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An Efficacy and Safety Study for Yondelis (Trabectedin) in Patients With Advanced Relapsed Ovarian Cancer

Sponsor
Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Industry)
Overall Status
Completed
CT.gov ID
NCT00113607
Collaborator
PharmaMar (Industry)
672
Enrollment
113
Locations
2
Arms
67
Duration (Months)
5.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is to compare the progression-free survival (PFS) of the combination of trabectedin + DOXIL with DOXIL monotherapy in patients with ovarian cancer.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

This is a multicenter, open-label (all people know the identity of the intervention), randomized (study medication is assigned by chance), Phase 3 study comparing the combination of trabectedin + DOXIL with DOXIL monotherapy in patients with advanced ovarian cancer (who were previously treated and for whom first-line platinum-based chemotherapy regimen has failed). Approximately 650 patients will be randomly assigned to 1 of the treatment arms (DOXIL and DOXIL + trabectedin) over 2 years. At the time of randomization, patients will be stratified on the basis of platinum sensitivity of disease (sensitive or resistant) and baseline Eastern Cooperative Oncology Group performance status score (0 to 1 or 2. Safety will be evaluated on the basis of adverse events, clinical laboratory tests, physical examination, vital signs assessment and cardiovascular safety assessment. An interim analysis of overall survival will be performed in conjunction with progression-free survival analysis during the study. Treatment will be continued until disease progression occurred or until patients experienced a confirmed complete response for at least 2 cycles. Continuation of treatment in select individual patients beyond this study end date will be allowed if the investigator determined that the patient is benefiting from treatment, is eligible to receive further therapy, and consents to treatment. If disease progression has not occurred at treatment termination, then disease assessment will continue every 8 weeks until there is evidence of disease progression or death, or until the clinical data cutoff date, or until the start of first subsequent anticancer therapy, whichever is earlier.

Study Design

Study Type:
Interventional
Actual Enrollment :
672 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-Label Multicenter Randomized Phase 3 Study Comparing the Combination of DOXIL/CAELYX and YONDELIS With DOXIL/CAELYX Alone in Subjects With Advanced Relapsed Ovarian Cancer
Study Start Date :
Apr 1, 2005
Actual Primary Completion Date :
Nov 1, 2010
Actual Study Completion Date :
Nov 1, 2010

Arms and Interventions

Arm Intervention/Treatment
Experimental: DOXIL + trabectedin

Combination arm - Trabectedin + DOXIL: DOXIL 30 mg/m2 intravenous (IV) infusion over 90 minutes + trabectedin 1.1 mg/m2 IV infusion over 3 hours every 3 weeks. patients will be premedicated with 20 mg dexamethasone or its equivalent IV infusion over 30 minutes prior to the DOXIL infusion.

Drug: Trabectedin
Type=exact number, unit=mg/m2, number=1.1, form=solution, route=IV. Trabectedin will be administered over 3 hours every 3 weeks.
Other Names:
  • Yondelis

    • Drug: DOXIL
    Type=exact number, unit=mg/m2, number=30, 50, form=solution, route=IV. DOXIL will be administered over 90 minutes every 4 weeks when administered alone (monotherapy) and every 3 weeks when administered with trabectedin.
    Other Names:
  • CAELYX

    • Drug: Dexamethasone
    Type=exact number, unit=mg, number=20, form=solution, route=IV. Dexamethasone or its equivalent will be administered over 30 minutes prior to the DOXIL infusion.
    Active Comparator: DOXIL

    Monotherapy arm - DOXIL: 50 mg/m2 IV infusion over 90 minutes every 4 weeks.

    Drug: DOXIL
    Type=exact number, unit=mg/m2, number=30, 50, form=solution, route=IV. DOXIL will be administered over 90 minutes every 4 weeks when administered alone (monotherapy) and every 3 weeks when administered with trabectedin.
    Other Names:
  • CAELYX

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Progression-Free Survival (PFS): Independent Radiologist Review [From the date of randomization until the date of disease progression or death, as assessed for approximately 3 years]

      PFS is defined as the time between randomization and disease progression or death.

    Secondary Outcome Measures

    1. Overall Survival [From the date of randomization until the date of death, as assessed for approximately 3 years]

      Overall survival was defined as the time between the randomization and death

    2. Objective Response Rate (ORR) - Independent Radiologist Review [From the date of randomization until the date of disease progression or death, as assessed for approximately 3 years]

      Percentage of participants who achieved complete response (CR) or partial response (PR) as best overall response. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR)= greater than or equal to 30% decrease in the sum of the longest diameter of target lesions and Overall Response (OR) = CR + PR.

    3. Duration of Response: Independent Radiologist Review [From the date of first documentation of response to the date of disease progression or death due to progressive disease, as assessed for approximately 3 years]

      Duration of response was defined only for participants who had complete response or partial response as best overall response. Duration of response was calculated from the date of first documentation of response (not the confirmation) to the date of disease progression or death due to progressive disease.

