Bioequivalence Study of Doxorubicin Hydrochloride Liposome Injection (Lipodox®) in Chinese Patients

NCT05273944 | Unknown Phase 1

• 1 other identifier: DHLI-BC/OC-BE-001
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Bioequivalence study is proposed to be carried out on patients of breast cancer/ ovarian cancer, who are administrated for Doxorubicin Hydrochloride Liposomal Injection Lipodox® or Caelyx® in a dose of 50 mg/m2.

Conditions

Breast Cancer; Ovarian Cancer

Outcome Measures

Primary Outcomes (3)

• Cmax

  Maximum observed plasma concentration

  Pre-dose (within 60 minutes), 15,30, 45,60,75,90minutes after the beginning of infusion, 15minutes, 30minutes, 1,3,5,8,16,24,36,48,96,168,240,336hours after infusion completed

• AUC[0-t]

  Area under the plasma concentration-time curve from time 0 to last time of quantifiable concentration

  Pre-dose (within 60 minutes), 15,30, 45,60,75,90minutes after the beginning of infusion, 15minutes, 30minutes, 1,3,5,8,16,24,36,48,96,168,240,336hours after infusion completed

• AUC[0-∞]

  Area under the plasma concentration-time curve from 0 extrapolated to infinite time

  Pre-dose (within 60 minutes), 15,30, 45,60,75,90minutes after the beginning of infusion, 15minutes, 30minutes, 1,3,5,8,16,24,36,48,96,168,240,336hours after infusion completed

Secondary Outcomes (8)

• AUC[0-48hours]

  Pre-dose (within 60 minutes) , 15, 30, 45, 60, 75, 90minutes after the beginning of infusion, 15 minutes, 30 minutes, 1, 3, 5, 8, 16, 24, 36, 48hours after infusion completed

• AUC[48hours-t]

  48hours post-dose to the 336hours post-dose

• Tmax

  Pre-dose (within 60 minutes), 15,30, 45,60,75,90minutes after the beginning of infusion, 15minutes, 30minutes, 1,3,5,8,16,24,36,48,96,168,240,336hours after infusion completed

• λz

  Pre-dose (within 60 minutes), 15,30, 45,60,75,90minutes after the beginning of infusion, 15minutes, 30minutes, 1,3,5,8,16,24,36,48,96,168,240,336hours after infusion completed

• t1/2z

  Pre-dose (within 60 minutes), 15,30, 45,60,75,90minutes after the beginning of infusion, 15minutes, 30minutes, 1,3,5,8,16,24,36,48,96,168,240,336hours after infusion completed

Study Arms (2)

Reference product-R

ACTIVE COMPARATOR

Caelyx® (Janssen-Cilag International NV); 20 mg/10 mL (50 mg/m2 dose). As this is a crossover study, subjects receiving the Reference Product (Caelyx®) in Cycle 1, will receive the Test Product (Lipodox®) in Cycle 2. Cycle is defined as 28-42 days (RT).

Drug: Doxorubicin Hydrochloride Liposome Injection

Test Product-T

EXPERIMENTAL

Lipodox® (Sun Pharmaceutical Industries Ltd.); 20 mg/10 mL (50 mg/m2 dose). As this is a crossover study, subjects receiving the Test Product (Lipodox®) in Cycle 1, will receive the Reference Product (Caelyx®) in Cycle 2. Cycle is defined as 28-42 days (TR).

Drug: Doxorubicin Hydrochloride Liposome Injection

Interventions

Doxorubicin Hydrochloride Liposome Injection DRUG

50mg/m2, intravenous drip on Day 1 of each cycle. On Day 1 of Cycle 1 patients will receive either reference or test product. On Day 1 of Cycle 2, patients will crossover to the alternate reference or test formulation. To measure pharmacokinetic paratemers of Caelyx® versus Lipodox®.

Also known as: Caelyx®/Lipodox®

Reference product-R; Test Product-T

Eligibility Criteria

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

You may qualify if:

• The subjects fully understand the purpose, nature, methods and possible adverse reactions of the study, voluntarily participate in the study, and sign informed consent before the study procedure begins;
• Adult female subjects between 18 to 75 years of age (both inclusive) at the time of screening visit. Body weight is greater than or equal to 40.0 kg. Body surface area (BSA) is less than 1.8 m2;
• Subjects with histologically or cytological proven: 1) Advanced ovarian cancer patients who had previously failed first-line platinum-containing chemotherapy; Or 2) metastatic breast cancer;
• ECOG performance status ≤ 2;
• Life expectancy of at least 3 months;
• Adequate renal, hepatic function:
• Neutrophils ≥1.5×109/L;
• Leukocyte≥3×109/L;
• Platelet count ≥ 80×109/L;
• Hemoglobin (Hb) ≥ 90g/L;
• Serum creatinine ≤ 1.5 x ULN;
• AST ≤ 2.5 x ULN, ALT ≤ 2.5 x ULN (for liver metastasis≤ 5 x ULN);
• Prothrombin time (PT)/activated partial thromboplastin time (APTT) ≤ 1.5 x ULN;
• Total bilirubin≤ 1.5 x ULN (for liver metastasis≤ 3 x ULN);
• Alkaline phosphatase ≤ 2.5 x ULN;

