Back to resultsA Study of DOXIL/CAELYX in Patients With Advanced or Refractory Solid Malignancies Including Patients With Ovarian Cancer
Primary Purpose
Neoplasms
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
DOXIL/CAELYX reference product (Treatment A)
DOXIL/CAELYX test product (Treatment B)
Sponsored by
About this trial
This is an interventional treatment trial for Neoplasms focused on measuring Neoplasms, Neoplasms, Ovarian, Ovarian Cancer, Advanced or Refractory Solid Malignancies, Doxorubicin, DOXIL, CAELYX
Eligibility Criteria
Inclusion Criteria:
- Having advanced or refractory solid malignancies (histologically or cytologically confirmed advanced ovarian cancer failing platinum-based chemotherapy or metastatic breast cancer after failing approved life prolonging therapies or any solid malignancy that is metastatic or unresectable, and for which standard treatment is no longer an option)
- Eastern cooperative oncology group performance status 0 to 2
- Recovered from the acute toxicity (except alopecia and asymptomatic neuropathy) of any prior treatment
- Participants with prior doxorubicin (or other anthracyclines) or without any prior anthracylin exposure can also be included
- Agrees to protocol-defined use of effective contraception
Exclusion Criteria:
- Positive history of known brain metastases or leptomeningeal disease (spreading of cancer throughout the protective membranes covering the brain and spinal cord). Participants with brain metastases can only be enrolled if the following conditions are all met: 1) Brain metastases have been treated and stable for more than 4 weeks, 2) No evidence for progression or hemorrhage after treatment, 3) Steroid treatment was discontinued at least 2 weeks prior to first administration of DOXIL/CAELYX, and 4) Enzyme inducing anti-epileptic medicines were discontinued at least 4 weeks before first administration of DOXIL/CAELYX
- Use of an investigational medicine within 21 days or 5 half-lives (whichever is shorter) prior to the first dose of DOXIL/CAELYX
- Any major surgery, radiotherapy, or immunotherapy within the last 21 days. Chemotherapy regimens with delayed toxicity within the last 3 weeks (or within the last 6 weeks for prior nitrosourea or mitomycin C)
- Unstable angina or myocardial infarction within the preceding 12 months; congestive heart failure or any history of uncontrolled cardiac disease
- Having an uncontrolled infection and uncontrolled concurrent illness including, but not limited to, poorly controlled hypertension or diabetes, or psychiatric illness/social situation that may potentially impair the participant's compliance with study procedures
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Sequence AB
Sequence BA
Arm Description
Twenty-one participants will receive DOXIL/CAELYX reference product in Cycle 1 and DOXIL/CAELYX test product in Cycle 2. Each cycle will be separated by 28 days.
Twenty-one participants will receive DOXIL/CAELYX test product in Cycle 1 and DOXIL/CAELYX reference product in Cycle 2. Each cycle will be separated by 28 days.
Outcomes
Primary Outcome Measures
Maximum observed plasma concentration (Cmax) of encapsulated doxorubicin
Cmax is defined as the maximum observed analyte concentration.
Time to reach the maximum observed plasma concentration (Tmax) of encapsulated doxorubicin
Tmax is defined as the actual sampling time to reach maximum observed analyte concentration.
Area under the plasma concentration-time curve from time 0 to infinite time (AUC[0-infinity]) of encapsulated doxorubicin
AUC(0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of the Area Under the Curve (AUC) last and AUC(last)/lambda, in which AUC(last) is the last observed quantifiable concentration.
Secondary Outcome Measures
Maximum observed plasma concentration (Cmax) of free doxorubicin
Cmax is defined as maximum observed analyte concentration.
Time to reach the maximum observed plasma concentration (T max) of free doxorubicin
Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
Area under the plasma concentration-time curve from time 0 to infinite time (AUC[0 - infinity]) of free doxorubicin
AUC(0-infinity) is area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of Area under Curve (AUC) last and AUC(last)/lambda, in which AUC(last) is the last observed quantifiable concentration.
Number of participants with adverse events as a measure of safety and tolerability
Number of participants with response to the study medication at End-of-Treatment visit (Day 58)
The investigator will determine the response to the study medication as Complete Response (CR), Partial Response (PR) or Stable Disease (SD) according to the Response Evaluation Criteria in Solid Tumors (RECIST). As per the RECIST, CR is defined as the disappearance of all target and non-target lesions, PR is defined as 30% or more decrease in the sum of longest diameter of all target lesions from the baseline sum; and SD is defined as none of the CR and PR.
