Doxil/Caelyx BE Study

NCT05567601 | Completed Phase 1 FDA Drug

• 1 other identifier: BXU572940
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 14

Brief Summary

The aim of this study is to demonstrate the bioequivalence of DOXIL/CAELYX, 40 mg/m2 (IV infusion over 90 minutes) between two manufacturing facilities. According to the Food and Drug Administration (FDA), two products are considered to be bioequivalent when they are equal in the rate and extent to which the active pharmaceutical ingredient (API) becomes available at the site(s) of drug action. Any abnormalities of the safety endpoints (Clinical Laboratory Test, Electrocardiogram, Left Ventricular Ejection Fraction, Physical Examination) will be captured as Adverse Events.

Conditions

Ovarian Cancer; AIDS-related Kaposi Sarcoma; Multiple Myeloma; Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (3)

• Cmax based on encapsulated doxorubicin in patients

  Cmax=maximum observed plasma concentration.

  Day 1 (Cycle 1) and Day 28 (Cycle 2) at 15 minutes (min) prior to dosing as a baseline measurement and at 15 min, 30 min, 1 hour (h), 1 h 30 min, 1 h 35 min, 1h 45 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h, 48 h, 96 h, 168 h, 240 h, 336 h, 504 h post-dosing

• AUC0-t based on encapsulated doxorubicin in patients

  AUC0-t=area under the plasma concentration-time curve from time 0 to time t (interchangeable with AUC0-last).

  Day 1 (Cycle 1) and Day 28 (Cycle 2) at 15 minutes (min) prior to dosing as a baseline measurement and at 15 min, 30 min, 1 hour (h), 1 h 30 min, 1 h 35 min, 1h 45 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h, 48 h, 96 h, 168 h, 240 h, 336 h, 504 h post-dosing

• AUC0-∞ based on encapsulated doxorubicin in patients

  AUC0-∞=area under the plasma concentration-time curve from time 0 to infinite time, calculated as the sum of AUClast and Clast/λz, in which Clast is the last observed quantifiable concentration. The reference and the test products will be considered bioequivalent if the three 90% CIs for encapsulated doxorubicin fall within (0.80, 1.25).

  Day 1 (Cycle 1) and Day 28 (Cycle 2) at 15 minutes (min) prior to dosing as a baseline measurement and at 15 min, 30 min, 1 hour (h), 1 h 30 min, 1 h 35 min, 1h 45 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h, 48 h, 96 h, 168 h, 240 h, 336 h, 504 h post-dosing

Secondary Outcomes (4)

• Cmax based on total doxorubicin in patients

  Day 1 (Cycle 1) and Day 28 (Cycle 2) at 15 minutes (min) prior to dosing as a baseline measurement and at 15 min, 30 min, 1 hour (h), 1 h 30 min, 1 h 35 min, 1h 45 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h, 48 h, 96 h, 168 h, 240 h, 336 h, 504 h post-dosing

• AUC0-t based on total doxorubicin in patients

  Day 1 (Cycle 1) and Day 28 (Cycle 2) at 15 minutes (min) prior to dosing as a baseline measurement and at 15 min, 30 min, 1 hour (h), 1 h 30 min, 1 h 35 min, 1h 45 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h, 48 h, 96 h, 168 h, 240 h, 336 h, 504 h post-dosing

• AUC0-∞ based on total doxorubicin in patients

  Day 1 (Cycle 1) and Day 28 (Cycle 2) at 15 minutes (min) prior to dosing as a baseline measurement and at 15 min, 30 min, 1 hour (h), 1 h 30 min, 1 h 35 min, 1h 45 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h, 48 h, 96 h, 168 h, 240 h, 336 h, 504 h post-dosing

• Tumor response assessment

  Screening (28 days before Day 1) and between Day 46-56 (10 days before Cycle 3)

Study Arms (2)

Current Manufacturing Site

ACTIVE COMPARATOR

On Day 1 of Cycle 1 of the open-label treatment phase, patients will be randomized to receive drug from either current or new manufacturing site, and then after 28 days cross-over to the drug produced from the other manufacturing site in Cycle 2.

