 382 210, Gujarat, India
Ahmadabad GUJARAT 382210 India
Phone
9712908404
Fax
Email
dverma@cliantha.com
Source of Monetary or Material Support
Qilu Pharmaceutical (Hainan) Co., Ltd.
No.273-A, Nanhai Avenue, National High-Tech Zone, Haikou, 570314, China (CHN) Tel 86-531-83126901
Primary Sponsor
Name
Qilu Pharmaceutical (Hainan) Co., Ltd.
Address
No.273-A, Nanhai Avenue, National High-Tech Zone, Haikou, 570314, China (CHN)
Tel 86-531-83126901
Consulting Room No.4, Clinical Research Department, Ground Floor, Beside IOCL Petrol Pump, Near Gorwa ITI, Vadodara, Gujarat -390016, India Vadodara GUJARAT
8780466776
amhctbaroda@gmail.com
Dr K Velavan
Erode Cancer Centre
Department of radiation Oncology, CRD Ground floor, new building, 1/393, Velavan Nagar, Near Chintamani Petrol Bunk, Perundurai Road, Thindal Medu, Thindal Erode-638012, Tamil Nadu, India Erode TAMIL NADU
9842334222
kvels@rediffmail.com
Dr Patel Akash Dineshbhai
HCC Happiness Care and Cure Multispecialty Hospital LLP
HCC Happiness Care and Cure Multispecialty Hospital LLP, 302, 303, 305, and 407, Sheetal Varsha Mall-5, Shivranjani Cross Road, Satellite, Ahmedabad - 380015, Gujarat, India Ahmadabad GUJARAT
9601987566
drakash.cr@gmail.com
Dr Rajnish Nagarkar
HCG Manavata Cancer Centre
Clinical Research Department, 1st floor, MCRI new building, Behind Shivang Auto, Mumbai Naka, Nashik-422002, Maharashtra, India Nashik MAHARASHTRA
9823061929
drraj@manavtacancercentre.com
Dr Maheshkumar Kalloli
KLES Dr. Prabhakar Kore Hospital & MRC
OPD No-37A, Third Floor, KLES Dr Prabhakar Kore Hospital & Medical Research Centre, Clinical Research Department, 2nd Floor, Nehrunagar Belagavi -590010, Karnataka, India Belgaum KARNATAKA
9591242900
mahesh.kalloli@gmail.com
Dr Suraj Pawar
Kolhapur Cancer Centre Pvt Ltd
3rd floor Clinical Research Department, A/P R.S No. 238, Opp. Mayur Petrol Pump, Gokul Shirgaon, Maharashtra -416234, India Kolhapur MAHARASHTRA
9822014908
surajpawar2001@yahoo.co.in
Dr Murali Subramanian
Medstar Multispeciality Hospital
Clinical Research Department, Second floor, 641/17/1/3, Kodigehalli Main Road, Sahakarnagar, Bangalore-560092, Karnataka, India Bangalore KARNATAKA
9945813327
medstarclinicalresearch@gmail.com
Dr Parimkayala Radhika
MNJ Institute of Oncology & Regional Cancer Centre
Old Building, 3rd Floor, Clinical Trial Room No.11, Clinical Research Department , Red Hills, Hyderabad-500004, Telangana, India Hyderabad TELANGANA
9848792682
radhika.parimkayala@gmail.com
Dr Anilkumar MR
Oncoville Cancer Hospital and Research Centre
Clinical Research Department, 4th Floor,No 4, 80 ft. road, 7th Block, Nagarabhavi, 2nd Stage, Bangalore- 560072, Karnataka, India Bangalore KARNATAKA
9739808502
dranil.onco@gmail.com
Dr Lokesh K N
Radhakrishna Multispeciality Hospital and IVF Center
Clinical Research Department, 4th floor, 3/4 Sunrise Tower, JP road, Girinagar , Bangalore, Karnataka 560085, India Bangalore KARNATAKA
8971609070
drlokeshkn.rmh@gmail.com
Dr Reshma Puranik
Saikrupa Hospital
Clinical Research Department, 3rd floor, Renuka Corner, Tapkir chowk, Thergaon, Pune- 411033, Maharashtra, India Pune MAHARASHTRA
9552544910
reshma.puranik@gmail.com
Dr Rakesh Kumar Mishra
Sanjeevani CBCC USA Cancer Hospital
Clinical Research Department 1st floor Admin Building, Dawada Colony, Near Pachpedi Naka, Raipur-492001, Chhattisgarh, India Raipur CHHATTISGARH
9101202963
mishra.rakesh0101@gmail.com
Dr Nirali Trivedi
Shankus Hospitals Pvt.Ltd
Oncology Department, Shankus Hospitals Pvt.Ltd. B/H Divine Child School, Near Shankus Water Park, Ahmedabad-Mehsana Highway, Baliyasan, Mehsana, Gujarat-382732 Mahesana GUJARAT
8980008109
niralibaxi81@yahoo.com
Dr V Arumugam