    4. Median Area Under Curve (AUC) of Trabectedin. [Day 1 (Predose; 1.5 hour after start of infusion; 5 minutes, 2 hour and 6 to 20 hour after end of infusion); Day 8 (168 hour after end of infusion); and Day 15 (336 hour after end of infusion) at Cycles 1 and 2]

      Median simulated area under the curve (AUC) of a 21 day trabectedin profile of participants (of this study) administering trabectedin and doxil, calculated using the trapezoidal rule method. Simulations were based on a dataset created of 1000 participants using the posthoc parameter estimations, derived from the population pharmacokinetic analysis dataset of Trabectedin (Participants=831, with resampling). Plasma concentration-time profiles were simulated up to 504 hour post-dosing using a rich sampling.

    5. Median Maximum Plasma Concentration (Cmax) of Trabectedin. [Day 1 (Predose; 1.5 hour after start of infusion; 5 minutes, 2 hour and 6 to 20 hour after end of infusion); Day 8 (168 hour after end of infusion); and Day 15 (336 hour after end of infusion) at Cycles 1 and 2]

      Median simulated maximum plasma concentration (Cmax) at 3 hour of a 21 day trabectedin profile of participants (of this study) administering trabectedin and doxil. The assessment of Cmax was based on a dataset created of 1000 participants using the posthoc parameter estimations, derived from the population pharmacokinetic analysis dataset of Trabectedin (participants=831, with resampling). Plasma concentration-time profiles were simulated up to 504 hour post-dosing using a rich sampling.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Histologically proven epithelial ovarian cancer, epithelial fallopian tube cancer, or primary peritoneal cancer

    • Prior treatment with only 1 platinum based chemotherapy regimen

    • Eastern Cooperative Oncology Group status of not more than 2

    • Progression more than 6 months after the start of initial chemotherapy treatment

    Exclusion Criteria:

    • Treatment with more than 1 prior chemotherapy regimen

    • Progression within 6 months after starting initial chemotherapy

    • Prior exposure to anthracyclines

    • Unwilling or unable to have central venous catheter

    • Known clinically relevant central nervous system metastasis

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mobile Alabama United States
    2 Tucson Arizona United States
    3 Los Angeles California United States
    4 Newport Beach California United States
    5 Orange California United States
    6 Englewood Colorado United States
    7 Stamford Connecticut United States
    8 Tampa Florida United States
    9 Coeur D Alene Idaho United States
    10 Louisville Kentucky United States
    11 New Orleans Louisiana United States
    12 Boston Massachusetts United States
    13 Minneapolis Minnesota United States
    14 Saint Louis Missouri United States
    15 Morristown New Jersey United States
    16 New York New York United States
    17 Charlotte North Carolina United States
    18 Greenville North Carolina United States
    19 Winston Salem North Carolina United States
    20 Cleveland Ohio United States
    21 Toledo Ohio United States
    22 Portland Oregon United States
    23 Pittsburgh Pennsylvania United States
    24 Greenville South Carolina United States
    25 Chattanooga Tennessee United States
    26 Nashville Tennessee United States
    27 Dallas Texas United States
    28 Galveston Texas United States
    29 Buenos Aires Argentina
    30 Mendoza Argentina
    31 Sante Fe Argentina
    32 Adelaide Australia
    33 Bentleigh Australia
    34 Douglas Australia
    35 St Leonards Australia
    36 Toorak Gardens Australia
    37 Edegem Belgium
    38 Hasselt Belgium
    39 Leuven Belgium
    40 Wilrijk Belgium
    41 Barretos Brazil
    42 Belo Horizonte Brazil
    43 Cerqueira Cesar Brazil
    44 Londrina Brazil
    45 Santo Andre Brazil
    46 Sao Paulo Brazil
    47 Calgary Alberta Canada
    48 Edmonton Alberta Canada
    49 Ottawa Ontario Canada
    50 Montreal Quebec Canada
    51 Quebec City Quebec Canada
    52 Reneca Chile
    53 Santiago Chile
    54 Beijing China
    55 Guangzhou China
    56 Hangzhou China
    57 Jinan China
    58 Shanghai China
    59 Chartres France
    60 Paris France
    61 Pierre Benite Cedex France
    62 Düsseldorf Germany
    63 Heidelberg Germany
    64 Jena Germany
    65 Karlsruhe Germany
    66 Mainz Germany
    67 Villingen-Schwenningen Germany
    68 Wilhelmshaven Germany
    69 Chai Wan Hong Kong
    70 Hong Kong Hong Kong
    71 Sha Tin Hong Kong
    72 Seoul Korea, Republic of
    73 Amsterdam Netherlands
    74 Enschede Netherlands
    75 Groningen Netherlands
    76 Maastricht Netherlands
    77 Gdansku Poland
    78 Gliwice Poland
    79 Krakow Poland
    80 Olsztyn Poland
    81 Poznan Poland
    82 Warszawa Poland Poland
    83 Wroclaw Poland
    84 Chelyabinsk Russian Federation
    85 Moscow N/A Russian Federation
    86 Moscow Russian Federation
    87 Obninsk, Kaluga Region Russian Federation
    88 Orenburg Russian Federation
    89 Saint Petersburg Russian Federation
    90 Samara Russian Federation
    91 St. Petersburg Russian Federation
    92 Singapore Singapore
    93 Barcelona Spain
    94 Girona Spain
    95 Guadalajara Spain
    96 L'Hospitalet De Llobregat Spain
    97 Madrid Spain
    98 Maranon Spain
    99 Valencia Spain
    100 Zaragoza Spain
    101 Göteborg Sweden
    102 Umeå Sweden
    103 Uppsala Sweden
    104 Kaohsiung County Taiwan
    105 Taipei Taiwan
    106 Tao-Yuan Taiwan
    107 Birmingham United Kingdom
    108 Edinburgh United Kingdom
    109 Leicester United Kingdom
    110 London United Kingdom
    111 Nottingham United Kingdom
    112 Poole United Kingdom
    113 Sheffield United Kingdom

