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

June 18, 2014 updated by: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

672

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina
      • Mendoza, Argentina
      • Sante Fe, Argentina
  • Australia
      • Adelaide, Australia
      • Bentleigh, Australia
      • Douglas, Australia
      • St Leonards, Australia
      • Toorak Gardens, Australia
  • Belgium
      • Edegem, Belgium
      • Hasselt, Belgium
      • Leuven, Belgium
      • Wilrijk, Belgium
  • Brazil
      • Barretos, Brazil
      • Belo Horizonte, Brazil
      • Cerqueira Cesar, Brazil
      • Londrina, Brazil
      • Santo Andre, Brazil
      • Sao Paulo, Brazil
  • Canada
    • Alberta
      • Calgary, Alberta, Canada
      • Edmonton, Alberta, Canada
    • Ontario
      • Ottawa, Ontario, Canada
    • Quebec
      • Montreal, Quebec, Canada
      • Quebec City, Quebec, Canada
  • Chile
      • Reneca, Chile
      • Santiago, Chile
  • China
      • Beijing, China
      • Guangzhou, China
      • Hangzhou, China
      • Jinan, China
      • Shanghai, China
  • France
      • Chartres, France
      • Paris, France
      • Pierre Benite Cedex, France
  • Germany
      • Düsseldorf, Germany
      • Heidelberg, Germany
      • Jena, Germany
      • Karlsruhe, Germany
      • Mainz, Germany
      • Villingen-Schwenningen, Germany
      • Wilhelmshaven, Germany
  • Hong Kong
      • Chai Wan, Hong Kong
      • Hong Kong, Hong Kong
      • Sha Tin, Hong Kong
  • Korea, Republic of
      • Seoul, Korea, Republic of
  • Netherlands
      • Amsterdam, Netherlands
      • Enschede, Netherlands
      • Groningen, Netherlands
      • Maastricht, Netherlands
  • Poland
      • Gdansku, Poland
      • Gliwice, Poland
      • Krakow, Poland
      • Olsztyn, Poland
      • Poznan, Poland
      • Warszawa Poland, Poland
      • Wroclaw, Poland
  • Russian Federation
      • Chelyabinsk, Russian Federation
      • Moscow, Russian Federation
      • Moscow N/A, Russian Federation
      • Obninsk, Kaluga Region, Russian Federation
      • Orenburg, Russian Federation
      • Saint Petersburg, Russian Federation
      • Samara, Russian Federation
      • St. Petersburg, Russian Federation
  • Singapore
      • Singapore, Singapore
  • Spain
      • Barcelona, Spain
      • Girona, Spain
      • Guadalajara, Spain
      • L'Hospitalet De Llobregat, Spain
      • Madrid, Spain
      • Maranon, Spain
      • Valencia, Spain
      • Zaragoza, Spain
  • Sweden
      • Göteborg, Sweden
      • Umeå, Sweden
      • Uppsala, Sweden
  • Taiwan
      • Kaohsiung County, Taiwan
      • Taipei, Taiwan
      • Tao-Yuan, Taiwan
  • United Kingdom
      • Birmingham, United Kingdom
      • Edinburgh, United Kingdom
      • Leicester, United Kingdom
      • London, United Kingdom
      • Nottingham, United Kingdom
      • Poole, United Kingdom
      • Sheffield, United Kingdom
  • United States
    • Alabama
      • Mobile, Alabama, United States
    • Arizona
      • Tucson, Arizona, United States
    • California
      • Los Angeles, California, United States
      • Newport Beach, California, United States
      • Orange, California, United States
    • Colorado
      • Englewood, Colorado, United States
    • Connecticut
      • Stamford, Connecticut, United States
    • Florida
      • Tampa, Florida, United States
    • Idaho
      • Coeur D Alene, Idaho, United States
    • Kentucky
      • Louisville, Kentucky, United States
    • Louisiana
      • New Orleans, Louisiana, United States
    • Massachusetts
      • Boston, Massachusetts, United States
    • Minnesota
      • Minneapolis, Minnesota, United States
    • Missouri
      • Saint Louis, Missouri, United States
    • New Jersey
      • Morristown, New Jersey, United States
    • New York
      • New York, New York, United States
    • North Carolina
      • Charlotte, North Carolina, United States
      • Greenville, North Carolina, United States
      • Winston Salem, North Carolina, United States
    • Ohio
      • Cleveland, Ohio, United States
      • Toledo, Ohio, United States
    • Oregon
      • Portland, Oregon, United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States
    • South Carolina
      • Greenville, South Carolina, United States
    • Tennessee
      • Chattanooga, Tennessee, United States
      • Nashville, Tennessee, United States
    • Texas
      • Dallas, Texas, United States
      • Galveston, Texas, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS): Independent Radiologist Review
Time Frame: 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.
From the date of randomization until the date of disease progression or death, as assessed for approximately 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: 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
From the date of randomization until the date of death, as assessed for approximately 3 years
Objective Response Rate (ORR) - Independent Radiologist Review
Time Frame: 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.
From the date of randomization until the date of disease progression or death, as assessed for approximately 3 years
Duration of Response: Independent Radiologist Review
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
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.
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
Median Area Under Curve (AUC) of Trabectedin.
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
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.
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 Maximum Plasma Concentration (Cmax) of Trabectedin.
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
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.
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Collaborators

PharmaMar

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2005

Primary Completion (Actual)

November 1, 2010

Study Completion (Actual)

November 1, 2010

Study Registration Dates

First Submitted

June 9, 2005

First Submitted That Met QC Criteria

June 9, 2005

First Posted (Estimate)

June 10, 2005

Study Record Updates

Last Update Posted (Estimate)

June 27, 2014

Last Update Submitted That Met QC Criteria

June 18, 2014

Last Verified

June 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR003448
  • ET743-OVA-301 (Other Identifier: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.)
  • 2004-005276-16 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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