Tirunelveli Government Medical College & Hospital
Clinical Research Department, 1st floor Oncology wing, North High Ground Road, Palayamkottai, Tirunelveli, Tamil Nadu- 627011, India Tirunelveli TAMIL NADU
Institutional Ethics Committee Erode Cancer Centre
Approved
Institutional Ethics committee of OCH and RC
Approved
KCC Institutional Ethics Committee
Approved
Manavata Clinical Research Institute Ethics Committee
Approved
Medstar Speciality Hospital Ethics Committee
Approved
MNJIORCC Ethics Committee
Submittted/Under Review
Parth Hospital Ethics Committee
Approved
Saikrupa Hospital Institutional Ethics Committee
Approved
Sanjeevani Cancer 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: C50||Malignant neoplasm of breast,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
ABRAXANE® (Paclitaxel Protein-bound Particles for Injectable Suspension) (albumin-bound)
Each eligible patient will be administered a single intravenous infusion (260 mg/m2) of the reference product
Intervention
Paclitaxel protein-bound particles (albuminbound), 100 mg per vial
Each eligible patient will be administered a single intravenous infusion (260 mg/m2) of the test product
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Female
Details
Inclusion criteria:
Patient will be eligible for inclusion in this study only if all of the following criteria apply:
1. Female patient of 18 to 65 years of age (both inclusive).
2. Breast cancer with one of the following:
a. Has histological or cytological confirmed metastatic breast cancer after failure of combination chemotherapy for metastatic disease.
b. Has had a relapse within 6 months of adjuvant chemotherapy.
c. Has histological or cytological confirmed breast cancer who is a candidate for albumin bound paclitaxel therapy in accordance with the standard of care (NCCN guidelines- Breast Cancer) as per PI judgement.
Note: In the case of items a and b above, prior therapy should have included an anthracycline, such as doxorubicin, daunorubicin, mitoxantrone or other related compounds unless clinically contraindicated.
3. Adequate hematological, renal, and hepatic function as defined by the following screening laboratory values obtained at screening and prior to randomization (patients should not have received a transfusion within 7 days before the screening laboratory assessments):
a. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3 (1.5x109/L)
b. Platelet count ≥ 100,000 cells/mm3 (100x109/L)
c. Hemoglobin ≥ 9 g/dL
d. Creatinine clearance > 60 mL per minute (using Cockcroft-Gault formula)
Formula of creatinine clearance: Crcl equals to (140 − age) × body weight (Kilogram weight)/plasma creatinine (mg/dl) × 72 x 0.85 (considering female patients).
Total bilirubin ≤ 1.5 x ULN (Upper Limit of Normal)
e. AST (SGOT) ≤ 2.5 x ULN
f. ALT (SGPT) ≤ 2.5 x ULN
g. Serum albumin ≥ 3.0 gm/dL
h. Alkaline phosphatase < 2.5 x ULN
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
5. All other clinical laboratory parameters and ECG findings deemed normal or not clinically significant judged by the Investigator.
6. Body surface area (BSA) that is within 1.2 to 2.2 m2, calculated using the Du Bois Formula.
7. Patient with life expectancy of at least 3 months at the time of enrollment.
8. Female patient with postmenopausal status or female patient of childbearing
potential with negative pregnancy test [negative serum pregnancy test (β-hCG) at screening, and negative urine pregnancy test prior to each dose of study drug] must agree to practice an acceptable method of contraception throughout the study period and for at least 6 months after last dose of study drug. No history of pregnancy in last 30 days prior to randomization.
