A Study to Assess the Potential Effects of a Single-Dose Administration of Trabectedin on the QT Intervals of the Electrocardiogram

This study has been completed.
Sponsor:
Collaborator:
PharmaMar
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00786838
First received: November 4, 2008
Last updated: March 13, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to assess the potential effects of trabectedin on the QT/QTc interval duration measured by electrocardiograms (ECGs) in participants with advanced solid tumor malignancies when administered at a therapeutic dose.


Condition Intervention Phase
Solid Tumor
Drug: Trabectedin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: A Single-Blind, Multicenter, Placebo-Controlled, Sequential Design Study Evaluating the Potential Effects of a Single-Dose Administration of Trabectedin on the QT Intervals of the Electrocardiogram

Resource links provided by NLM:


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

Primary Outcome Measures:
  • The Difference in the Change From Baseline (Predose on Day 1) in QTc Intervals Trabectedin Relative to Placebo at 24 Hour Post Dose by Fridericia Correction [ Time Frame: Baseline (predose on Day 1) to 24 hour post dose (Day 1 or Day 2) ] [ Designated as safety issue: No ]
    QTc interval was measured by electrocardiograms to evaluate the potential effect of trabectedin on QTc interval duration. The Fridericia correction was used as the standard clinical correction for calculating the heart rate-corrected QT interval.

  • The Difference in the Change From Baseline (Predose on Day 1) in QTc Intervals Trabectedin Relative to Placebo at 24 Hour Post Dose by Bazett's Correction [ Time Frame: Baseline (predose on Day 1) to 24 hour post dose (Day 1 or Day 2) ] [ Designated as safety issue: No ]
    QTc interval was measured by electrocardiograms to evaluate the potential effect of trabectedin on QTc interval duration. The Bazett's Correction was used as the standard clinical correction for calculating the heart rate-corrected QT interval.


Secondary Outcome Measures:
  • Maximum Plasma Concentration of Trabectedin (Cmax) [ Time Frame: Baseline (predose on Day 2) to 24 hour post dose (Day 2 or Day 3). ] [ Designated as safety issue: No ]
  • Time Taken to Acheive Maximum Plasma Concentration (Tmax) [ Time Frame: Baseline (predose on Day 2) to 24 hour post dose (Day 2 or Day 3). ] [ Designated as safety issue: No ]
  • Number of Participants With QTc Interval Increase From Baseline (Predose on Day 1) Greater Than 30 Milli Seconds [ Time Frame: Baseline (predose) to approximately 24 hour post dose ] [ Designated as safety issue: No ]
    The Fridericia (QTcF) and Bazett's (QTcB) correction were used as the standard clinical correction for calculating the heart rate-corrected QT interval.

  • Number of Participants With QTc Interval Increase From Baseline (Predose on Day 1) Greater Than 60 Milli Seconds [ Time Frame: Baseline (predose) to approximately 24 hour post dose ] [ Designated as safety issue: No ]
    The Fridericia (QTcF) and Bazett's (QTcB) correction were used as the standard clinical correction for calculating the heart rate-corrected QT interval.

  • Number of Participants With QTc Interval Greater Than 450 Milli Seconds [ Time Frame: Baseline (predose) to approximately 24 hour post dose ] [ Designated as safety issue: No ]
    The Fridericia (QTcF) and Bazett's (QTcB) correction were used as the standard clinical correction for calculating the heart rate-corrected QT interval.

  • Number of Participants With QTc Interval Greater Than 480 Milli Seconds [ Time Frame: Baseline (predose) to approximately 24 hour post dose ] [ Designated as safety issue: No ]
    The Fridericia (QTcF) and Bazett's (QTcB) correction were used as the standard clinical correction for calculating the heart rate-corrected QTc interval.

  • Number of Participants With QTc Interval Greater Than 500 Milli Seconds [ Time Frame: Baseline (predose) to approximately 24 hour post dose ] [ Designated as safety issue: No ]
    The Fridericia (QTcF) and Bazett's (QTcB) correction were used as the standard clinical correction for calculating the heart rate-corrected QTc interval.

  • Number of Participants With PR Interval Greater Than 200 Milli Seconds [ Time Frame: Baseline (predose) to approximately 24 hour post dose ] [ Designated as safety issue: No ]
    PR interval is the portion of the electrocardiogram between the onset of the P wave (atrial depolarization) and the QRS complex (ventricular depolarization).

  • Number of Participants With QRS Interval Greater Than 120 Milli Seconds [ Time Frame: Baseline (predose) to approximately 24 hour post dose ] [ Designated as safety issue: No ]
    QRS interval is the interval from the beginning of the Q wave to the termination of the S wave, representing the time for ventricular depolarization.