Drug: DOXIL/CAELYX

New Manufacturing Site

EXPERIMENTAL

On Day 1 of Cycle 1 of the open-label treatment phase, patients will be randomized to receive drug from either current or new manufacturing site, and then after 28 days cross-over to the drug produced from the other manufacturing site in Cycle 2.

Drug: DOXIL/CAELYX

Interventions

DOXIL/CAELYX DRUG

40 mg/m2 as a 90-minute IV infusion via a central venous catheter or peripheral vein

Also known as: doxorubicin hydrochloride liposome injection 2 mg/mL

Current Manufacturing Site; New Manufacturing Site

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be a man or woman aged from 18 to 75 years, inclusive.
• Patients with advanced or refractory ovarian or breast cancer, expected to require at least 2 cycles of DOXIL/CAELYX therapy at Screening, are eligible for treatment per this study protocol. This includes:
• Histologically or cytologically confirmed advanced ovarian cancer failing platinum-based chemotherapy
• Histologically or cytologically confirmed metastatic breast cancer after failing approved life-prolonging therapies
• Life expectancy greater than 6 months based on the clinical evaluation by the investigator at the time of Screening.
• Eastern Cooperative Oncology Group (ECOG) Performance status 0 to 2, inclusive.
• Recovered from the acute toxicity of any prior treatment (exemptions: alopecia, neuropathy Grade I). All toxicities from prior treatment should return to baseline or Grade I.
• Prior doxorubicin (or other anthracyclines) at cumulative dose of ≤ 240 mg/m2 or cumulative epirubicin dose ≤ 720 mg/m2 (calculated using doxorubicin equivalent doses: 1 mg doxorubicin = 1 mg DOXIL/CAELYX = 0.3 mg mitoxantrone = 0.25 mg idarubicin). Patients without any prior anthracycline exposure can also be included.
• Adequate liver function as determined by serum total bilirubin levels ≤ 1.2 mg/dL, and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels ≤ 2.5 x ULN.
• Adequate bone marrow function, as determined by an absolute neutrophil count (ANC) ≥ 1500/mm3 (or ≥ 1.5 x 109/L), a platelet count ≥ 100,000/mm3 (or ≥ 100 x 109/L), and a hemoglobin level ≥ 9 g/dL (or ≥ 90 g/L), in the absence of transfusion requirements or cytokine support for at least 7 days prior to enrolling in the study.
• Adequate renal function (mL/min), as determined by multiplying estimated glomerular filtration rate (e-GFR) by the body surface area (BSA) and dividing the value by 1.73 m2.
• Left ventricular ejection fraction (LVEF) within normal limits of the institution, as determined by multiple uptake gated acquisition (MUGA) or echocardiography.
• Female patients (of childbearing potential) must use medically acceptable methods of birth control (e.g., prescription oral contraceptives, contraceptive injections, contraceptive patches, intrauterine devices, the double-barrier method, male partner sterilization) before enrollment, throughout the study and for at least 8 months after the last DOXIL/CAELYX infusion.
• Male patients must agree to use an adequate contraception method as deemed appropriate by the Investigator and always use condoms when sexually active during the study. Medically acceptable methods of contraception that may be used by the patient and/or his partner include oral contraceptives, contraceptive injections, contraceptive patches, intrauterine devices, the double-barrier method, and surgical sterilization (vasectomy or tubal ligation) for minimally 6 months after the last administration of DOXIL/CAELYX. Sperm donation is not allowed during the study and for minimally 6 months after the last administration of DOXIL/CAELYX.
• Negative pregnancy test (urinary or serum beta-human chorionic gonadotropin \[β-HCG\]) at Screening (applicable to women of childbearing potential) within 7 days prior to starting treatment.