Full Information
NCT ID
NCT02081495
First Posted
March 5, 2014
Last Updated
November 10, 2016
Sponsor
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT02081495
Brief Title
A Study of DOXIL/CAELYX in Patients With Advanced or Refractory Solid Malignancies Including Patients With Ovarian Cancer
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
August 2014 (undefined)
Primary Completion Date
November 2015 (Actual)
Study Completion Date
November 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to support the qualification of a replacement manufacturing site for DOXIL/CAELYX.
Detailed Description
This is a randomized (study medication is assigned by chance), open-label (all people know the identity of the intervention), single dose, 2-cycle, crossover (method used to switch participants from one treatment arm to another in a clinical study), and bioequivalence (biological equivalence of two formulations of a study medication) study of DOXIL/CAELYX in participants with advanced or refractory solid malignancies (including at least 24 participants 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 participants with ovarian cancer. An interim analysis of free doxorubicin will be performed at the end of Stage 1 using data from 42 participants of all cancer types. The study may continue into Stage 2 with additional participants 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 (within 28 days before the first study medication administration) followed by the treatment phase consisting of 2 doxorubicin treatment cycles (28 days each) and an end-of-treatment visit on Day 58. Participants may enter an optional extension phase after 2 cycles. Safety will be evaluated by the assessment of adverse events, vital signs, 12-lead electrocardiogram, clinical laboratory testing, and left ventricular ejection fraction (measurement of the percentage of blood leaving the heart each time when it contracts) 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasms
Keywords
Neoplasms, Neoplasms, Ovarian, Ovarian Cancer, Advanced or Refractory Solid Malignancies, Doxorubicin, DOXIL, CAELYX
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sequence AB
Arm Type
Experimental
Arm Description
Twenty-one participants will receive DOXIL/CAELYX reference product in Cycle 1 and DOXIL/CAELYX test product in Cycle 2. Each cycle will be separated by 28 days.
Arm Title
Sequence BA
Arm Type
Experimental
Arm Description
Twenty-one participants will receive DOXIL/CAELYX test product in Cycle 1 and DOXIL/CAELYX reference product in Cycle 2. Each cycle will be separated by 28 days.
Intervention Type
Drug
Intervention Name(s)
DOXIL/CAELYX reference product (Treatment A)
Other Intervention Name(s)
DOXIL, CAELYX
Intervention Description
Participants will receive DOXIL/CAELYX reference product 50 mg/m2 as an intravenous (into a vein) infusion over 90 minutes on Day 1.
Intervention Type
Drug
Intervention Name(s)
DOXIL/CAELYX test product (Treatment B)
Other Intervention Name(s)
DOXIL, CAELYX
Intervention Description
Participants will receive DOXIL/CAELYX test product 50 mg/m2 as an intravenous infusion over 90 minutes on Day 1.
Primary Outcome Measure Information:
Title
Maximum observed plasma concentration (Cmax) of encapsulated doxorubicin
Description
Cmax is defined as the maximum observed analyte concentration.
Time Frame
Predose, and postdose Day 1 (Minutes 15, 30, 60, 90, 95, 105; Hours 2, 3, 4, 6, 8), Days 2, 3, 4, 5, 8, 15, 22, and 26 (for Cycles 1 and 2)
Title
Time to reach the maximum observed plasma concentration (Tmax) of encapsulated doxorubicin
Description
Tmax is defined as the actual sampling time to reach maximum observed analyte concentration.
Time Frame
Predose, and postdose Day 1 (Minutes 15, 30, 60, 90, 95, 105; Hours 2, 3, 4, 6, 8), Days 2, 3, 4, 5, 8, 15, 22, and 26 (for Cycles 1 and 2)
Title
Area under the plasma concentration-time curve from time 0 to infinite time (AUC[0-infinity]) of encapsulated doxorubicin
Description
AUC(0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of the Area Under the Curve (AUC) last and AUC(last)/lambda, in which AUC(last) is the last observed quantifiable concentration.
Time Frame
Predose, and postdose Day 1 (Minutes 15, 30, 60, 90, 95, 105; Hours 2, 3, 4, 6, 8), Days 2, 3, 4, 5, 8, 15, 22, and 26 (for Cycles 1 and 2)
Secondary Outcome Measure Information:
Title
Maximum observed plasma concentration (Cmax) of free doxorubicin
Description
Cmax is defined as maximum observed analyte concentration.
