A Pivotal Bioequivalence Study of DOXIL/CAELYX (Doxorubicin HCL) in Patients With Advanced or Refractory Solid Malignancies Including Patients With Ovarian Cancer

December 3, 2015 updated by: Janssen Research & Development, LLC

A Pivotal Bioequivalence Study of DOXIL/CAELYX Manufactured at a New Site in Subjects With Advanced or Refractory Solid Malignancies Including Subjects With Ovarian Cancer.

The purpose of this study is to support the qualification of a replacement manufacturing site for DOXIL/CAELYX (doxorubicin HCL).

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 is a randomized (individuals will be assigned in a random order to study treatment sequences), open-label (identity of assigned treatment sequences will be known), single dose, 2-cycle, crossover (patients will receive both treatments in a random order) bioequivalence study of DOXIL/CAELYX (doxorubicin HCL) in patients with advanced or refractory solid malignancies (including patients with ovarian cancer). This study has an adaptive 2-stage design. Bioequivalence based on encapsulated doxorubicin will be tested at the end of Stage 1 using data from at least 24 ovarian cancer patients. An interim analysis of free doxorubicin will be performed at the end of Stage 1 using data from 42 patients of all cancer types. The study may continue into Stage 2 with additional patients of all cancer types; and final evaluation of bioequivalence for free doxorubicin will be performed at the end of Stage 2. The study will include a screening phase followed by an open-label treatment phase consisting of 2 doxorubicin treatment cycles and an end-of-treatment visit on Cycle 3, Day 1. Participants may enter an optional extension phase after 2 cycles. Safety will be monitored throughout the study. Blood samples for pharmacokinetic analysis will be obtained from all participants at specified times over 29 days after starting each study drug administration in Cycles 1 and 2 for determination of plasma concentrations of encapsulated and free doxorubicin.

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.
54

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

  • Belgium
      • Brussel, Belgium
      • Wilrijk, Belgium
  • Spain
      • Barcelona, Spain
      • Madrid, Spain
      • Valencia, Spain
  • United Kingdom
      • London, United Kingdom
  • United States
    • Tennessee
      • Nashville, Tennessee, United States
    • Texas
      • San Antonio, Texas, United States

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosed with advanced or refractory solid malignancies: histologically or cytologically confirmed advanced ovarian cancer failing platinum-based chemotherapy; histologically or cytologically confirmed metastatic breast cancer after failing approved life-prolonging therapies; any histologically or cytologically confirmed solid malignancy that is metastatic or unresectable, and for which standard treatment is no longer an option
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Recovered from acute toxicity of any prior treatment (exemptions: alopecia, grade-1 neuropathy)
  • Prior doxorubicin (or other anthracyclines) at cumulative dose of <=360 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)
  • Adequate liver, bone marrow, and renal function according to protocol-defined parameters
  • Left ventricular ejection fraction (LVEF) within normal limits of the institution as determined by multiple uptake gated acquisition (MUGA) or echocardiography
  • Agrees to protocol-defined use of effective contraception
  • Negative pregnancy test at screening (applicable to women of child bearing potential) within 7 days prior to starting treatment

Exclusion Criteria:

  • Positive history of known brain metastases or leptomeningeal disease (patients with brain metastases can only be enrolled if the following conditions are all met: treated and stable for >4 weeks [>2 weeks after SRS/Cyberknife]; no evidence for progression or hemorrhage after treatment; steroid treatment discontinued at least 2 weeks prior to first administration of doxorubicin; enzyme inducing anti-epileptic drugs discontinued at least 4 weeks before first administration of doxorubicin
  • History of hypersensitivity reaction to doxorubicin HCl or other components of DOXIL/CAELYX
  • Any major surgery, radiotherapy, or immunotherapy within the last 21 days (limited palliative radiation allowed >=2 weeks prior to the first dose; >=4 weeks for whole brain radiotherapy); chemotherapy regimens with delayed toxicity within the last 4 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
  • Use of an investigational drug within 21 days or 5 half-lives (whichever is shorter) prior to the first dose of doxorubicin
  • Unstable angina or myocardial infarction within the preceding 12 months; congestive heart failure or any history of uncontrolled cardiac disease >Class II based on New York Heart Association Criteria
  • Has an infection that is either an uncontrolled infection, clinically important (occurred within 4 weeks prior to first dose of study agent), or requiring current systemic intravenous treatment
  • Uncontrolled concurrent illness including, but not limited to, poorly controlled hypertension or diabetes, or psychiatric illness/social situation that may potentially impair patient's compliance with study procedures
  • Concomitant use of strong CYP3A4 inhibitors (such as clarithromycin, diltiazem, erythromycin, itraconazole, ketoconazole, nefazodone, ritonavir, telithromycin and verapamil) and strong CYP3A4 inducers (such as carbamazepine, phenobarbital, phenytoin, rifampin and St John's wort) from at least 4 weeks before the first dose of doxorubicin in Cycle 1 and until after completion of all pharmacokinetic sampling in Cycle 2
  • Has any condition that, in the opinion of the investigator, would make participation not be in the best interest (eg, compromise the well-being) of the patient or that could prevent, limit, or confound the protocol-specified assessments
  • Woman who is pregnant, or breast-feeding, or planning to become pregnant or is a man who plans to father a child while enrolled in this study or within 3 months after the last dose of study drug