    Sponsors and Collaborators

    • Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
    • PharmaMar

    Investigators

    • Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
    ClinicalTrials.gov Identifier:
    NCT00113607
    Other Study ID Numbers:
    • CR003448
    • ET743-OVA-301
    • 2004-005276-16
    First Posted:
    Jun 10, 2005
    Last Update Posted:
    Jun 27, 2014
    Last Verified:
    Jun 1, 2014
    Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
    Ovarian cancer
    Trabectedin
    Yondelis
    Advanced Relapsed Ovarian Cancer
    DOXIL
    CAELYX
    Additional relevant MeSH terms:
    Ovarian Neoplasms
    Carcinoma, Ovarian Epithelial
    Dexamethasone
    Trabectedin

    Study Results

    Participant Flow

    Recruitment Details This study was conducted in a total of 21 countries at 124 sites worldwide.
    Pre-assignment Detail 672 participants were randomized (337 in trabectedin + DOXIL arm and 335 in DOXIL arm) and out of which 9 participants were not treated. 663 participants received treatment ie, 330 participants received DOXIL and 333 received trabectedin + DOXIL.
    Arm/Group Title DOXIL Trabectedin/DOXIL
    Arm/Group Description 50 mg/m2 DOXIL administered as a 90-minute intravenous (IV) infusion, every 4 weeks 30 mg/m2 DOXIL administered as a 90-minute IV infusion followed by 1.1 mg/m2 trabectedin as a 3-hour IV infusion, every 3 weeks
    Period Title: Overall Study
    STARTED 335 337
    COMPLETED 0 0
    NOT COMPLETED 335 337

    Baseline Characteristics

    Arm/Group Title DOXIL Trabectedin/DOXIL Total
    Arm/Group Description 50 mg/m2 DOXIL administered as a 90-minute intravenous (IV) infusion, every 4 weeks 30 mg/m2 DOXIL administered as a 90-minute IV infusion followed by 1.1 mg/m2 trabectedin as a 3-hour IV infusion, every 3 weeks Total of all reporting groups
    Overall Participants 335 337 672
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    58.2
    (10.75)
    56.8
    (10.48)
    57.5
    (10.63)
    Sex: Female, Male (Count of Participants)
    Female
    335
    100%
    337
    100%
    672
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    Argentina
    5
    1.5%
    2
    0.6%
    7
    1%
    Australia
    5
    1.5%
    2
    0.6%
    7
    1%
    Belgium-Luxemburg
    12
    3.6%
    13
    3.9%
    25
    3.7%
    Brazil
    12
    3.6%
    9
    2.7%
    21
    3.1%
    Canada
    22
    6.6%
    34
    10.1%
    56
    8.3%
    Chile
    1
    0.3%
    2
    0.6%
    3
    0.4%
    France
    0
    0%
    2
    0.6%
    2
    0.3%
    Germany
    6
    1.8%
    13
    3.9%
    19
    2.8%
    Hong Kong
    10
    3%
    15
    4.5%
    25
    3.7%
    Italy
    3
    0.9%
    4
    1.2%
    7
    1%
    Netherlands
    4
    1.2%
    1
    0.3%
    5
    0.7%
    China
    37
    11%
    36
    10.7%
    73
    10.9%
    Poland
    47
    14%
    39
    11.6%
    86
    12.8%
    Republic Of Korea
    17
    5.1%
    11
    3.3%
    28
    4.2%
    Russia
    52
    15.5%
    56
    16.6%
    108
    16.1%
    Singapore
    0
    0%
    1
    0.3%
    1
    0.1%
    Spain
    8
    2.4%
    9
    2.7%
    17
    2.5%
    Sweden
    6
    1.8%
    8
    2.4%
    14
    2.1%
    Taiwan
    7
    2.1%
    2
    0.6%
    9
    1.3%
    United Kingdom
    18
    5.4%
    20
    5.9%
    38
    5.7%
    United States Of America
    63
    18.8%
    58
    17.2%
    121
    18%

    Outcome Measures

    1. Primary Outcome
    Title Progression-Free Survival (PFS): Independent Radiologist Review
    Description PFS is defined as the time between randomization and disease progression or death.
    Time Frame From the date of randomization until the date of disease progression or death, as assessed for approximately 3 years

    Outcome Measure Data

    Analysis Population Description
    All Measurable Analysis Participants: All randomized participants who had measurable disease at baseline as assessed by the independent radiology review. Measurable disease is defined as having at least 1 lesion measured with a diameter of ≥20 mm using conventional techniques or of ≥10 mm using a spiral computerized tomography scan.
    Arm/Group Title DOXIL Trabectedin/DOXIL
    Arm/Group Description 50 mg/m2 DOXIL administered as a 90-minute intravenous (IV) infusion, every 4 weeks 30 mg/m2 DOXIL administered as a 90-minute IV infusion followed by 1.1 mg/m2 trabectedin as a 3-hour IV infusion, every 3 weeks
    Measure Participants 317 328
    Median (95% Confidence Interval) [Months]
    5.8
    7.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection DOXIL, Trabectedin/DOXIL
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0190
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio, log
    Estimated Value 0.79
    Confidence Interval (2-Sided) 95%
    0.65 to 0.96
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Overall Survival
    Description Overall survival was defined as the time between the randomization and death
    Time Frame From the date of randomization until the date of death, as assessed for approximately 3 years

