Bioequivalence Study of Paclitaxel Protein-boundParticles for Injectable Suspension (Albumin-Bound) of Qilu Pharmaceutical (Hainan) Co., Ltd., China in Patients with Breast Cancer

Completed

• Conditions: Malignant neoplasm of breast,

• Registration Number: CTRI/2023/11/059593
• Lead Sponsor: Qilu Pharmaceutical (Hainan) Co., Ltd.

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-11-15
• Last Update Posted: 2024-05-21
• Study Completion: 2024-11-09

Recruitment & Eligibility

• Status: Completed
• Sex: Female
• Target Recruitment: 60

Inclusion Criteria

• 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).
• Breast cancer with one of the following: a.
• Has histological or cytological confirmed metastatic breast cancer after failure of combination chemotherapy for metastatic disease.
• Has had a relapse within 6 months of adjuvant chemotherapy.
• 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.
• 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.
• Body surface area (BSA) that is within 1.2 to 2.2 m2, calculated using the Du Bois Formula.
• Patient with life expectancy of at least 3 months at the time of enrollment.
• 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.
• Patient who had taken COVID-19 vaccine, must have recovered from vaccine related adverse events before being screened for the study.
• Patient willing to provide written informed consent and able to adhere to all protocol requirements and study procedures throughout the study.
• Ability to comprehend and be informed of the nature of the study, as assessed by study clinic staff.

Exclusion Criteria

• 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.
• 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.
• Patient with presence of uncontrolled hypertension or diabetes mellitus.
• History of any other malignancy within the last 5 years.
• Ongoing or planned lactation during study period.
• Acute active infection requiring treatment from screening till randomization.
• Receipt of other taxane product within the 30 days prior to randomization.
• 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.
• Patient with preexisting peripheral neuropathy of NCI toxicity scale >2.
• Major surgery within 30 days prior to randomization, or incomplete recovery from prior major surgery.
• Known history or presence of any clinically significant disease or condition other than cancer unless determined as not clinically significant by the Investigator.
• Known history or presence of: a.
• Alcohol or drug abuse or dependence within one year prior to randomization 14.
• Patient with known CNS metastasis.
• 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.
• 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.
• Patient having signs and symptoms suggestive of COVID-19 (such as fever, dry cough, difficulty in breathing and fatigue).
• Consumption of any grapefruit, star fruit, grape fruit juice, Seville oranges, and seville orange juice and its products within 07 days prior to randomization.
• 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.
• 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.
• History of difficulty with donating blood or difficulty in accessibility of veins or intolerance to venipuncture.
• Any food allergy, intolerance, restriction or special diet that, in the opinion of the Investigator, could contraindicate the patient’s participation in this study.
• 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.

Study & Design

• Study Type: BA/BE
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Cmax, AUCt, AUCi	Considering the minimum washout period, expected study duration of clinical part is 9 week from the day of screening

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (14)

Anand Multispeciality Hospital; 🇮🇳 Vadodara, GUJARAT, India

Erode Cancer Centre; 🇮🇳 Erode, TAMIL NADU, India

HCC Happiness Care and Cure Multispecialty Hospital LLP; 🇮🇳 Ahmadabad, GUJARAT, India

HCG Manavata Cancer Centre; 🇮🇳 Nashik, MAHARASHTRA, India

KLES Dr. Prabhakar Kore Hospital & MRC; 🇮🇳 Belgaum, KARNATAKA, India

Kolhapur Cancer Centre Pvt Ltd; 🇮🇳 Kolhapur, MAHARASHTRA, India

Medstar Multispeciality Hospital; 🇮🇳 Bangalore, KARNATAKA, India

MNJ Institute of Oncology & Regional Cancer Centre; 🇮🇳 Hyderabad, TELANGANA, India

Oncoville Cancer Hospital and Research Centre; 🇮🇳 Bangalore, KARNATAKA, India

Radhakrishna Multispeciality Hospital and IVF Center; 🇮🇳 Bangalore, KARNATAKA, India

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Anand Multispeciality Hospital

🇮🇳Vadodara, GUJARAT, India

Dr Nirajkumar Navinchandra Bhatt

Principal investigator

8780466776

amhctbaroda@gmail.com