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

November 19, 2019 updated by: Ayana Pharma Ltd.,

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.

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 .

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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%.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
52

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
    • Andhra Pradesh
      • Hyderabad, Andhra Pradesh, India, 500004
        • MNJ Institute of Oncology & Regional Cancer Center
      • Vijayawada, Andhra Pradesh, India, 520002
        • HCG City Cancer Centre
      • Visakhapatnam, Andhra Pradesh, India, 530017
        • Mahatma Gandhi Cancer Hospital & Research Institute
    • Gujarat
      • Surat, Gujarat, India, 395002
        • Nirmal Hospital Pvt. Ltd.
      • Sūrat, Gujarat, India, 395002
        • Unique Hospital - Multispeciality and Research Institute
      • Vadodara, Gujarat, India, 391760
        • Kailash Cancer Hospital and Research Center
      • Vadodara, Gujarat, India, 390021
        • Aman Hospital and Research Center
    • Karnataka
      • Mysore, Karnataka, India, 570001
        • K R Hospital
    • Maharashtra
      • Nashik, Maharashtra, India, 422002
        • HCG Manavata Cancer Centre
      • Nashik, Maharashtra, India, 422 002
        • Apex Wellness Rishikesh Hospital
      • Pune, Maharashtra, India, 411013
        • Noble Hospital Pvt Ltd.
    • Odisha
      • Bhubaneshwar, Odisha, India, 751007
        • Sparsh Hospitals & Critical Care (P) Ltd.
    • Tamil Nadu
      • Chennai, Tamil Nadu, India, 602105
        • Saveetha Medical College & Hospital
      • Chennai, Tamil Nadu, India, 600116
        • Sri Ramachandra Medical Centre
      • Coimbatore, Tamil Nadu, India, 641005
        • VGM Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • 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 Names:
  • Doxorubicin Hydrochloride Liposomal injection 20 mg/10 mL

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Throughout 15 days after both dosing.
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.
Throughout 15 days after both dosing.
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.
Throughout 15 days after both dosing.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Throughout 15 days after both dosing.
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.
Throughout 15 days after both dosing.
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.
Throughout 15 days after both dosing.
Assessment of safety
Time Frame: Troughout 42 days after first dosing
Assessment of incidence of adverse events
Troughout 42 days after first dosing

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ayana Pharma Ltd.,

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Lambda Therapeutic Research Ltd.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Rakesh J Patel, MD Pharm, Lambda Therapeutic Research Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 29, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 8, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 7, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 17, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 20, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 24, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 20, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 19, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • LC-101-02
  • 0384-18 (Other Identifier: Lambda)
  • CTRI/2018/07/014835 (Registry Identifier: CTRI)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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