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

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.76 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Solid Tumor

Interventions

TrabectedinDRUG

Trabectedin will be administered as 1.3 mg/m2 3-hour intravenous infusion on Day 2.

PlaceboDRUG

Participants will receive 3-hour placebo intravenous infusion on Day 1.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (17)

Unnamed facility

Miami, Florida, United States

Unnamed facility

Charlotte, North Carolina, United States

Unnamed facility

Philadelphia, Pennsylvania, United States

Outcomes

Primary Outcomes

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

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.

Time frame: Baseline (predose on Day 1) to 24 hour post dose (Day 1 or Day 2)

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

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.

Time frame: Baseline (predose on Day 1) to 24 hour post dose (Day 1 or Day 2)

Secondary Outcomes

Maximum Plasma Concentration of Trabectedin (Cmax)

Time frame: Baseline (predose on Day 2) to 24 hour post dose (Day 2 or Day 3).

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).

Number of Participants With QTc Interval Increase From Baseline (Predose on Day 1) Greater Than 30 Milli Seconds

The Fridericia (QTcF) and Bazett's (QTcB) correction were used as the standard clinical correction for calculating the heart rate-corrected QT interval.

Time frame: Baseline (predose) to approximately 24 hour post dose

Number of Participants With QTc Interval Increase From Baseline (Predose on Day 1) Greater Than 60 Milli Seconds

Data from ClinicalTrials.gov

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