  • Mean Heart Rate (Beats Per Minute) Over 24 Hours Postdose [ Time Frame: Baseline (predose on Day 1) to 24 hour post dose ] [ Designated as safety issue: No ]

Enrollment: 76
Study Start Date: October 2008
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Trabectedin
3-hour placebo intravenous infusion on Day 1 and trabectedin 1.3 mg/m2 3-hour intravenous infusion on Day 2 (single-blind). Patients may continue treatment with trabectedin until clinical benefit or drug is commercially available (open-label).
Drug: Trabectedin
Trabectedin will be administered as 1.3 mg/m2 3-hour intravenous infusion on Day 2.
Drug: Placebo
Participants will receive 3-hour placebo intravenous infusion on Day 1.

Detailed Description:

This is a single-blind (where the participant does not know the treatment he receives), multicenter (study conducted at multiple sites), placebo-controlled (an inactive substance that is compared with the study medication to test whether the study medication has a real effect in clinical study), sequential design (it is a design in a single group of Participants where one or more study medication is administered in a sequence) study to evaluate the potential effects of a single-dose administration of trabectedin on the QT intervals of the electrocardiogram (ECG). Initially, the study will consist of 2 phases: a screening phase (within 21 days before administration of the study medication), and a single-blind treatment phase (for 2 days). Participants who complete the single-blind treatment phase will be opted to take trabectedin in an open-label extension (for a minimum of 6 cycles), as long as they derive a clinical benefit (ie, until there is clear evidence of disease progression or unacceptable toxicity, as judged by the investigator). Participants will be assessed for ECG on predose before the single-blind treatment phase. During the single-blind treatment phase, a placebo control will be given on Day 1, and trabectedin (1.3 mg per square meter) will be administered on Day 2. Participants will be monitored until completion of the 24 hour pharmacokinetic blood sample collection. During the open-label extension (21 days after completion of the single-blind treatment phase), all Participants will receive trabectedin intravenously on Day 1 of each 17- to 49 day treatment cycle. The dose and schedule of trabectedin will be modified according to the type of malignancy being treated (ie, sarcoma, ovarian, or breast cancer). Safety evaluations will include assessment of adverse events, vital signs, physical examination, and clinical laboratory tests which will be performed throughout the study. The study duration for the open-label extension will vary by participant.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants with locally advanced or metastatic solid tumors who have received three or less prior lines of systemic chemotherapy
  • Participants must have relapsed or had progressive disease following standard of care treatment with chemotherapy prior to enrollment, or intolerant to prior standard of care treatment with chemotherapy
  • Normal cardiac conduction and function as documented on a 12-lead electrocardiogram
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
  • Adequate organ function as evidenced by laboratory tests
  • Able to receive dexamethasone or its equivalent
  • Agrees to protocol-defined use of effective contraception

Exclusion Criteria:

  • Participants treated with more than three prior chemotherapy regimens (including adjuvant therapy)
  • Previous exposure to trabectedin
  • Central nervous system (CNS) metastasis
  • Known hypersensitivity to any of the components of the trabectedin intravenous formulation or dexamethasone
  • Heart rhythm disturbances, unusual T wave and U wave (if present) morphology, blood pressure outside of normal range, a history of cardiac failure, myocardial infarction, or cardiomyopathy, or a history of additional risk factors for torsade de pointes (eg, heart failure, electrolyte abnormalities, family history of Long QT Syndrome)
  • Participants who at screening are on medication that is known to prolong the QT interval or who is on CYP3A4 inhibitors or inducers
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00786838

Locations
United States, Florida
Miami, Florida, United States
United States, North Carolina
Charlotte, North Carolina, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
United States, Washington
Tacoma, Washington, United States
Belgium
Brussels, Belgium
Edegem, Belgium
Wilrijk, Belgium
France
Lyon, France
Marseille, France
Montpellier, France
Villejuif, France
India
Bangalore N/A, India
Pune, India
Korea, Republic of
Seoul, Korea, Republic of
Russian Federation
Moscow, Russian Federation
Moscow N/A, Russian Federation
St Petersburg N/A, Russian Federation
St-Petersburg, Russian Federation
Spain
Sanchinarro, Spain
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: NCT00786838     History of Changes
Other Study ID Numbers: CR014917, ET743OVC1001
Study First Received: November 4, 2008
Results First Received: March 29, 2013
Last Updated: March 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Solid tumor
Advanced solid tumor
Malignant tumors
Sarcoma
Breast tumor
Ovarian tumor
QT interval
Trabectedin
Yondelis
Ecteinascidin 743
ET743

Additional relevant MeSH terms:
Trabectedin
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 24, 2014