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Trial record 2 of 2159 for:    doxorubicin

A Study of Doxorubicin Hydrochloride Liposome Injection in Subjects With Ovarian Cancer.

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ClinicalTrials.gov Identifier: NCT03681548
Recruitment Status : Completed
First Posted : September 24, 2018
Last Update Posted : July 3, 2019
Sponsor:
Collaborator:
Lambda Therapeutic Research Ltd.
Information provided by (Responsible Party):
Ayana Pharma Ltd.,

Brief Summary:
Bioequivalence study is proposed to be carried out on patients of ovarian cancer, who are already receiving or who in the opinion of their treating physicians are candidates for Doxorubicin liposomal injection therapy .

Condition or disease Intervention/treatment Phase
Ovarian Cancer Recurrent Drug: Doxorubicin Hydrochloride Liposome Injection Phase 1

Detailed Description:
This study is a randomized, open label, two arm, single dose, crossover bioequivalence study. This study will be conducted in female subjects aged 18 to 65 years diagnosed with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy and who are already receiving or scheduled to start therapy with Doxorubicin Hydrochloride Liposome Injection product. Each subject will be randomized to one of the two treatment sequences (RT or TR) according to a randomization scheme prepared prior to start of the trial. Serial blood samples for determination of free and liposomal encapsulated doxorubicin plasma concentration for PK analysis will be obtained in each cycle., This study has an adaptive 2-stage design. A sufficient number of subjects with ovarian cancer shall be recruited to have approximately 42 evaluable subjects completing all follow up procedures (Stage 1). An interim analysis of free and encapsulated doxorubicin will be performed at the end of Stage 1. If the bioequivalence of encapsulated and free doxorubicin has been established, then the study will be stopped. Otherwise, the study may continue into Stage 2 with additional number of ovarian cancer subjects. A final evaluation of bioequivalence based on free and encapsulated doxorubicin will be performed at the end of Stage 2 and will include all enrolled subjects completing the study. Bioequivalence criteria: the 94.12% confidence interval of the ratio of geometric means of TEST to REFERENCE for Cmax, AUC0-t, AUC0-∞, for free and encapsulated doxorubicin should be between 80.00% and 125.00%.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 52 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Bioequivalence study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Open Label, Two Arm, Single Dose, Crossover, Bioequivalence Study of Ayana Pharma's Doxorubicin Hydrochloride Liposome Injection (LC-101) (Investigational Product) and the US Reference Standard Doxorubicin Hydrochloride Liposome Injection (Sun Pharma), in Subjects With Ovarian Cancer.
Actual Study Start Date : August 29, 2018
Actual Primary Completion Date : February 8, 2019
Actual Study Completion Date : March 7, 2019


Arm Intervention/treatment
Active Comparator: Reference Product - R
Doxorubicin Hydrochloride Liposome Injection (Sun Pharma); 20 mg/10 mL i.e. 2 mg/mL (50mg/m2 dose). As this is a cross over study, subjects receiving in Cycle 1 the Reference Product (doxorubicin hydrochloride liposome injection SunPharma), will receive in Cycle 2 the Test Product (doxorubicin hydrochloride liposome injection (Ayana); after at least 4 weeks (RT).
Drug: Doxorubicin Hydrochloride Liposome Injection
50mg/m2, IV 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
Other Name: Doxorubicin Hydrochloride Liposomal injection 20 mg/10 mL

Experimental: Test Product - T
Doxorubicin Hydrochloride Liposome Injection (Ayana Pharma Ltd); 20 mg/10 mL i.e. 2 mg/mL (50mg/m2 dose). As this is a cross over study, subjects receiving in Cycle 1 the Test Product (doxorubicin hydrochloride liposome injection (Ayana)will receive in Cycle 2 the Reference Product (doxorubicin hydrochloride liposome injection SunPharma); after at least 4 weeks (RT).
Drug: Doxorubicin Hydrochloride Liposome Injection
50mg/m2, IV 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
Other Name: Doxorubicin Hydrochloride Liposomal injection 20 mg/10 mL




Primary Outcome Measures :
  1. Assessment of bioequivalence using Cmax of encapsulated and free doxorubicin in plasma [ Time Frame: Throughout 15 days after both dosing. ]
    Assessment of bioequivalence of LC-101 (TEST Product) in comparison to the US Reference standard (REFERENCE product). Bioequivalence will be assessed using maximum plasma doxorubicin concentration (Cmax) of encapsulated and free doxorubicin measurements in plasma.