You may not qualify if:

• History of allergy to doxorubicin or any components of doxorubicin; or those with allergic constitution: such as those who are allergic to two or more drugs and food;
• Previous treatment with Doxorubicin Liposome, and discontinue treatment due to treatment failure or severe adverse reactions;
• Patients who have previously received more than 400 mg/m2 doxorubicin (Conversion of other anthracyclines and anthraquinone: 1 mg doxorubicin is equivalent to 2 mg epirubicin, or 2 mg pirarubicin, or 2 mg daunorubicin, or 0.5 mg dimethoxy-daunorubicin , or 0.45 mg mitoxantrone), or severe cardiotoxicity from prior exposure to anthracyclines;
• Positive history of known spinal cord compression or brain metastases (unless asymptomatic, stable for more than 4 weeks, steroid treatment was discontinued at least 4 weeks prior to first administration of Lipodox®/ Caelyx®, and no radiographic evidence of significant edema around the tumor lesion). Untreated patients with disease progression due to brain metastases in the last treatment prior to screening;
• Subjects with other known active malignancies that require treatment within 5 years;
• Patients with abnormal cardiac function: ECG examination, QTc\>480ms; left ventricular ejection fraction(LVEF)\<55%；congestive heart failure, myocardial infraction, or uncontrolled angina pectoris of New York Heart Society≥2 within 6 months prior to enrollment; have undergone heart bypass surgery; Tropoin≥1.5 x ULN；N-terminal brain natriuretic peptide ≥1.5 x ULN; The investigator evaluated the overall cardiac function of the subjects by integrating all examination items.
• Patients with poor control of hypertension (systolic≥160 mmHg, diastolic\>80 mmHg;
• Diabetes blood glucose control is not up to standard, fasting blood glucose \>11.1 mol/L, or accompanied by diabetic complications (diabetic nephropathy, peripheral neuropathy);
• Radiation therapy or chemotherapy drugs (paclitaxel, cyclosporine, dexrazoxane, cytarabine, streptozotocin, etc.) within 4 weeks before study administration prior to administration, or other anti-tumor therapies such as endocrine therapy, traditional Chinese medicine, and local radiation therapy to relieve pain;
• Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug, or plan to undergo major surgery during the study period and those who have undergone surgery that may affect drug absorption, distribution, metabolism, and excretion;
• Use of drugs that induce or inhibit liver drug enzymes in the previous 4 weeks prior to administration and during the study (such as: Barbiturates, carbamazepine, phenytoin, griseofulvin);
• The special diet within 7 days before the study administration may affect drug absorption, distribution, metabolism and excretion during the study, including but no limited to: taking special diets that may image drug metabolism including dragon fruit, mango, grapefruit, lime, carambola, chocolate, or by the preparation of food or drink, or a diet containing caffeine, xanthine, etc;
• Patients who consumed excessive amounts of tea, coffee, and/or caffeine-rich beverages (more than 8 cups, one cup=250mL) daily for 3 months prior to administration;
• Patients who smoked more than 5 cigarettes per day during the 3 months prior to administration, or who did not agree to refrain from using any tobacco products during the study;
• Drinking more than 14 units of alcohol per week in the 3 months prior to administration (1 unit of alcohol≈360mL beer or 45mL 40% alcoholic spirits or 150mL wine);

Sponsors & Collaborators

• Shenzhen Kangzhe Pharmaceutical Co., Ltd.: lead
• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: collaborator
• Hunan Cancer Hospital: collaborator
• The Second Affiliated Hospital of Chongqing Medical University: collaborator
• First Affiliated Hospital of Jinan University: collaborator
• Zhejiang Provincial People's Hospital: collaborator
• Yuncheng Central Hospital: collaborator
• Shantou Central Hospital: collaborator
• Yuebei People's Hospital: collaborator
• Cancer Hospital of Guizhou Province: collaborator
• Guangzhou Panyu Central Hospital: collaborator
• Dongguan People's Hospital: collaborator

Study Sites (1)

Sun Yat-Sun Memorial Hospital, Sun Yat-Sun University

Guangzhou, Guangdong, 510120, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Ovarian Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland 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

Central Study Contacts

Herui Yao

CONTACT

81332107; yaoherui@163.com

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: February 10, 2022
• First Posted: March 10, 2022
• Study Start: July 28, 2021
• Primary Completion: March 31, 2022
• Study Completion: April 30, 2022
• Last Updated: March 10, 2022

Record last verified: 2022-02

Locations

CN (1)