Bioequivalence study of Doxorubicin Hydrochloride (Pegylated liposomal)concentrate for solution for infusion 20 mg/10mL (2 mg/ml)in advancedovarian cancer and/or metastatic breast cancer patients under fed condition.

Suspended

• Conditions: Malignant neoplasm of breast of unspecified site, (2) ICD-10 Condition: C569||Malignant neoplasm of unspecifiedovary,

• Registration Number: CTRI/2015/04/005667
• Lead Sponsor: Dr Reddys Laboratories Limited

Brief Summary

This is a multicenter, open label, balanced, randomized, two-treatment,two-period, two-sequence, single dose, cross-over bioequivalence study to assess the bioequivalence between Test product Doxorubicin Hydrochloride (Pegylated liposomal) concentrate for solution for infusion 20 mg/10mL (2 mg/ml) of Dr. Reddy’s Laboratories Ltd, India, with that of Reference product Caelyx® 2mg/mL [Doxorubicin Hydrochloride (Pegylated Liposomal) concentrate for solution for infusion (20 mg/10mL)] of Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium in advanced ovarian cancer and/or metastatic breast cancer patients under fed condition. Subjects will receive 50mg/m2 dose(Period 1) of Doxorubicin Hydrochloride (Pegylated liposomal) concentrate for solution for infusion (either test or reference product) on the first day of the chemotherapy cycle under fed condition. For (period 2) subjects will recieve the same amount of dose(50mg/m2) on the first day of the next chemotherapy cycle under fed condition.The dose of Doxorubicin Hydrochloride for individual patient will be calculated according to body surface area (Calculated by Dubois formula). A total of 24 blood samples will be collected during each period. The pre infusion blood sample of 6 mL (00.00) will be collected within one hour prior to the dosing. During Intravenous infusion:Blood samples (1 x 6 mL each) will be collected at 0.083, 0.167, 0.333, 0.5 and 0.75 hours (hrs) after start of intravenous Infusion. After completion of Intravenous infusion: The post-dose blood samples (1 x 6 mL each) will be collected at end of infusion (i.e. 1 hour (hr)) and at 1.250, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96,120, 168, 216, 264 hr, and 336 hrs after start time of intravenous Infusion.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-06-18
• Last Update Posted: 2018-12-14

Recruitment & Eligibility

• Status: Suspended
• Sex: Female
• Target Recruitment: 58

Inclusion Criteria

• Ability to understand and provide written informed consent prior to participation in the study 2.
• Patients with advanced ovarian cancer requiring Doxorubicin and who have failed a first-line platinum-based chemotherapy regimen.
• Cardiac function (left ventricular ejection fraction [LVEF] ≥50%.
• Patient should have recovered from any toxic effects of previous chemotherapy as judged by the Investigator.
• Patients with life expectancy of at least 3 months.
• Able to comply with study requirement in opinion of Principal Investigator.
• 7.Adequate recovery from recent surgery.
• At least 1 week must have elapsed from the time of minor surgery; at least 4 weeks must have elapsed from the time of major surgery.
• 8.Sexually active women, unless surgically sterile (at least 6 months prior to Study drug administration) or postmenopausal for at least 12 consecutive months, must use an effective method of avoiding pregnancy.
• Adequate Bone marrow function ANC ≥ 1500/mm3 Platelet count ≥ 100,000/mm3 Haemoglobin ≥ 9.0 g/dl 10.
• Adequate Renal Function Serum Creatinine < 1.5 x upper limit of normal(ULN) 11.
• Adequate Hepatic Function AST and ALT < 2.5 x ULN Alkaline phosphatase < 2 x ULN Bilirubin < ULN.