    Outcome Measure Data

    Analysis Population Description
    All Randomized Analysis Participants: all participants who were randomized to this study, independent of whether they received study medication or not
    Arm/Group Title DOXIL Trabectedin/DOXIL
    Arm/Group Description 50 mg/m2 DOXIL administered as a 90-minute intravenous (IV) infusion, every 4 weeks 30 mg/m2 DOXIL administered as a 90-minute IV infusion followed by 1.1 mg/m2 trabectedin as a 3-hour IV infusion, every 3 weeks
    Measure Participants 335 337
    Median (95% Confidence Interval) [Months]
    18.9
    22.2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection DOXIL, Trabectedin/DOXIL
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0835
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio, log
    Estimated Value 0.86
    Confidence Interval (2-Sided) 95%
    0.72 to 1.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Objective Response Rate (ORR) - Independent Radiologist Review
    Description Percentage of participants who achieved complete response (CR) or partial response (PR) as best overall response. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR)= greater than or equal to 30% decrease in the sum of the longest diameter of target lesions and Overall Response (OR) = CR + PR.
    Time Frame From the date of randomization until the date of disease progression or death, as assessed for approximately 3 years

    Outcome Measure Data

    Analysis Population Description
    All Randomized Analysis Participants: all participants who were randomized to this study, independent of whether they received study medication or not.
    Arm/Group Title DOXIL Trabectedin/DOXIL
    Arm/Group Description 50 mg/m2 DOXIL administered as a 90-minute intravenous (IV) infusion, every 4 weeks 30 mg/m2 DOXIL administered as a 90-minute IV infusion followed by 1.1 mg/m2 trabectedin as a 3-hour IV infusion, every 3 weeks
    Measure Participants 335 337
    Number [Percentage of participants]
    18.8
    5.6%
    27.6
    8.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection DOXIL, Trabectedin/DOXIL
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0080
    Comments
    Method Fisher Exact
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.646
    Confidence Interval (2-Sided) 95%
    1.144 to 2.367
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Duration of Response: Independent Radiologist Review
    Description Duration of response was defined only for participants who had complete response or partial response as best overall response. Duration of response was calculated from the date of first documentation of response (not the confirmation) to the date of disease progression or death due to progressive disease.
    Time Frame From the date of first documentation of response to the date of disease progression or death due to progressive disease, as assessed for approximately 3 years

    Outcome Measure Data

    Analysis Population Description
    All Responders (CR/PR) Analysis Participants: all participants who achieved CR or PR as best overall response during the study.
    Arm/Group Title DOXIL Trabectedin/DOXIL
    Arm/Group Description 50 mg/m2 DOXIL administered as a 90-minute intravenous (IV) infusion, every 4 weeks 30 mg/m2 DOXIL administered as a 90-minute IV infusion followed by 1.1 mg/m2 trabectedin as a 3-hour IV infusion, every 3 weeks
    Measure Participants 63 93
    Median (95% Confidence Interval) [Months]
    7.7
    7.9
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection DOXIL, Trabectedin/DOXIL
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8203
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio, log
    Estimated Value 0.95
    Confidence Interval (2-Sided) 95%
    0.62 to 1.46
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Median Area Under Curve (AUC) of Trabectedin.
    Description Median simulated area under the curve (AUC) of a 21 day trabectedin profile of participants (of this study) administering trabectedin and doxil, calculated using the trapezoidal rule method. Simulations were based on a dataset created of 1000 participants using the posthoc parameter estimations, derived from the population pharmacokinetic analysis dataset of Trabectedin (Participants=831, with resampling). Plasma concentration-time profiles were simulated up to 504 hour post-dosing using a rich sampling.
    Time Frame Day 1 (Predose; 1.5 hour after start of infusion; 5 minutes, 2 hour and 6 to 20 hour after end of infusion); Day 8 (168 hour after end of infusion); and Day 15 (336 hour after end of infusion) at Cycles 1 and 2

    Outcome Measure Data

    Analysis Population Description
    Blood samples for pharmacokinetic analysis were collected from 86 participants of this study.
    Arm/Group Title Trabectedin/DOXIL
    Arm/Group Description 30 mg/m2 DOXIL administered as a 90-minute IV infusion followed by 1.1 mg/m2 trabectedin as a 3-hour IV infusion, every 3 weeks
    Measure Participants 86
    Number [ng*h/mL]
    74.24
    6. Secondary Outcome
    Title Median Maximum Plasma Concentration (Cmax) of Trabectedin.
    Description Median simulated maximum plasma concentration (Cmax) at 3 hour of a 21 day trabectedin profile of participants (of this study) administering trabectedin and doxil. The assessment of Cmax was based on a dataset created of 1000 participants using the posthoc parameter estimations, derived from the population pharmacokinetic analysis dataset of Trabectedin (participants=831, with resampling). Plasma concentration-time profiles were simulated up to 504 hour post-dosing using a rich sampling.
    Time Frame Day 1 (Predose; 1.5 hour after start of infusion; 5 minutes, 2 hour and 6 to 20 hour after end of infusion); Day 8 (168 hour after end of infusion); and Day 15 (336 hour after end of infusion) at Cycles 1 and 2