  2. Assessment of bioequivalence using AUC (0-t) of encapsulated and free doxorubicin in plasma [ Time Frame: Throughout 15 days after both dosing. ]
    Assessment of bioequivalence of LC-101 (TEST Product) in comparison to the US Reference standard (REFERENCE product). Bioequivalence will be assessed using areas under the plasma concentration versus time curve calculated from 0 to the last measurable observation (AUC 0-t) of encapsulated and free doxorubicin measurements in plasma.

  3. Assessment of bioequivalence using AUC (0-inf) of encapsulated and free doxorubicin in plasma [ Time Frame: Throughout 15 days after both dosing. ]
    Assessment of bioequivalence of LC-101 (TEST Product) in comparison to the US Reference standard (REFERENCE product). Bioequivalence will be assessed using areas under the plasma concentration versus time curve calculated from 0 to infinity (AUC 0-inf) of encapsulated and free doxorubicin measurements in plasma.


Secondary Outcome Measures :
  1. Assessment of bioequivalence using Cmax of total doxorubicin in plasma [ Time Frame: Throughout 15 days after both dosing. ]
    Assessment of bioequivalence of LC-101 (TEST Product) in comparison to the US Reference standard (REFERENCE product). Bioequivalence will be assessed using Cmax of total doxorubicin measurements in plasma.

  2. Assessment of bioequivalence using AUC (0-t) of total doxorubicin in plasma [ Time Frame: Throughout 15 days after both dosing. ]
    Assessment of bioequivalence of LC-101 (TEST Product) in comparison to the US Reference standard (REFERENCE product). Bioequivalence will be assessed using AUC (0-t) of total doxorubicin measurements in plasma.

  3. Assessment of bioequivalence using AUC (0-inf) total doxorubicin as secondary analyte [ Time Frame: Throughout 15 days after both dosing. ]
    Assessment of bioequivalence of LC-101 (TEST Product) in comparison to the US Reference standard (REFERENCE product). Bioequivalence will be assessed using AUC (0-inf) of total doxorubicin measurements in plasma.

  4. Assessment of safety [ Time Frame: Troughout 42 days after first dosing ]
    Assessment of incidence of adverse events



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adult female subjects between 18 to 65 years of age (both inclusive) at the time of screening visit.
  2. Subjects with histologically or cytological proven ovarian cancer, whose disease has progressed or recurred after platinum-based chemotherapy and scheduled to start therapy with or who are already receiving an approved dose of 50 mg per meter square Doxorubicin Hydrochloride Liposome Injection product.
  3. Subjects expected to be able to receive both doses of Doxorubicin Hydrochloride Liposome Injection.
  4. Subjects eligible for receiving a dose of 50 mg per meter square of Doxorubicin Hydrochloride Liposome Injection.
  5. Subjects with Performance less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) performance scale
  6. Cardiac function (LVEF) greater than or equal to 50 percentage.
  7. Adequate renal, hepatic and bone marrow function without blood product or hematopoietic growth factor support.
  8. Subjects able to understand the investigational nature of this study.
  9. Availability of subject for the entire study period and willingness to adhere to protocol requirements.
  10. For subjects of child-bearing potential, serum beta HCG pregnancy test at screening and urine pregnancy test prior to dosing must be negative and subjects agree to use an acceptable and effective approved method of contraception
  11. Subjects of non-childbearing potential who are either surgically sterile (hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or greater than 1 year postmenopausal with follicle stimulating hormone in the postmenopausal range
  12. Signed written informed consent.