Exclusion Criteria

• Patients who are Pregnant, Breast Feeding, of childbearing potential without a negative pregnancy test prior to baseline, Female of childbearing potential unwilling to use barrier contraceptive precautions throughout the trial.
• 2.Patients with an ECOG (Eastern Cooperative Oncology group) Performance Status Score > 3 3.
• If total cumulative dose of Doxorubicin HCl approaches 450 mg/m2 4.
• Active opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma, P.carinii or other microorganism if under treatment with myelotoxic drugs.
• Clinically significant liver or kidney disorders.
• History of hypersensitivity reactions attributed to a conventional formulation of Doxorubicin Hydrochloride or the components of Caelyx 7.Use of any recreational drugs or history of drug addiction 8.
• Known brain metastasis.
• Pre-existing motor or sensory neurotoxicity of a severity ≥ grade 2 by NCI criteria.
• Other serious illness or medical condition that would prohibit the understanding and giving of informed consent.
• A positive hepatitis screen including hepatitis B surface antigen, HCV and HAV antibodies.
• A positive test result for HIV antibody and/or syphilis.
• The receipt of an investigational product, or participation in a drug research study within a period of 30 days prior to the first dose of investigational Product (Elimination half-life of the study drug should be taken into consideration for inclusion of the patient in the 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.
• Abnormal baseline findings considered by the investigator to indicate conditions that might affect study endpoints.
• Current or relevant previous history of serious, severe or unstable (acute or progressive) physical or psychiatric illness, any medical disorder that may require treatment or make the patient unlikely to fully complete the study, or any condition that presents undue risk from the study medication or procedures.
• History of donation of blood/loss of blood (without replenishment) (1unit or 350 ml) within 90 days prior to receiving the first dose of investigational medicinal product in the study.
• Uncontrolled hypertension (systolic blood pressure [BP] >180 or diastolic BP >100mm Hg) or uncontrolled cardiac arrhythmias (Patients with hypertension controlled by antihypertensive therapies are eligible).
• History of cerebrovascular accident (CVA), MI within 6 months or venous thrombosis within 12 weeks.
• (Patients with previous history of venous thrombosis on a stable dose of anticoagulation are allowed).
• Past or current history of neoplasm other than the entry diagnosis with the exception of treated non-melanoma skin cancer or carcinoma in situ of the cervix, or other cancers cured by local therapy alone and a disease free survival ≥ 5 years.
• Patients who have taken any potent CYP3A4 inhibitors/inducers ≤ 14days prior to enrollment including but not limited to: ketoconazole,itraconazole, troleandomycin, clarithromycin, erythromycin,ritonavir,indinavir, nelfinavir, saquinavir, amprenavir, nefazodone, fluvoxamine,diltiazem, verapamil, mibefradil, cimetidine, cyclosporine, and grapefruit juice.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
To Assess the bioequivalence between Doxorubicin Hydrochloride (Pegylated liposomal) concentrate for solution for infusion 20 mg/10mL (2 mg/ml) of Dr.Reddy’s Laboratories Ltd, India, with that of Caelyx® 2mg/mL [Doxorubicin Hydrochloride (Pegylated Liposomal) concentrate for solution for infusion (20 mg/10mL)] of Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium in advanced ovarian cancer and/or metastatic breast cancer patients under fed condition.	Blood samples (1 x 6 mL each) will be collected at 0.083, 0.167, 0.333,0.5 and 0.75 hours (hrs) after start of intravenous Infusion. After completion of intravenous infusion the post-dose blood samples (1 x 6 mL each) will be collected at end of infusion (i.e. 1 hour (hr)) and at 1.250, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96,120,168, 216, 264 hr, and 336 hrs after start time of intravenous Infusion.

Secondary Outcome Measures

Name	Time	Method
To monitor the adverse events and to ensure the safety of the patients	NA

Trial Locations

Locations (15)

Apple Hospital; 🇮🇳 Surat, GUJARAT, India

Asirvatham Speciality Hospital; 🇮🇳 Madurai, TAMIL NADU, India

B. P. Poddar Hospital & Medical Research; 🇮🇳 Kolkata, WEST BENGAL, India

Baraskar Hospital and Research Centre; 🇮🇳 Nagpur, MAHARASHTRA, India

Chittaranjan National Cancer Institute; 🇮🇳 Kolkata, WEST BENGAL, India

City Cancer Centre; 🇮🇳 Krishna, ANDHRA PRADESH, India

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

Dr. GVN Cancer Institute; 🇮🇳 Tiruchirappalli, TAMIL NADU, India

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

Kailash Cancer Hospital & Research Centre; 🇮🇳 Vadodara, GUJARAT, India

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Apple Hospital

🇮🇳Surat, GUJARAT, India

Dr Patel Ghanshyam Nanubhai

Principal investigator

02616696078

gnonco@gmail.com