    Outcome Measure Data

    Analysis Population Description
    Blood samples for pharmacokinetic analysis were collected from 86 participants of this study.
    Arm/Group Title Trabectedin/DOXIL
    Arm/Group Description 30 mg/m2 DOXIL administered as a 90-minute IV infusion followed by 1.1 mg/m2 trabectedin as a 3-hour IV infusion, every 3 weeks
    Measure Participants 86
    Number [pg/mL]
    13394

    Adverse Events

    Time Frame From the time of the first study-related procedure until up to 30 days after administration of the last dose of study medication.
    Adverse Event Reporting Description Number of treated participants were analyzed for adverse events. 672 participants were randomized (337 in trabectedin + DOXIL arm and 335 in DOXIL arm), out of which 663 participants received treatment ie, 330 participants received DOXIL and 333 received trabectedin + DOXIL and were analyzed for adverse events.
    Arm/Group Title Trabectedin/DOXIL DOXIL
    Arm/Group Description 30 mg/m2 DOXIL administered as a 90-minute IV infusion followed by 1.1 mg/m2 trabectedin as a 3-hour IV infusion, every 3 weeks 50 mg/m2 DOXIL administered as a 90-minute intravenous (IV) infusion, every 4 weeks
    All Cause Mortality
    Trabectedin/DOXIL DOXIL
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Trabectedin/DOXIL DOXIL
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 133/333 (39.9%) 102/330 (30.9%)
    Blood and lymphatic system disorders
    Anaemia 17/333 (5.1%) 7/330 (2.1%)
    Bicytopenia 1/333 (0.3%) 0/330 (0%)
    Bone Marrow Failure 4/333 (1.2%) 1/330 (0.3%)
    Febrile Neutropenia 18/333 (5.4%) 5/330 (1.5%)
    Granulocytopenia 1/333 (0.3%) 0/330 (0%)
    Leukopenia 16/333 (4.8%) 3/330 (0.9%)
    Neutropenia 26/333 (7.8%) 7/330 (2.1%)
    Pancytopenia 6/333 (1.8%) 0/330 (0%)
    Thrombocytopenia 21/333 (6.3%) 1/330 (0.3%)
    Cardiac disorders
    Cardiac Arrest 1/333 (0.3%) 0/330 (0%)
    Cardiac Failure Congestive 2/333 (0.6%) 1/330 (0.3%)
    Electromechanical Dissociation 1/333 (0.3%) 0/330 (0%)
    Palpitations 1/333 (0.3%) 0/330 (0%)
    Ventricular Tachycardia 1/333 (0.3%) 0/330 (0%)
    Congenital, familial and genetic disorders
    Adenomatous Polyposis Coli 1/333 (0.3%) 0/330 (0%)
    Gastrointestinal disorders
    Abdominal Distension 3/333 (0.9%) 1/330 (0.3%)
    Abdominal Pain 6/333 (1.8%) 9/330 (2.7%)
    Aphthous Stomatitis 0/333 (0%) 1/330 (0.3%)
    Ascites 6/333 (1.8%) 7/330 (2.1%)
    Colonic Obstruction 3/333 (0.9%) 2/330 (0.6%)
    Constipation 3/333 (0.9%) 3/330 (0.9%)
    Diarrhoea 6/333 (1.8%) 3/330 (0.9%)
    Enterocutaneous Fistula 1/333 (0.3%) 0/330 (0%)
    Erosive Oesophagitis 0/333 (0%) 1/330 (0.3%)
    Gastrointestinal Disorder 1/333 (0.3%) 0/330 (0%)
    Gastrointestinal Haemorrhage 0/333 (0%) 1/330 (0.3%)
    Gastrointestinal Obstruction 0/333 (0%) 2/330 (0.6%)
    Ileus 1/333 (0.3%) 4/330 (1.2%)
    Intestinal Fistula 1/333 (0.3%) 1/330 (0.3%)
    Intestinal Obstruction 7/333 (2.1%) 11/330 (3.3%)
    Large Intestinal Obstruction 0/333 (0%) 1/330 (0.3%)
    Mechanical Ileus 0/333 (0%) 2/330 (0.6%)
    Mouth Ulceration 0/333 (0%) 2/330 (0.6%)
    Nausea 14/333 (4.2%) 8/330 (2.4%)
    Oesophageal Ulcer 0/333 (0%) 1/330 (0.3%)
    Oesophagitis 0/333 (0%) 2/330 (0.6%)
    Small Intestinal Obstruction 7/333 (2.1%) 3/330 (0.9%)
    Stomatitis 1/333 (0.3%) 2/330 (0.6%)
    Subileus 1/333 (0.3%) 0/330 (0%)
    Upper Gastrointestinal Haemorrhage 1/333 (0.3%) 1/330 (0.3%)
