Clinical trial NCT00786838: A Study to Assess the Potential Effects of a Single-Dose Administration of Trabectedin on the QT Intervals of the Electrocardiogram
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Solid Tumor
Keywords: Solid tumor
Advanced solid tumor
Malignant tumors
Sarcoma
Breast tumor
Ovarian tumor
QT interval
Trabectedin
Yondelis
Ecteinascidin 743
ET743
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
Collaborators: name: PharmaMar
First posted: 2008-11-06
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: 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
timeFrame: Baseline (predose on Day 1) to 24 hour post dose (Day 1 or Day 2)
measure: 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
timeFrame: Baseline (predose on Day 1) to 24 hour post dose (Day 1 or Day 2)
Secondary outcomes:
measure: Maximum Plasma Concentration of Trabectedin (Cmax)
timeFrame: Baseline (predose on Day 2) to 24 hour post dose (Day 2 or Day 3).
measure: Time Taken to Acheive Maximum Plasma Concentration (Tmax)
timeFrame: Baseline (predose on Day 2) to 24 hour post dose (Day 2 or Day 3).
measure: Number of Participants With QTc Interval Increase From Baseline (Predose on Day 1) Greater Than 30 Milli Seconds
timeFrame: Baseline (predose) to approximately 24 hour post dose
measure: Number of Participants With QTc Interval Increase From Baseline (Predose on Day 1) Greater Than 60 Milli Seconds
timeFrame: Baseline (predose) to approximately 24 hour post dose
measure: Number of Participants With QTc Interval Greater Than 450 Milli Seconds
timeFrame: Baseline (predose) to approximately 24 hour post dose
measure: Number of Participants With QTc Interval Greater Than 480 Milli Seconds
timeFrame: Baseline (predose) to approximately 24 hour post dose
measure: Number of Participants With QTc Interval Greater Than 500 Milli Seconds
timeFrame: Baseline (predose) to approximately 24 hour post dose
measure: Number of Participants With PR Interval Greater Than 200 Milli Seconds
timeFrame: Baseline (predose) to approximately 24 hour post dose
measure: Number of Participants With QRS Interval Greater Than 120 Milli Seconds
timeFrame: Baseline (predose) to approximately 24 hour post dose
measure: Mean Heart Rate (Beats Per Minute) Over 24 Hours Postdose
timeFrame: Baseline (predose on Day 1) to 24 hour post dose
Other outcomes:
Locations:
city: Miami
country: United States
state: Florida
city: Charlotte
country: United States
state: North Carolina
city: Philadelphia
country: United States
state: Pennsylvania
city: Tacoma
country: United States
state: Washington
city: Brussels
country: Belgium
city: Edegem
country: Belgium
city: Wilrijk
country: Belgium
city: Lyon
country: France
city: Marseille
country: France
city: Montpellier
country: France
city: Villejuif
country: France
city: Bangalore N/A
country: India
city: Pune
country: India
city: Seoul
country: Korea, Republic of
city: Moscow N/A
country: Russian Federation
city: Moscow
country: Russian Federation
city: St Petersburg N/A
country: Russian Federation
city: St-Petersburg
country: Russian Federation
city: Sanchinarro
country: Spain
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Thertulien R, Manikhas GM, Dirix LY, Vermorken JB, Park K, Jain MM, Jiao JJ, Natarajan J, Parekh T, Zannikos P, Staddon AP. Effect of trabectedin on the QT interval in patients with advanced solid tumor malignancies. Cancer Chemother Pharmacol. 2012 Feb;69(2):341-50. doi: 10.1007/s00280-011-1697-6. Epub 2011 Jul 8.