The purpose of this study is to support the qualification of a replacement manufacturing site for DOXIL/CAELYX.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
35
Participants will receive DOXIL/CAELYX reference product 50 mg/m2 as an intravenous (into a vein) infusion over 90 minutes on Day 1.
Participants will receive DOXIL/CAELYX test product 50 mg/m2 as an intravenous infusion over 90 minutes on Day 1.
Unnamed facility
Los Angeles, California, United States
Unnamed facility
Brussels, Belgium
Unnamed facility
Wilrijk, Belgium
Unnamed facility
Edmonton, Alberta, Canada
Unnamed facility
Barcelona, Spain
Maximum observed plasma concentration (Cmax) of encapsulated doxorubicin
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)
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.
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)
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.
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)
Maximum observed plasma concentration (Cmax) of free doxorubicin
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)
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.
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)
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Unnamed facility
Madrid, Spain
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.
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)
Number of participants with adverse events as a measure of safety and tolerability
Time frame: Up to Day 86
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.
Time frame: Day 58 or 30 days after the last dose of the study medication for early withdrawal participants