A Clinical Trial of two drugs Paclitaxel (Test) and Abraxane® (Reference) to study the pharmacokinetics and safety in patients with metastatic breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy

Not yet recruiting

• Conditions: Malignant neoplasm of breast of unspecified site,

• Registration Number: CTRI/2025/05/086951
• Lead Sponsor: Amneal EU Limited

Brief Summary

This is a multicenter, open label, randomized, single dose, two-treatment, two-period, two-sequence, crossover, bioequivalence study with pharmacokinetic endpoint.

There will be a screening period up to 14 days. If the patient passes all the screening criteria, PI can immediately enroll the patient and can consider that day as Day -1.

This will be a two-period study. Period 1 dosing will be on Day 1 and Period 2 dosing will be on Day 22.

There will be 11 patient visits to the study site; Visit 1-Screening (Day -14 to -1), Visit 2-Day -1, Visit 3- Day 5, Visit 4-Day 6, Visit 5- Day 7, Visit 6-Day 14, Visit 7- Day 21, Visit 8-Day 26, Visit 9- Day 27, Visit 10- Day 28 and Visit 11- Day 35 plus 2. Total duration of the study will be approximately 51 days.

All eligible patients will be advised to visit the study site on Day -1 for randomization and will be confined till Day 4 for Period 1. Patients will be requested to visit on Day 5, Day 6, and Day 7 for ambulatory sample collection. Patients will be requested to visit the study site on Day 14 for ANC sample collection and then on Day 21 for Period 2 followed by confinement till Day 25. Patients will be requested to visit on Day 26, Day 27, and Day 28 for ambulatory sample collection. Patients may be confined till last sample of collection in respective period as per investigator’s discretion considering patient condition.

Patients will be administered with any antiemetic medication within 1 hour prior to dosing on Day 1 and Day 22 to prevent nausea and vomiting.

To minimize the risk of severity of hypersensitivity reactions, patients will receive Dexamethasone 20 mg intravenously within 45 minutes prior to the dose on Day 1 and Day 22 as per the institution or investigator’s discretion.

Pre-medications can be administered as per the institution or investigator’s discretion, and it should be same in both periods of the study.

After fasting of at least 10 hours, patients will be dosed with Paclitaxel suspension for injection (either Test or Reference product as per randomization schedule) as an intravenous infusion at a dose 260 mg per m2 over 30 minutes plus 5 minutes in each period i.e., on Day 1 (Period 1) and Day 22 (Period 2) by Study Nurse and or or Investigator.

If the patient’s health status prevents fasting, then a non-high-fat diet will be provided for both study periods under same conditions during the study.

If the patient’s health status necessitates a dose reduction or any change in the recommended 260 mg per m2 dose administered in 30 minutes, such patient’s will be withdrawn from the study.

On Day 1 and Day 22, complete PK sampling will be performed. Venous blood samples (approximately 3 mL) will be withdrawn at 0.00 (prior to infusion), and 0.08, 0.17, 0.25, 0.33, 0.42 (during infusion), 0.50 (i.e., immediately at the end of the infusion [a window period of  plus 2 minutes will be allowed]), 0.67, 0.75, 1.00, 1.25, 1.50, 2.00, 3.00, 4.00, 6.00, 8.00, 12.00, 24.00, 48.00, 72.00, 96.00, 120.00 and 144.00 hours after the start of the infusion (24 samples, 72 mL of blood and 9.5 mL heparinized blood in each period). Pre dose sample will be obtained within 30 minutes before dosing, sample collection during infusion and post end of infusion, a window period of plus minus 2 minutes is allowed during inhouse sample collection and plus minus 2 hours for ambulatory sample collection.

The blood will be collected in Na Heparin vacutainers tubes.

Blood loss for safety assessments at Screening, Randomization and End of Study Visits will be 45 mL (15 mL each), 144 mL for PK samples, 3 mL for ANC (Absolute neutrophil count) testing on Day 14, 19 mL heparinized blood, and 6 mL (3 mL each) for Hematology and LFT on Day 21. Total blood loss during the study will be 217 mL.

Patients will be requested to visit the site on Day 35 plus 2 days for end of study evaluation.

Study medication administration, blood sample collection, processing and analysis should be done under yellow monochromatic light.