    Vomiting 15/333 (4.5%) 8/330 (2.4%)
    General disorders
    Adverse Drug Reaction 1/333 (0.3%) 1/330 (0.3%)
    Asthenia 0/333 (0%) 2/330 (0.6%)
    Catheter Related Complication 2/333 (0.6%) 0/330 (0%)
    Catheter Site Phlebitis 1/333 (0.3%) 0/330 (0%)
    Chest Discomfort 1/333 (0.3%) 0/330 (0%)
    Chills 1/333 (0.3%) 0/330 (0%)
    Condition Aggravated 1/333 (0.3%) 0/330 (0%)
    Extravasation 1/333 (0.3%) 0/330 (0%)
    Fatigue 8/333 (2.4%) 1/330 (0.3%)
    General Physical Health Deterioration 3/333 (0.9%) 3/330 (0.9%)
    Hernia Obstructive 0/333 (0%) 1/330 (0.3%)
    Hernia Pain 1/333 (0.3%) 0/330 (0%)
    Mucosal Inflammation 0/333 (0%) 3/330 (0.9%)
    Non-Cardiac Chest Pain 2/333 (0.6%) 1/330 (0.3%)
    Oedema Peripheral 3/333 (0.9%) 0/330 (0%)
    Pain 0/333 (0%) 1/330 (0.3%)
    Pyrexia 10/333 (3%) 3/330 (0.9%)
    Sudden Death 0/333 (0%) 1/330 (0.3%)
    Hepatobiliary disorders
    Cholecystitis 0/333 (0%) 1/330 (0.3%)
    Cholelithiasis 1/333 (0.3%) 0/330 (0%)
    Hepatitis 1/333 (0.3%) 0/330 (0%)
    Hepatitis Cholestatic 0/333 (0%) 1/330 (0.3%)
    Hepatitis Toxic 1/333 (0.3%) 0/330 (0%)
    Hyperbilirubinaemia 2/333 (0.6%) 0/330 (0%)
    Immune system disorders
    Anaphylactic Reaction 0/333 (0%) 2/330 (0.6%)
    Drug Hypersensitivity 0/333 (0%) 1/330 (0.3%)
    Hypersensitivity 2/333 (0.6%) 3/330 (0.9%)
    Infections and infestations
    Abscess 1/333 (0.3%) 0/330 (0%)
    Bacteraemia 3/333 (0.9%) 0/330 (0%)
    Bacterial Sepsis 0/333 (0%) 1/330 (0.3%)
    Bronchitis 1/333 (0.3%) 0/330 (0%)
    Catheter Related Infection 3/333 (0.9%) 1/330 (0.3%)
    Catheter Sepsis 1/333 (0.3%) 0/330 (0%)
    Catheter Site Cellulitis 0/333 (0%) 1/330 (0.3%)
    Catheter Site Infection 4/333 (1.2%) 0/330 (0%)
    Cellulitis 1/333 (0.3%) 1/330 (0.3%)
    Central Line Infection 1/333 (0.3%) 0/330 (0%)
    Clostridium Difficile Colitis 1/333 (0.3%) 0/330 (0%)
    Enterocolitis Infectious 0/333 (0%) 1/330 (0.3%)
    Erysipeloid 0/333 (0%) 1/330 (0.3%)
    Helicobacter Gastritis 1/333 (0.3%) 0/330 (0%)
    Herpes Oesophagitis 1/333 (0.3%) 0/330 (0%)
    Infection 1/333 (0.3%) 2/330 (0.6%)
    Influenza 1/333 (0.3%) 0/330 (0%)
    Neutropenic Infection 3/333 (0.9%) 0/330 (0%)
    Neutropenic Sepsis 2/333 (0.6%) 0/330 (0%)
    Oesophageal Candidiasis 0/333 (0%) 1/330 (0.3%)
    Perineal Abscess 1/333 (0.3%) 0/330 (0%)
    Pharyngitis 1/333 (0.3%) 0/330 (0%)
    Pneumonia 3/333 (0.9%) 4/330 (1.2%)
    Pyelonephritis 0/333 (0%) 1/330 (0.3%)
    Respiratory Tract Infection Viral 1/333 (0.3%) 0/330 (0%)
    Sepsis 1/333 (0.3%) 2/330 (0.6%)
    Septic Shock 1/333 (0.3%) 0/330 (0%)
    Staphylococcal Sepsis 1/333 (0.3%) 0/330 (0%)
    Subcutaneous Abscess 0/333 (0%) 1/330 (0.3%)
    Urinary Tract Infection 2/333 (0.6%) 2/330 (0.6%)
    Urinary Tract Infection Bacterial 0/333 (0%) 1/330 (0.3%)
    Urosepsis 0/333 (0%) 1/330 (0.3%)
    Injury, poisoning and procedural complications
    Device Dislocation 0/333 (0%) 1/330 (0.3%)
    Femoral Neck Fracture 0/333 (0%) 1/330 (0.3%)
    Hip Fracture 0/333 (0%) 1/330 (0.3%)
    Medical Device Complication 1/333 (0.3%) 0/330 (0%)
    Postoperative Ileus 1/333 (0.3%) 0/330 (0%)
    Procedural Nausea 0/333 (0%) 1/330 (0.3%)
    Procedural Vomiting 0/333 (0%) 1/330 (0.3%)
    Thoracic Vertebral Fracture 1/333 (0.3%) 0/330 (0%)
    Wound Dehiscence 1/333 (0.3%) 0/330 (0%)
    Investigations
    Alanine Aminotransferase Increased 5/333 (1.5%) 0/330 (0%)
    Aspartate Aminotransferase Increased 5/333 (1.5%) 0/330 (0%)