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.
Experimental: Treatment A: DOXIL/CAELYX (doxorubicin)
50 mg/m2 of doxorubicin manufactured at the current site of manufacturing administered by IV infusion over 90 minutes on Day 1
Drug: DOXIL/CAELYX (doxorubicin) Treatment Sequence AB
Cycle 1 = Treatment A, Cycle 2 = Treatment B
Drug: DOXIL/CAELYX (doxorubicin) Treatment Sequence BA
Cycle 1 = Treatment B, Cycle 2 = Treatment A
Experimental: Treatment B: DOXIL/CAELYX (doxorubicin)
50 mg/m2 of doxorubicin manufactured at the new site of manufacturing (test product) administered by IV infusion over 90 minutes on Day 1
Drug: DOXIL/CAELYX (doxorubicin) Treatment Sequence AB
Cycle 1 = Treatment A, Cycle 2 = Treatment B
Drug: DOXIL/CAELYX (doxorubicin) Treatment Sequence BA
Cycle 1 = Treatment B, Cycle 2 = Treatment A

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
Time Frame
Maximum observed plasma concentration of encapsulated doxorubicin in participants with ovarian cancer
Time Frame: Predose Day 1 Cycles 1-2; Postdose Cycles 1-2 at 15 min, 30 min, 60 min, 90 min, 95 min, 105 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h, 48 h, 72 h, 96 h, 168 h, 336 h, 504 h, 672 h
Predose Day 1 Cycles 1-2; Postdose Cycles 1-2 at 15 min, 30 min, 60 min, 90 min, 95 min, 105 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h, 48 h, 72 h, 96 h, 168 h, 336 h, 504 h, 672 h
Area under the plasma-concentration-versus time curve from time 0 to time t of encapsulated doxorubicin in participants with ovarian cancer
Time Frame: Predose Day 1 Cycles 1-2; Postdose Cycles 1-2 at 15 min, 30 min, 60 min, 90 min, 95 min, 105 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h, 48 h, 72 h, 96 h, 168 h, 336 h, 504 h, 672 h
Predose Day 1 Cycles 1-2; Postdose Cycles 1-2 at 15 min, 30 min, 60 min, 90 min, 95 min, 105 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h, 48 h, 72 h, 96 h, 168 h, 336 h, 504 h, 672 h
Area under the plasma-concentration-versus time curve from time 0 to infinite time of encapsulated doxorubicin in participants with ovarian cancer
Time Frame: Predose Day 1 Cycles 1-2; Postdose Cycles 1-2 at 15 min, 30 min, 60 min, 90 min, 95 min, 105 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h, 48 h, 72 h, 96 h, 168 h, 336 h, 504 h, 672 h
Predose Day 1 Cycles 1-2; Postdose Cycles 1-2 at 15 min, 30 min, 60 min, 90 min, 95 min, 105 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h, 48 h, 72 h, 96 h, 168 h, 336 h, 504 h, 672 h

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
Number of participants affected by adverse events by MedDRA system organ class (SOC) and Preferred term (PT)
Time Frame: Up to 30 days after the last dose of study medication
Up to 30 days after the last dose of study medication
Maximum observed plasma concentration of free doxorubicin in participants with solid malignancies
Time Frame: Predose Day 1 Cycles 1-2; Postdose Cycles 1-2 at 15 min, 30 min, 60 min, 90 min, 95 min, 105 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h, 48 h, 72 h, 96 h, 168 h, 336 h, 504 h, 672 h
Predose Day 1 Cycles 1-2; Postdose Cycles 1-2 at 15 min, 30 min, 60 min, 90 min, 95 min, 105 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h, 48 h, 72 h, 96 h, 168 h, 336 h, 504 h, 672 h
Area under the plasma-concentration-versus time curve from time 0 to time t of free doxorubicin in participants with solid malignancies
Time Frame: Predose Day 1 Cycles 1-2; Postdose Cycles 1-2 at 15 min, 30 min, 60 min, 90 min, 95 min, 105 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h, 48 h, 72 h, 96 h, 168 h, 336 h, 504 h, 672 h
Predose Day 1 Cycles 1-2; Postdose Cycles 1-2 at 15 min, 30 min, 60 min, 90 min, 95 min, 105 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h, 48 h, 72 h, 96 h, 168 h, 336 h, 504 h, 672 h
Area under the plasma-concentration-versus time curve from time 0 to infinite time of free doxorubicin in participants with solid malignancies
Time Frame: Predose Day 1 Cycles 1-2; Postdose Cycles 1-2 at 15 min, 30 min, 60 min, 90 min, 95 min, 105 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h, 48 h, 72 h, 96 h, 168 h, 336 h, 504 h, 672 h
Predose Day 1 Cycles 1-2; Postdose Cycles 1-2 at 15 min, 30 min, 60 min, 90 min, 95 min, 105 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h, 48 h, 72 h, 96 h, 168 h, 336 h, 504 h, 672 h
Response
Time Frame: Up to Cycle 3 Day 1
Investigator determined response is defined by complete response, partial response or stable disease criteria
Up to Cycle 3 Day 1

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.
Janssen Research & Development, LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

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

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.
May 1, 2013

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.
December 1, 2014

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.
December 1, 2014

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).
March 14, 2013

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.
March 18, 2013

First Posted (Estimate)

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.
March 21, 2013

Study Record Updates

Last Update Posted (Estimate)

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.
December 4, 2015

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.
December 3, 2015

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.
December 1, 2015

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.
  • CR100961
  • DOXILNAP1002 (Other Identifier: Janssen Research & Development, LLC)
  • 2013-000376-15 (EudraCT Number)

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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