Women who are not postmenopausal ≥ 52 weeks or surgically sterilized (e.g., hysterectomy, bilateral oophorectomy, bilateral tuballigation) prior to screening are considered of child-bearing potential.
9. Patient who had taken COVID-19 vaccine, must have recovered from vaccine related adverse events before being screened for the study.
10. Patient willing to provide written informed consent and able to adhere to all protocol requirements and study procedures throughout the study.
11. Ability to comprehend and be informed of the nature of the study, as assessed by study clinic staff.
ExclusionCriteria
Details
Exclusion Criteria:
Patient will not be eligible for inclusion in this study if any of the
following criteria apply:
1. History of allergy or hypersensitivity reactions to a paclitaxel or the components of paclitaxel protein-bound particles for injectable suspension (albumin-bound) including, albumin and PEG 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 breast cancer unless determined as not clinically significant by the Investigator.
3. Patient with presence of uncontrolled hypertension or diabetes mellitus.
4. History of any other malignancy within the last 5 years.
5. Ongoing or planned lactation during study period.
6. Acute active infection requiring treatment from screening till randomization.
7. Receipt of other taxane product within the 30 days prior to randomization.
8. The patient receives treatment with any:
a. Hormonal therapy 2 weeks prior to first dose
b. Chemotherapy (except for palliative bisphosphonate therapy for bone pain which can be administered as clinically indicated) 4 weeks prior to first dose
c. Investigational drug or immunotherapy within 4 weeks prior to first dose
d. Concurrent radiation therapy (except for palliative radiotherapy for bone pain which can be administered as clinically indicated)
9. Incomplete recovery from any toxicities from previous chemotherapy, hormone therapy, immunotherapy, or radiotherapies Grade 1 or higher by current version of CTCAE, with the exception of alopecia.
10. Patient with preexisting peripheral neuropathy of NCI toxicity scale >2.
11. Major surgery within 30 days prior to randomization, or incomplete recovery from prior major surgery.
12. Known history or presence of any clinically significant disease or condition other than cancer unless determined as not clinically significant by the Investigator.
13. Known history or presence of:
a. Infection with Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C
b. Alcohol or drug abuse or dependence within one year prior to randomization
14. Patient with known CNS metastasis.
15. Participation in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or the use of investigational devices with therapeutic intent within 30 days or period equivalent of 5 half-lives of the investigational intervention prior to randomization.
16. Receipt of any known CYP2C8 and CYP3A4 inhibitor (e.g.ketoconazole and other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir, saquinavir, indinavir, and nelfinavir) or inducer (e.g., rifampicin, carbamazepine, phenytoin, efavirenz, and nevirapine) 14 days before randomization.
17. Patient having signs and symptoms suggestive of COVID-19 (such as fever, dry cough, difficulty in breathing and fatigue).
18. Consumption of any grapefruit, star fruit, grape fruit juice, Seville oranges, and seville orange juice and its products within 07 days prior to randomization.
19. Ingestion of any alcoholic food (e.g. plum pudding, cake, chocolate containing alcohol) or beverage containing alcohol or utilize recreational drugs, caffeine or xanthine containing food or beverage within the 48 hours prior to randomization.
20. Donation or loss of blood or plasma of one unit (about 450 mL whole blood or 220 mL plasma) in the previous 90 days prior to randomization.
21. History of difficulty with donating blood or difficulty in accessibility of veins or intolerance to venipuncture.
22. Any food allergy, intolerance, restriction or special diet that, in the opinion of the Investigator, could contraindicate the patient’s participation in this study.
23. 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.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Not Applicable
Primary Outcome
Outcome
TimePoints
Cmax, AUCt, AUCi
Considering the minimum washout period, expected study duration of clinical part is 9 week from the day of screening
Secondary Outcome
Outcome
TimePoints
Tmax, Kel, AUC_%Ext rap_obs and tHalf
Considering the minimum washout period, expected study duration of clinical part is 9 week from the day of screening
Target Sample Size
Total Sample Size="60" Sample Size from India="60" Final Enrollment numbers achieved (Total)= "60" Final Enrollment numbers achieved (India)="60"
Phase of Trial
N/A
Date of First Enrollment (India)
15/11/2023
Date of Study Completion (India)
11/09/2024
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Date Missing
Estimated Duration of Trial
Years="1" Months="4" Days="21"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Completed
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
Objective:
Primary Objective:
To evaluate the bioequivalence of test product paclitaxel protein-bound particles for injectable suspension (albumin-bound), for intravenous use (manufactured by: Qilu Pharmaceutical (Hainan) Co., Ltd., China) with reference product ABRAXANE® (Paclitaxel Protein-bound Particles for Injectable Suspension) (albumin-bound) manufactured for Celgene Corporation, Summit, NJ 07901 in patients with breast cancer.
