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

This study has been completed.
Sponsor:
Collaborator:
PharmaMar
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00113607
First received: June 9, 2005
Last updated: December 13, 2013
Last verified: December 2013
  Purpose

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 Intervention Phase
Ovarian Cancer
Drug: Trabectedin
Drug: DOXIL
Drug: Dexamethasone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    PFS is defined as the time between randomization and disease progression or death.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: From the date of randomization until the date of death, as assessed for approximately 3 years ] [ Designated as safety issue: Yes ]
    Overall survival was defined as the time between the randomization and death

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 672
Study Start Date: April 2005
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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.
Other Name: Dexamethasone
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 Name: CAELYX

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00113607

  Show 112 Study Locations
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.
  More Information

Additional Information:
No publications provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier: NCT00113607     History of Changes
Other Study ID Numbers: CR003448, ET743-OVA-301, 2004-005276-16
Study First Received: June 9, 2005
Results First Received: June 18, 2013
Last Updated: December 13, 2013
Health Authority: United States: Food and Drug Administration

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
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Trabectedin
Doxorubicin
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on April 23, 2014