Detailed Description

Not available

Study Timeline

• Study Start: 2025-06-17
• Last Update Posted: 2025-06-17

Recruitment & Eligibility

• Status: Not Yet Recruiting
• Sex: Female
• Target Recruitment: 60

Inclusion Criteria

• Signed informed consent obtained prior to initiation of any study-specific procedures and treatment as confirmation of patient’s awareness and willingness to comply with the study requirements.
• Female patient aged greater or equal to 18 years and smaller or equal to 65 years.
• Patient with confirmed diagnosis of metastatic breast cancer.
• Patient with breast cancer after failure of combination chemotherapy for metastatic disease or having relapse within 6 months of adjuvant chemotherapy.
• Patient having clinically non-significant ECG and chest X-ray (PA view) as per PI discretion.
• Patient with ECOG status of 0 to 2 (both inclusive).
• Patient has adequate hematological, renal, and hepatic function as defined by the following: a.
• Absolute neutrophil count (ANC) greater or equal to 1500 cells per mm3 (1.5x10 raised to the power of 9 per L) b.
• Platelet count greater or equal to 100000 cells per mm3 (100x10 raised to the power of 9 per L) c.
• Hemoglobin greater or equal to 9 g per dL d.
• Serum creatinine smaller or equal to 1.95 mg per dL e.
• Creatinine clearance greater or equal to 60 mL per minute f.
• Total bilirubin smaller or equal to 1.8 mg per dL if patient had liver per bone metastasis, total bilirubin smaller or equal to 3.6 mg per dL will be considered.
• AST (SGOT) smaller or equal to 105 U per L if patient had liver or bone metastasis, AST smaller or equal to 210 U per L will be considered.
• ALT (SGPT) smaller or equal to 137.5 U per L if patient had liver per bone metastasis, ALT smaller or equal to 275 U per L will be considered.
• ALP (Alkaline phosphatase) smaller or equal to 375 U per L if patient had liver or bone metastasis, ALP smaller or equal to 750 U per L will be considered.
• Patient has expected survival of more than 3 months.
• Patient with negative serum pregnancy test at screening and negative urine pregnancy test at Day -1.
• Female patient of childbearing potential should be willing to use a reliable method of birth control during course of the study and at least 6 months following last dose of IP.
• Acceptable form of birth control include Tubal sterilization (tubal ligation performed more than one month before Study Day 1, transcervical tubal occlusion procedure performed more than six months before Study Day 1) Intrauterine Device (IUD) Two barrier methods used together (cervical cap, diaphragm contraceptive sponge, or vaginal spermicide plus a male or female condom).

Exclusion Criteria

• Patient with a history of other malignancies, except for adequately treated nonmelanoma skin cancer, curatively treated in-situ carcinoma of the cervix, in-situ carcinoma of the breast or other solid tumors with no evidence of recurrence for greater or equal to 5 years.
• Patient who experiences a severe hypersensitivity reaction to Paclitaxel other taxane product or the components of Paclitaxel protein-bound particles for injectable suspension (albumin-bound) or to any of the excipients.
• Patient who has previously received a taxane within the 30 days prior to randomization.
• Patient who is using gemcitabine.
• Patient who has not completely recovered from any toxicities from previous chemotherapy, hormone therapy, immunotherapy, or radiotherapies Grade 2 or higher by CTCAE, with the exception of alopecia.
• Patient with Sensory or Peripheral neuropathy of Grade 2 or higher by CTCAE.
• Patient with known brain metastases 8.
• Patient with severe myelosuppression.
• Patient with history or presence of sepsis or pneumonitis.
• Patient with history of difficulty with vascular access.
• Patient with positive test for alcohol breath test and or or urine drugs of abuse (except for morphine and or or benzodiazepines which are permissible when supported by a prescription).
• Patient with positive test for HIV 1 & 2 or HBsAg or HCV at screening.
• Patient with history of difficulty with donating blood or patient donated blood or participated in any clinical study with loss of greater or equal to 350 mL (1 unit) of blood prior to 3 months of screening or difficulty in accessibility of veins.
• Patient had major surgery within 30 days prior to randomization, or patient has not recovered from prior major surgery.
• Patient with known history or presence of any clinically significant disease or condition other than cancer unless determined as not clinically significant by the Investigator.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
To establish bioequivalence between the Test and the Reference product based on ln-transformed pharmacokinetic parameters Cmax, AUC0-t, and AUC0-infinity for unbound and total paclitaxel.	Day 35

Secondary Outcome Measures

Name	Time	Method
Tmax, Kel, T half, and AUC percent extrapolation will be reported for unbound and total paclitaxel.	Day 35
To assess safety and tolerability by considering reported adverse events, laboratory and clinical investigations, and vital signs	Every Visit

Trial Locations

Locations (11)

Anand Surgical Hospital Pvt Ltd; 🇮🇳 Ahmadabad, GUJARAT, India

Cancer Care Hospital; 🇮🇳 Kantha, GUJARAT, India

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

Global Hospital; 🇮🇳 Surat, GUJARAT, India

Health Point Hospital; 🇮🇳 Kolkata, WEST BENGAL, India

Marathwada Cancer Hospital and Research Institute; 🇮🇳 Aurangabad, MAHARASHTRA, India

MNJ Institute of Oncology and Regional Cancer Center; 🇮🇳 Hyderabad, TELANGANA, India

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

Savera Cancer and Multispeciality Hospital; 🇮🇳 Patna, BIHAR, India

Shankus Hospitals Pvt Ltd; 🇮🇳 Mahesana, GUJARAT, India

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Anand Surgical Hospital Pvt Ltd

🇮🇳Ahmadabad, GUJARAT, India

Dr Kalpeshkumar Keshavlal Prajapati

Principal investigator

9909914228

drkalpeshprajapati.research@gmail.com