multicenter, open label, three periods, three sequence single dose bioequivalence study of Doxorubicin Injection in female patients with ovarian cancer
- Conditions
- Health Condition 1: C569- Malignant neoplasm of unspecifiedovary
- Registration Number
- CTRI/2021/03/032185
- Lead Sponsor
- ForDoz Pharma Corp
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
1.Non-smoker, female patient 18 to 70 years of age (both inclusive).
2.Patients with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy and who are already receiving or scheduled to start Doxorubicin Hydrochloride liposomal injection 50 mg per m2 dose as monotherapy as confirmed by treatment and medical history.
3.Patients should have recovered from any toxic effects of previous chemotherapy as judged by the investigator.
4.Patients with life expectancy of at least 3 months.
5.ECOG performance status of less than or equal to 2.
6.Adequate hemopoeitic, renal and liver function.
Body system Parameters
Bone marrow function ANC more than or equal 1500/mm
Platelet count more than or equal to 100,000/mm
Haemoglobin more than or equal to 9.0 g/dL Renal function
Serum Creatinine less than or equal to 1.5 times ULN Hepatic function AST and ALT less than 3 times ULN (less than or equal to 5Ã?â?? ULN for liver metastasis) Alkaline phosphatase less than equal 3 times ULN less than or equal to 5 Ã?â?? ULN for bone metastasis) Bilirubin less than to 1.2 mg/dL
7.Sexually active women, unless surgically sterile (with documented evidence of hysterectomy / bilateral salpingectomy / bilateral oophorectomy at least 6 months prior to study drug administration) or postmenopausal for at least 12 consecutive months of spontaneous amenorrhea, must agree to use an effective method of avoiding pregnancy [including oral, transdermal, or implanted contraceptives (any hormonal method in conjunction with a secondary method), intrauterine device, female condom with spermicide, diaphragm with spermicide, absolute sexual abstinence, use of condom with spermicide by sexual partner or sterile (at least 6 months prior to study drug administration) sexual partner] for at least 4 weeks prior to study drug administration, during study and up to 6 months after the last dose of study drug. Cessation of birth control after this point should be discussed with a responsible physician. It is investigatorââ?¬Ë?s responsibility to ensure that above points regarding an effective methods of avoiding pregnancy are discussed with patient in detail and patient agreed for this and it is documented in source document. The investigator should ensure that the patient is using an effective method of avoiding pregnancy as per protocol.
8.Patient should able to understand and sign the written informed consent form and willing to follow the study requirements as per protocol.
9.Cancer patients receiving stable concomitant medications are allowed to participate, provided:
a. The concomitant medication and their dosing regimen is expected to remain same for all the study periods and clearly documented.
b. The concomitant medications do not interfere with the study drug.
Patients will be excluded from the study, if they meet any of the following
criteria:
1.History of allergy or hypersensitivity reactions to a conventional product of
Doxorubicin Hydrochloride or the components of Doxorubicin Hydrochloride Liposome Injection or any related compound at any dose or other anthracycline drugs, or granisetron or dexamethasone.
2.Patients who require a dose reduction to below 50 mg/m2.
3.Prior history of significant infusion-related reaction.
4.Concurrent use of calcium channel blockers or other cardiotoxic Medications such as cyclophosphamide.
5.Have received radiotherapy to mediastinal area or who are prone to radiation recall reaction due to recent radiotherapy.
6.For female of child bearing potential, positive pregnancy test at screening serum) and prior to dosing urine in period I.
7.Prior Doxorubicin exposure that would result in a total lifetime exposure of
550 mg per m2 or more after four cycles of treatment as confirmed by patient s
treatment history. (Prior use of other anthracyclines or anthracenodiones
should be included in calculations of total cumulative dosage
8.Patient having active opportunistic infection with mycobacteria,
cytomegalovirus, toxoplasma, P. carinii or other clinically significant
infection at screening or within 7 days prior to receiving the study drug.
9.Abnormal baseline findings considered by the investigator to indicate
conditions that might affect study endpoints.
10.Patients with history of other clinically significant concomitant disease
including gastrointestinal, pulmonary, endocrine, immunologic,
dermatologic, neurologic, psychological, musculoskeletal, cardiac, liver or
renal disease.
11.Alcohol or drug abuse or drug dependence within the preceding year.
12.The receipt of an investigational product (other than doxorubicin
hydrochloride liposome injection) or participation in a drug research
study within a period of 30 days or 5 half-lives (whichever is greater)
prior to receiving the first dose of investigational medicinal product in
the study.
13.Pregnant or breastfeeding female.
14.Patients with any of the below mentioned cardiac risks. Patients will
undergo evaluation by a cardiologist prior to study enrollment as applicable:
� Resting LVEF of less than or equal 50%
Note: Based on clinical suspicion of subclinical LV systolic dysfunction
by a Cardiologist/Investigator if required, patients may be referred to other
cardiac imaging methods such as strain, strain rate, cardiac MRI or nuclear
medicine etc. for further assessment of the cardiac risk.
� History of angina or coronary artery disease
� History of myocardial infarction
� NYHA (New York State Heart Association) class II-IV heart failure
� Clinically significant ventricular arrhythmia or tachyarrhythmia
� Clinically significant pericardial disease
� Electrocardiographic evidence of acute ischemic or significant
conduction system abnormalities
� Significant QTc prolongation or other significant ECG abnormalities.
� Any other cardiac illness that could lead to a safety risk to the patient in
case of enroll
Study & Design
- Study Type
- BA/BE
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To characterize the pharmacokinetic profile and to assess the Bioequivalence of the test product [Doxorubicin Hydrochloride Liposome Injection for intravenous infusion 2 mg/mL of ForDoz Pharma Corp., USA] to that of reference product [Doxorubicin Hydrochloride Liposome <br/ ><br>Injection for intravenous infusion 2 mg/mL by Sun Pharmaceutical Industries Ltd., India] in female patients with ovarian cancer <br/ ><br> <br/ ><br>Timepoint: A total of 22 blood samples each of 3.5 mL will be collected during each <br/ ><br>period. The pre-infusion blood sample (0.00) will be collected within one hour <br/ ><br>prior to the dosing. <br/ ><br>After start of intravenous infusion, blood samples (1 x 3.5 ml each) will be <br/ ><br>collected at 0.25, 0.50, 0.75, 1.00 (at the end of infusion), 1.25, 1.50, 2.00, 2.50, <br/ ><br>3.00, 3.50, 4.00, 5.00, 6.00, 9.00, 12.00, 24.00, 48.00, 96.00, 168.00, 240.00 <br/ ><br>and 336.00 hours
- Secondary Outcome Measures
Name Time Method To monitor the adverse events and to ensure the safety of patients.Timepoint: Physical examination,vital signs,ECG,laboratory <br/ ><br>evaluations and adverse event monitoring at period I(On Day 0), period II(On Day 28,29,30,31) & period III (day 56,57,58,59)