Exclusion Criteria:

  1. Subjects with history or presence of significant:

    • Allergy or significant history of hypersensitivity or idiosyncratic reactions to a conventional formulation of Doxorubicin Hydrochloride and/or any components of Doxorubicin Hydrochloride liposome injection.
    • Clinically significant pulmonary, hepatic, renal, bone marrow, gastrointestinal, endocrine, immunologic, dermatologic, musculoskeletal, neurological or psychiatric disease.
    • Impaired cardiac function
  2. Alcohol dependence, alcohol abuse or drug abuse or addiction with any recreational drug within the past one year.
  3. Active opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma, p. carinii or other microorganism (bacterial, viral or fungal).
  4. Clinically significant illness (except ovarian cancer) within four weeks prior to dosing.
  5. Prior radiation therapy to mediastinum
  6. Concomitant use of other cytotoxic or cytostatic drugs or of radiotherapy within four weeks prior to dosing
  7. Subject under treatment of myelotoxic drugs, other than doxorubicin (liposomal).
  8. Use of prescription or non-prescription herbal and dietary supplements, within 7 days prior to dosing.
  9. Subjects with other known active malignancies requiring treatment within 3 years (except for ovarian and/or skin cancer).
  10. Subjects with known brain metastasis and/or subjects considered for radiotherapy treatment.
  11. Positive result to any of the following: HIV-1/2, hepatitis A, B and C; syphilis.
  12. Use of CYP3A4 enzyme-modifying drugs in the previous 30 days prior to dosing and during the study
  13. Subjects who have:

    • Systolic blood pressure less than 90 mmHg or more than 160 mmHg
    • Diastolic blood pressure less than 60 mmHg or more than 95 mmHg
    • Pulse rate below 55 per min. or above 100 per min14.
  14. Subjects with abnormal laboratory parameters
  15. Subject is currently enrolled in, or has not yet completed a period of at least 30 days since ending other investigational device or drug trial(s).
  16. Subjects who are legally detained in an official institute.
  17. Subjects with prior doxorubicin exposure that would result in a total lifetime exposure of 550 mg per meter square or more after four cycles of treatment.
  18. Has any condition that, in the opinion of the investigator, would make participation not be in the best interest (e.g., compromise the well-being) of the subject or that could prevent, limit, or confound the protocol-specified assessments
  19. Females of childbearing potential unwilling to use acceptable contraception (as identified in the protocol) throughout the trial and for 6 months after the last dose of study drug.
  20. Pregnant or breast-feeding subjects.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03681548


Locations
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India
MNJ Institute of Oncology & Regional Cancer Center
Hyderabad, Andhra Pradesh, India, 500004
HCG City Cancer Centre
Vijayawada, Andhra Pradesh, India, 520002
Mahatma Gandhi Cancer Hospital & Research Institute
Visakhapatnam, Andhra Pradesh, India, 530017
Apple Hospital
Surat, Gujarat, India, 395002
Nirmal Hospital Pvt. Ltd.
Surat, Gujarat, India, 395002
Unique Hospital - Multispeciality and Research Institute
Sūrat, Gujarat, India, 395002
Aman Hospital and Research Center
Vadodara, Gujarat, India, 390021
Kailash Cancer Hospital And Research Center
Vadodara, Gujarat, India, 391760
Sri Venkateshwara Hospital
Bangalore, Karnataka, India, 560068
K R Hospital
Mysore, Karnataka, India, 570001
Apex Wellness Rishikesh Hospital
Nashik, Maharashtra, India, 422 002
HCG Manavata Cancer Centre
Nashik, Maharashtra, India, 422002
Noble Hospital Pvt Ltd.
Pune, Maharashtra, India, 411013
Sparsh Hospitals & Critical Care (P) Ltd.
Bhubaneshwar, Odisha, India, 751007
Sri Ramachandra Medical Centre
Chennai, Tamil Nadu, India, 600116
Saveetha Medical College & Hospital
Chennai, Tamil Nadu, India, 602105
VGM Hospital
Coimbatore, Tamil Nadu, India, 641005
Sponsors and Collaborators
Ayana Pharma Ltd.,
Lambda Therapeutic Research Ltd.
Investigators
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Study Director: Rakesh J Patel, MD Pharm Lambda Therapeutic Research Ltd.

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Responsible Party: Ayana Pharma Ltd.,
ClinicalTrials.gov Identifier: NCT03681548     History of Changes
Other Study ID Numbers: LC-101-02
0384-18 ( Other Identifier: Lambda )
CTRI/2018/07/014835 ( Registry Identifier: CTRI )
First Posted: September 24, 2018    Key Record Dates
Last Update Posted: July 3, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ayana Pharma Ltd.,:
liposomal doxorubicin injection
bioequivalence study
ovarian cancer
Additional relevant MeSH terms:
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Doxorubicin
Liposomal doxorubicin
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action