Time Frame
Predose, and postdose Day 1 (Minutes 15, 30, 60, 90, 95, 105; Hours 2, 3, 4, 6, 8), Days 2, 3, 4, 5, 8, 15, 22, and 26 (for Cycles 1 and 2)
Title
Time to reach the maximum observed plasma concentration (T max) of free doxorubicin
Description
Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
Time Frame
Predose, and postdose Day 1 (Minutes 15, 30, 60, 90, 95, 105; Hours 2, 3, 4, 6, 8), Days 2, 3, 4, 5, 8, 15, 22, and 26 (for Cycles 1 and 2)
Title
Area under the plasma concentration-time curve from time 0 to infinite time (AUC[0 - infinity]) of free doxorubicin
Description
AUC(0-infinity) is area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of Area under Curve (AUC) last and AUC(last)/lambda, in which AUC(last) is the last observed quantifiable concentration.
Time Frame
Predose, and postdose Day 1 (Minutes 15, 30, 60, 90, 95, 105; Hours 2, 3, 4, 6, 8), Days 2, 3, 4, 5, 8, 15, 22, and 26 (for Cycles 1 and 2)
Title
Number of participants with adverse events as a measure of safety and tolerability
Time Frame
Up to Day 86
Title
Number of participants with response to the study medication at End-of-Treatment visit (Day 58)
Description
The investigator will determine the response to the study medication as Complete Response (CR), Partial Response (PR) or Stable Disease (SD) according to the Response Evaluation Criteria in Solid Tumors (RECIST). As per the RECIST, CR is defined as the disappearance of all target and non-target lesions, PR is defined as 30% or more decrease in the sum of longest diameter of all target lesions from the baseline sum; and SD is defined as none of the CR and PR.
Time Frame
Day 58 or 30 days after the last dose of the study medication for early withdrawal participants
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Having advanced or refractory solid malignancies (histologically or cytologically confirmed advanced ovarian cancer failing platinum-based chemotherapy or metastatic breast cancer after failing approved life prolonging therapies or any solid malignancy that is metastatic or unresectable, and for which standard treatment is no longer an option)
Eastern cooperative oncology group performance status 0 to 2
Recovered from the acute toxicity (except alopecia and asymptomatic neuropathy) of any prior treatment
Participants with prior doxorubicin (or other anthracyclines) or without any prior anthracylin exposure can also be included
Agrees to protocol-defined use of effective contraception
Exclusion Criteria:
Positive history of known brain metastases or leptomeningeal disease (spreading of cancer throughout the protective membranes covering the brain and spinal cord). Participants with brain metastases can only be enrolled if the following conditions are all met: 1) Brain metastases have been treated and stable for more than 4 weeks, 2) No evidence for progression or hemorrhage after treatment, 3) Steroid treatment was discontinued at least 2 weeks prior to first administration of DOXIL/CAELYX, and 4) Enzyme inducing anti-epileptic medicines were discontinued at least 4 weeks before first administration of DOXIL/CAELYX
Use of an investigational medicine within 21 days or 5 half-lives (whichever is shorter) prior to the first dose of DOXIL/CAELYX
Any major surgery, radiotherapy, or immunotherapy within the last 21 days. Chemotherapy regimens with delayed toxicity within the last 3 weeks (or within the last 6 weeks for prior nitrosourea or mitomycin C)
Unstable angina or myocardial infarction within the preceding 12 months; congestive heart failure or any history of uncontrolled cardiac disease
Having an uncontrolled infection and uncontrolled concurrent illness including, but not limited to, poorly controlled hypertension or diabetes, or psychiatric illness/social situation that may potentially impair the participant's compliance with study procedures
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
Los Angeles
State/Province
California
Country
United States
City
Brussel
Country
Belgium
City
Wilrijk
Country
Belgium
City
Edmonton
State/Province
Alberta
Country
Canada
City
Barcelona
Country
Spain
City
Madrid
Country
Spain
12. IPD Sharing Statement
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_7051&studyid=6195&filename=CR103500_CSR.pdf
Description
A Pivotal Bioequivalence Study of DOXIL®/CAELYX® Manufactured at a New Site in Subjects with Advanced or Refractory Solid Malignancies
Learn more about this trial
A Study of DOXIL/CAELYX in Patients With Advanced or Refractory Solid Malignancies Including Patients With Ovarian Cancer
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