You may not qualify if:

• Positive history of known brain metastases or leptomeningeal disease. Patients with brain metastases can only be enrolled if the following conditions are all met:
• Brain metastases have been treated and stable for \> 4 weeks (\> 2 weeks after SRS/Cyberknife)
• No evidence for progression or hemorrhage after treatment
• Steroid treatment was discontinued at least 2 weeks prior to first administration of DOXIL/CAELYX
• Enzyme inducing anti-epileptic drugs were discontinued at least 4 weeks before the first administration of DOXIL/CAELYX
• Has a history of hypersensitivity reaction to doxorubicin HCl or other components of DOXIL/CAELYX.
• Has a history of prior or concomitant malignancy that requires other active treatment.
• Require any antineoplastic treatment while on the study (including therapy with another agent, radiation therapy, and/or surgical resection).
• Any major surgery, radiotherapy, or immunotherapy within the last 21 days (limited palliative radiation is allowed ≥ 2 weeks prior to the first dose; ≥ 4 weeks for whole brain radiotherapy). Chemotherapy regimens with delayed toxicity within the last 3 weeks (or within the last 6 weeks for prior nitrosourea or mitomycin C). Chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity within the last 2 weeks or 5 half-lives (whichever is shorter).
• Use of an investigational drug within 21 days or 5 half-lives (whichever is shorter) prior to the first dose of DOXIL/CAELYX.
• Impaired cardiac function including any of the following conditions within the past 6 months:
• Unstable angina
• QTc prolongation (QTc \> 470 millisecond) or other significant ECG abnormalities
• Coronary artery bypass graft surgery
• Symptomatic peripheral vascular disease

Sponsors & Collaborators

• Baxter Healthcare Corporation: lead

Study Sites (14)

HCG City Cancer Centre

Vijayawada, Andhra Pradesh, 520002, India

Location

Omega Hospital

Visakhapatnam, Andhra Pradesh, 530040, India

Location

Sanjeevani CBCC USA Cancer Hospital

Raipur, Chhattisgarh, 492001, India

Location

Unique Hospital Multispeciality & Research Institute

Surat, Gujarat, 395017, India

Location

Kailash Cancer Hospital and Research Centre

Goraj, Gurajat, 391760, India

Location

Medstar Speciality

Bangalore, Karnataka, 560092, India

Location

Oncoville Cancer Hospital & Research Centre

Bengaluru, Karnataka, 560072, India

Location

Sparsh Hospital & Critical Care Ltd.

Bhubaneshwar, Khndha-Orissa, 751007, India

Location

Indrayani Hospital

Pune, Maharashtra, 412105, India

Location

Erode Cancer Centre

Erode, Tamil Nadu, 638012, India

Location

Swami Har Shankaranand

Varanasi, Uttar Pradesh, 221005, India

Location

Sujan Surgical Cancer Hospital and Amravati Cancer Foundation

Amravati, 444605, India

Location

Kolhapur Cancer Center

Kolhāpur, 416234, India

Location

HCG Manavata Cancer Centre

Nashik, 422002, India

Location

MeSH Terms

Conditions

Ovarian Neoplasms; AIDS-related Kaposi sarcoma; Multiple Myeloma; Breast Neoplasms

Interventions

liposomal doxorubicin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2022
• First Posted: October 5, 2022
• Study Start: December 16, 2023
• Primary Completion: June 21, 2024
• Study Completion: June 21, 2024
• Last Updated: June 5, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Upon approval of a legitimate research request.
• Access Criteria: Research requests will be reviewed by qualified medical and scientific experts within the company. If Baxter agrees to the release of clinical data for research purposes, the requestor will be required to sign a data sharing agreement (DSA) in order to ensure protection of patient confidentiality and any intellectual property rights of Baxter prior to the release of any data.

Locations

IN (14)