Back to resultsA Pivotal Bioequivalence Study of DOXIL/CAELYX (Doxorubicin HCL) in Patients With Advanced or Refractory Solid Malignancies Including Patients With Ovarian Cancer
Primary Purpose
Neoplasms, Neoplasms, Ovarian, Neoplasms, Breast
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
DOXIL/CAELYX (doxorubicin) Treatment Sequence AB
DOXIL/CAELYX (doxorubicin) Treatment Sequence BA
Sponsored by
About this trial
This is an interventional treatment trial for Neoplasms focused on measuring Ovarian cancer, Breast cancer, Solid malignancy, Advanced or refractory solid malignancy, Metastatic cancer, DOXIL/CAELYX, Doxorubicin HCL, Bioequivalence
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Treatment A: DOXIL/CAELYX (doxorubicin)
Treatment B: DOXIL/CAELYX (doxorubicin)
Arm Description
50 mg/m2 of doxorubicin manufactured at the current site of manufacturing administered by IV infusion over 90 minutes on Day 1
50 mg/m2 of doxorubicin manufactured at the new site of manufacturing (test product) administered by IV infusion over 90 minutes on Day 1
Outcomes
Primary Outcome Measures
Maximum observed plasma concentration of encapsulated doxorubicin in participants with ovarian cancer
Area under the plasma-concentration-versus time curve from time 0 to time t of encapsulated doxorubicin in participants with ovarian cancer
Area under the plasma-concentration-versus time curve from time 0 to infinite time of encapsulated doxorubicin in participants with ovarian cancer
Secondary Outcome Measures
Maximum observed plasma concentration of free doxorubicin in participants with solid malignancies
Area under the plasma-concentration-versus time curve from time 0 to time t of free doxorubicin in participants with solid malignancies
Area under the plasma-concentration-versus time curve from time 0 to infinite time of free doxorubicin in participants with solid malignancies
Number of participants affected by adverse events by MedDRA system organ class (SOC) and Preferred term (PT)
Response
Investigator determined response is defined by complete response, partial response or stable disease criteria
Full Information
NCT ID
NCT01815294
First Posted
March 14, 2013
Last Updated
December 3, 2015
Sponsor
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT01815294
Brief Title
A Pivotal Bioequivalence Study of DOXIL/CAELYX (Doxorubicin HCL) 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
December 2015
Overall Recruitment Status
Completed
Study Start Date
May 2013 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (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 (doxorubicin HCL).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasms, Neoplasms, Ovarian, Neoplasms, Breast, Advanced or Refractory Solid Malignancies
Keywords
Ovarian cancer, Breast cancer, Solid malignancy, Advanced or refractory solid malignancy, Metastatic cancer, DOXIL/CAELYX, Doxorubicin HCL, Bioequivalence
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
54 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment A: DOXIL/CAELYX (doxorubicin)
Arm Type
Experimental
Arm Description
50 mg/m2 of doxorubicin manufactured at the current site of manufacturing administered by IV infusion over 90 minutes on Day 1
Arm Title
Treatment B: DOXIL/CAELYX (doxorubicin)
Arm Type
Experimental
Arm Description
50 mg/m2 of doxorubicin manufactured at the new site of manufacturing (test product) administered by IV infusion over 90 minutes on Day 1
Intervention Type
Drug
Intervention Name(s)
DOXIL/CAELYX (doxorubicin) Treatment Sequence AB
Intervention Description
Cycle 1 = Treatment A, Cycle 2 = Treatment B
Intervention Type
Drug
Intervention Name(s)
DOXIL/CAELYX (doxorubicin) Treatment Sequence BA
Intervention Description
Cycle 1 = Treatment B, Cycle 2 = Treatment A
Primary Outcome Measure Information:
Title
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
Title
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
Title
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
Secondary Outcome Measure Information:
Title
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
Title
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
Title
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
Title
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
Title
Response
Description
Investigator determined response is defined by complete response, partial response or stable disease criteria
Time Frame
Up to Cycle 3 Day 1
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
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
Nashville
State/Province
Tennessee
Country
United States
City
San Antonio
State/Province
Texas
Country
United States
City
Brussel
Country
Belgium
City
Wilrijk
Country
Belgium
City
Barcelona
Country
Spain
City
Madrid
Country
Spain
City
Valencia
Country
Spain
City
London
Country
United Kingdom
12. IPD Sharing Statement
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_7051&studyid=3629&filename=CR100961_CSR.pdf
Description
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
Learn more about this trial
A Pivotal Bioequivalence Study of DOXIL/CAELYX (Doxorubicin HCL) in Patients With Advanced or Refractory Solid Malignancies Including Patients With Ovarian Cancer
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