    Blood Alkaline Phosphatase Increased 3/333 (0.9%) 0/330 (0%)
    Blood Creatine Phosphokinase Increased 1/333 (0.3%) 0/330 (0%)
    Blood Creatinine Increased 1/333 (0.3%) 0/330 (0%)
    Carbohydrate Antigen 125 Increased 1/333 (0.3%) 0/330 (0%)
    Electrocardiogram Change 1/333 (0.3%) 0/330 (0%)
    Gamma-Glutamyltransferase Increased 1/333 (0.3%) 0/330 (0%)
    Hepatic Enzyme Increased 1/333 (0.3%) 0/330 (0%)
    Liver Function Test Abnormal 1/333 (0.3%) 0/330 (0%)
    Transaminases Increased 1/333 (0.3%) 0/330 (0%)
    Metabolism and nutrition disorders
    Anorexia 3/333 (0.9%) 6/330 (1.8%)
    Decreased Appetite 0/333 (0%) 1/330 (0.3%)
    Dehydration 7/333 (2.1%) 4/330 (1.2%)
    Hypoalbuminaemia 0/333 (0%) 1/330 (0.3%)
    Hypokalaemia 1/333 (0.3%) 1/330 (0.3%)
    Hypomagnesaemia 1/333 (0.3%) 0/330 (0%)
    Hyponatraemia 1/333 (0.3%) 1/330 (0.3%)
    Malnutrition 1/333 (0.3%) 0/330 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/333 (0%) 1/330 (0.3%)
    Back Pain 0/333 (0%) 1/330 (0.3%)
    Bone Pain 1/333 (0.3%) 0/330 (0%)
    Rhabdomyolysis 1/333 (0.3%) 0/330 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastases to Central Nervous System 1/333 (0.3%) 0/330 (0%)
    Metastases to Soft Tissue 0/333 (0%) 1/330 (0.3%)
    Oncologic Complication 1/333 (0.3%) 0/330 (0%)
    Paraneoplastic Syndrome 1/333 (0.3%) 0/330 (0%)
    Nervous system disorders
    Cerebrovascular Accident 1/333 (0.3%) 0/330 (0%)
    Convulsion 1/333 (0.3%) 0/330 (0%)
    Dizziness 0/333 (0%) 1/330 (0.3%)
    Grand Mal Convulsion 1/333 (0.3%) 0/330 (0%)
    Headache 0/333 (0%) 1/330 (0.3%)
    Lethargy 0/333 (0%) 2/330 (0.6%)
    Loss of Consciousness 1/333 (0.3%) 0/330 (0%)
    Syncope 2/333 (0.6%) 0/330 (0%)
    Syncope Vasovagal 1/333 (0.3%) 0/330 (0%)
    Psychiatric disorders
    Confusional State 0/333 (0%) 1/330 (0.3%)
    Renal and urinary disorders
    Haematuria 0/333 (0%) 1/330 (0.3%)
    Hydronephrosis 0/333 (0%) 2/330 (0.6%)
    Nephrolithiasis 0/333 (0%) 1/330 (0.3%)
    Obstructive Uropathy 1/333 (0.3%) 0/330 (0%)
    Renal Failure Acute 3/333 (0.9%) 2/330 (0.6%)
    Renal Impairment 1/333 (0.3%) 0/330 (0%)
    Reproductive system and breast disorders
    Oedema Genital 1/333 (0.3%) 0/330 (0%)
    Vaginal Haemorrhage 0/333 (0%) 3/330 (0.9%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 3/333 (0.9%) 3/330 (0.9%)
    Hydrothorax 1/333 (0.3%) 0/330 (0%)
    Hypoxia 1/333 (0.3%) 0/330 (0%)
    Pleural Effusion 3/333 (0.9%) 3/330 (0.9%)
    Pulmonary Embolism 13/333 (3.9%) 6/330 (1.8%)
    Respiratory Failure 1/333 (0.3%) 0/330 (0%)
    Skin and subcutaneous tissue disorders
    Erythema 0/333 (0%) 1/330 (0.3%)
    Melanosis 1/333 (0.3%) 0/330 (0%)
    Palmar-Plantar Erythrodysaesthesia Syndrome 0/333 (0%) 4/330 (1.2%)
    Pruritus 1/333 (0.3%) 0/330 (0%)
    Rash 1/333 (0.3%) 0/330 (0%)
    Urticaria 1/333 (0.3%) 0/330 (0%)
    Vascular disorders
    Arterial Insufficiency 1/333 (0.3%) 0/330 (0%)
    Axillary Vein Thrombosis 2/333 (0.6%) 0/330 (0%)
    Deep Vein Thrombosis 1/333 (0.3%) 2/330 (0.6%)
    Haemorrhage 1/333 (0.3%) 0/330 (0%)
    Hypotension 1/333 (0.3%) 0/330 (0%)
    Jugular Vein Thrombosis 1/333 (0.3%) 0/330 (0%)
    Peripheral Ischaemia 1/333 (0.3%) 0/330 (0%)
    Subclavian Vein Thrombosis 2/333 (0.6%) 0/330 (0%)
    Thrombosis 3/333 (0.9%) 0/330 (0%)
    Vena Cava Thrombosis 0/333 (0%) 1/330 (0.3%)
    Venous Occlusion 1/333 (0.3%) 0/330 (0%)
