NeoplasmsPhase 1NCT02081495
A Study of DOXIL/CAELYX in Patients With Advanced or Refractory Solid Malignancies Including Patients With Ovarian Cancer
A Phase 1 study testing DOXIL/CAELYX reference product (Treatment A) and DOXIL/CAELYX test product (Treatment B) in people with Neoplasms, run by Janssen Research & Development, LLC at 6 sites in 4 countries.
Trial summary
The purpose of this study is to support the qualification of a replacement manufacturing site for DOXIL/CAELYX. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- DOXIL/CAELYX reference product (Treatment A) and DOXIL/CAELYX test product (Treatment B)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 6 sitesin 4 countries
- Study dates
- Aug 2014to Nov 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
6 sites in 4 countries.
6 sites in 4 countries
About this study
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
The purpose of this study is to support the qualification of a replacement manufacturing site for DOXIL/CAELYX.
Read the 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.
- Conditions
- Neoplasms
- Being tested
- DOXIL/CAELYX reference product (Treatment A), DOXIL/CAELYX test product (Treatment B)
- Keywords
- Neoplasms, Neoplasms, Ovarian, Ovarian Cancer, Advanced or Refractory Solid Malignancies, Doxorubicin, DOXIL, CAELYX
- Medical subject headings
- Neoplasms, Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DOXIL/CAELYX reference product (Treatment A)Drug
Also called DOXIL, CAELYX
Participants will receive DOXIL/CAELYX reference product 50 mg/m2 as an intravenous (into a vein) infusion over 90 minutes on Day 1.
DOXIL/CAELYX test product (Treatment B)Drug
Also called DOXIL, CAELYX
Participants will receive DOXIL/CAELYX test product 50 mg/m2 as an intravenous infusion over 90 minutes on Day 1.
| Study group | Role | What they receive |
|---|---|---|
| Sequence AB | Experimental | 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. Receives: Drug: DOXIL/CAELYX reference product (Treatment A); Drug: DOXIL/CAELYX test product (Treatment B) |
| Sequence BA | Experimental | 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. Receives: Drug: DOXIL/CAELYX reference product (Treatment A); Drug: DOXIL/CAELYX test product (Treatment B) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum observed plasma concentration (Cmax) of encapsulated doxorubicin
Cmax is defined as the maximum observed analyte concentration.
Measured: 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.
Measured: 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.
Measured: 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 outcomes (5)
Maximum observed plasma concentration (Cmax) of free doxorubicin
Cmax is defined as maximum observed analyte concentration.
Measured: 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.
Measured: 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 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.
Measured: 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
Measured: 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.
Measured: Day 58 or 30 days after the last dose of the study medication for early withdrawal participants
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2014 (estimated)
- Study startAug 2014
- Primary completionNov 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02081495
- Sponsor's protocol ID
- CR103500
- Other IDs
- DOXILNAP1004, 2013-004641-16
- Status last verified
- Oct 2016
- First submitted
- 5 Mar 2014
- Last updated
- 11 Nov 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02081495
- Acronym / sponsor ID
- CR103500
- Conditions
- Neoplasms
- Keywords
- Neoplasms, Neoplasms, Ovarian, Ovarian Cancer, Advanced or Refractory Solid Malignancies, Doxorubicin, DOXIL, CAELYX
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- Aug 2014
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 7 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sequence AB | Experimental | Drug: DOXIL/CAELYX reference product (Treatment A), Drug: DOXIL/CAELYX test product (Treatment B)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. |
| Sequence BA | Experimental | Drug: DOXIL/CAELYX reference product (Treatment A), Drug: DOXIL/CAELYX test product (Treatment B)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DOXIL/CAELYX reference product (Treatment A)Also: DOXIL, CAELYXParticipants will receive DOXIL/CAELYX reference product 50 mg/m2 as an intravenous (into a vein) infusion over 90 minutes on Day 1. | Drug | Sequence AB, Sequence BA |
| DOXIL/CAELYX test product (Treatment B)Also: DOXIL, CAELYXParticipants will receive DOXIL/CAELYX test product 50 mg/m2 as an intravenous infusion over 90 minutes on Day 1. | Drug | Sequence AB, Sequence BA |
Primary outcome
Maximum observed plasma concentration (Cmax) of encapsulated doxorubicin
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)
Cmax is defined as the maximum observed analyte concentration.
Time to reach the maximum observed plasma concentration (Tmax) of encapsulated doxorubicin
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)
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
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)
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.
5 secondary outcomes
Maximum observed plasma concentration (Cmax) of free doxorubicin
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
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 free doxorubicin
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)
Time frame: Day 58 or 30 days after the last dose of the study medication for early withdrawal participants
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Nov 2016.
- A Pivotal Bioequivalence Study of DOXIL®/CAELYX® Manufactured at a New Site in Subjects with Advanced or Refractory Solid MalignanciesLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
6 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DOXIL/CAELYX reference product (Treatment A) and DOXIL/CAELYX test product (Treatment B) in people with Neoplasms, run by Janssen Research & Development, LLC at 6 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Belgium, Spain, United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum observed plasma concentration (Cmax) of encapsulated doxorubicin (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)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Nov 2016.