Secondary Objective:
To monitor safety of the patients.
Study Population:
Approx. 60 patients with breast cancer need to be enrolled.
Test Product (T)
Paclitaxel protein-bound particles for injectable suspension (albumin bound), 100 mg per vial, for intravenous use manufactured by Qilu Pharmaceutical (Hainan) Co., Ltd., China.
Reference Product (R)
ABRAXANE® (Paclitaxel Protein-bound Particles for Injectable Suspension) (albumin-bound), for intravenous use manufactured for Celgene Corporation, Summit, NJ 07901.
Endpoints
Pharmacokinetic Endpoints:
Primary Endpoint(s)
Cmax, AUCt, AUCi
Secondary Endpoint(s)
Tmax, Kel, AUC_%Ext rap_obs and tHalf
Safety Endpoints:
Incidence of Treatment-Emergent Adverse Events (TEAEs) and serious adverse events (SAE).
Housing:
All patients will be housed in the study site from at least 12 hours before administration of the IP in both periods and will continue to remain in the clinical facility for at least 24 hours after administration of IP in both periods. All PK samples thereafter (48, 72 and 96 hrs) will be collected on ambulatory basis in each period.
Note: In addition to above requirement, the patient may be housed in the clinical facility (hospital) for the appropriate duration during the study if, in the opinion of the Investigator, it is necessary for the clinical management of the patient.
Clinical Evaluations :
Patient will have to come to site/clinic for the following visits during the study:
Visit 1: Screening Visit (within 21 days prior to first dosing)
Visit 2: Check-in Period-I; Day -1: (At least 12 hours prior to dosing)
(Note: Check-out of Period-I will be on Day 2)
Visit 3: Period-I; Day 3: Ambulatory visit
Visit 4: Period-I; Day 4: Ambulatory visit
Visit 5: Period-I; Day 5: Ambulatory visit
Visit 6: Period-I; Day 14: Ambulatory visit
ï‚· A minimum gap of 21 days will be kept between administrations of the two doses.
Visit 7: Check-in Period-II; Day -1: (At least 12 hours prior to dosing)
(Note: Check-out of Period-II will be on Day 2)
Visit 8: Period-II; Day 3: Ambulatory visit
Visit 9: Period-II; Day 4: Ambulatory visit
Visit 10: Period-II; Day 5: Ambulatory visit
Visit 11: End of study/Safety follow-up (14 ± 2 days after last dose of study drug)
Screening period (within 21 days prior to first dosing on Day 1): After signing the informed consent form, the patients will be screened for confirming the eligibility for study participation. Patients’ satisfying all the inclusion and the exclusion criteria will be considered eligible for the study. All the screening assessments will be performed within 21 days prior to first dosing on Day 1.
Treatment Period: During the Check-in visit for Period-I, inclusion and exclusion criteria will be reviewed. Eligible patients will be housed in the clinical facility on Day -1 of both periods (Period-I and Period-II). Patients will randomly receive test product or reference product on Day 1 as per randomization schedule.
Dosing will be initiated at 1 hour after providing the breakfast. Upon randomization, each eligible patient will receive two courses of treatment (test and reference), which includes two intravenous (IV) infusions of assigned study drug at a dose of 260 mg/m2 [i.e. First infusion on Day 1 of Period-I and second infusion on Day 1 of Period-II]. After completion of infusion on Day 1 of Period-I and Period-II the patient will be housed in the clinical facility for 24 hours. Later, the patient will have to visit clinical facility for PK sample collection on Day 3, Day 4 and Day 5 of each period. There will be a washout period (drug free period) for minimum 21 days between two consecutive periods.
End of study/safety follow-up: Patient will have to visit the clinical facility for safety follow-up on 14±2 days after last dose of study drug.