    Other (Not Including Serious) Adverse Events
    Trabectedin/DOXIL DOXIL
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 333/333 (100%) 318/330 (96.4%)
    Blood and lymphatic system disorders
    Anaemia 160/333 (48%) 82/330 (24.8%)
    Leukopenia 164/333 (49.2%) 91/330 (27.6%)
    Neutropenia 256/333 (76.9%) 128/330 (38.8%)
    Thrombocytopenia 115/333 (34.5%) 27/330 (8.2%)
    Gastrointestinal disorders
    Abdominal Distension 18/333 (5.4%) 23/330 (7%)
    Abdominal Pain 70/333 (21%) 76/330 (23%)
    Abdominal Pain Upper 19/333 (5.7%) 25/330 (7.6%)
    Ascites 13/333 (3.9%) 18/330 (5.5%)
    Constipation 109/333 (32.7%) 92/330 (27.9%)
    Diarrhoea 84/333 (25.2%) 63/330 (19.1%)
    Dyspepsia 43/333 (12.9%) 35/330 (10.6%)
    Mouth Ulceration 11/333 (3.3%) 21/330 (6.4%)
    Nausea 251/333 (75.4%) 139/330 (42.1%)
    Stomatitis 67/333 (20.1%) 108/330 (32.7%)
    Vomiting 188/333 (56.5%) 97/330 (29.4%)
    General disorders
    Asthenia 56/333 (16.8%) 38/330 (11.5%)
    Fatigue 153/333 (45.9%) 122/330 (37%)
    Mucosal Inflammation 42/333 (12.6%) 64/330 (19.4%)
    Oedema Peripheral 30/333 (9%) 28/330 (8.5%)
    Pain 18/333 (5.4%) 12/330 (3.6%)
    Pyrexia 63/333 (18.9%) 44/330 (13.3%)
    Hepatobiliary disorders
    Hyperbilirubinaemia 51/333 (15.3%) 25/330 (7.6%)
    Infections and infestations
    Urinary Tract Infection 15/333 (4.5%) 19/330 (5.8%)
    Investigations
    Alanine Aminotransferase Increased 185/333 (55.6%) 33/330 (10%)
    Aspartate Aminotransferase Increased 139/333 (41.7%) 35/330 (10.6%)
    Blood Alkaline Phosphatase Increased 77/333 (23.1%) 29/330 (8.8%)
    Blood Creatine Phosphokinase Increased 23/333 (6.9%) 11/330 (3.3%)
    Blood Creatinine Increased 21/333 (6.3%) 20/330 (6.1%)
    Metabolism and nutrition disorders
    Anorexia 109/333 (32.7%) 85/330 (25.8%)
    Hypoalbuminaemia 22/333 (6.6%) 19/330 (5.8%)
    Hypokalaemia 38/333 (11.4%) 26/330 (7.9%)
    Hyponatraemia 19/333 (5.7%) 11/330 (3.3%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 21/333 (6.3%) 14/330 (4.2%)
    Back Pain 30/333 (9%) 31/330 (9.4%)
    Myalgia 18/333 (5.4%) 12/330 (3.6%)
    Pain in Extremity 20/333 (6%) 18/330 (5.5%)
    Nervous system disorders
    Dizziness 33/333 (9.9%) 22/330 (6.7%)
    Dysgeusia 19/333 (5.7%) 10/330 (3%)
    Headache 55/333 (16.5%) 24/330 (7.3%)
    Psychiatric disorders
    Anxiety 23/333 (6.9%) 11/330 (3.3%)
    Insomnia 34/333 (10.2%) 16/330 (4.8%)
    Respiratory, thoracic and mediastinal disorders
    Cough 41/333 (12.3%) 40/330 (12.1%)
    Dyspnoea 52/333 (15.6%) 33/330 (10%)
    Pharyngolaryngeal Pain 17/333 (5.1%) 24/330 (7.3%)
    Skin and subcutaneous tissue disorders
    Alopecia 42/333 (12.6%) 48/330 (14.5%)
    Dry Skin 18/333 (5.4%) 10/330 (3%)
    Erythema 18/333 (5.4%) 19/330 (5.8%)
    Palmar-Plantar Erythrodysaesthesia Syndrome 86/333 (25.8%) 179/330 (54.2%)
    Pruritus 11/333 (3.3%) 20/330 (6.1%)
    Rash 36/333 (10.8%) 59/330 (17.9%)
    Skin Hyperpigmentation 21/333 (6.3%) 24/330 (7.3%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Director Clinical Research Medical Leader
    Organization Janssen R&D US
    Phone 908 704 5779
    Email
    Responsible Party:
    Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
    ClinicalTrials.gov Identifier:
    NCT00113607
    Other Study ID Numbers:
    • CR003448
    • ET743-OVA-301
    • 2004-005276-16
    First Posted:
    Jun 10, 2005
    Last Update Posted:
    Jun 27, 2014
    Last Verified:
    Jun 1, 2014