Solid TumorPhase 2NCT00786838
A Study to Assess the Potential Effects of a Single-Dose Administration of Trabectedin on the QT Intervals of the Electrocardiogram
A Phase 2 study testing Trabectedin in people with Solid Tumor, run by Johnson & Johnson Pharmaceutical Research & Development, L.L.C. at 17 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Solid Tumor
- What is being tested?
- Trabectedin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 76 participants
- Where
- 17 sitesin 7 countries
- Study dates
- Oct 2008to Dec 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
17 sites in 7 countries.
17 sites in 7 countries
United States4 sites
Study site
Charlotte, North Carolina
Study site
Miami, Florida
Study site
Philadelphia, Pennsylvania
Study site
Tacoma, Washington
France4 sites
Study site
Lyon
Study site
Marseille
Study site
Montpellier
Study site
Villejuif
About this study
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
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.
Read the 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.
- Conditions
- Solid Tumor
- Being tested
- Trabectedin, Placebo
- Keywords
- Solid tumor, Advanced solid tumor, Malignant tumors, Sarcoma, Breast tumor, Ovarian tumor, QT interval, Trabectedin, Yondelis, Ecteinascidin 743, ET743
- Medical subject headings
- Neoplasms, Sarcoma, Breast Neoplasms, Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| Trabectedin | Experimental | 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). Receives: Drug: Trabectedin; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline (predose on Day 1) to 24 hour post dose (Day 1 or Day 2)
Secondary outcomes (10)
Maximum Plasma Concentration of Trabectedin (Cmax)
Measured: Baseline (predose on Day 2) to 24 hour post dose (Day 2 or Day 3).
Time Taken to Acheive Maximum Plasma Concentration (Tmax)
Measured: 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.
Measured: 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
The Fridericia (QTcF) and Bazett's (QTcB) correction were used as the standard clinical correction for calculating the heart rate-corrected QT interval.
Measured: Baseline (predose) to approximately 24 hour post dose
Number of Participants With QTc Interval Greater Than 450 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.
Measured: Baseline (predose) to approximately 24 hour post dose
Number of Participants With QTc Interval Greater Than 480 Milli Seconds
The Fridericia (QTcF) and Bazett's (QTcB) correction were used as the standard clinical correction for calculating the heart rate-corrected QTc interval.
Measured: Baseline (predose) to approximately 24 hour post dose
Number of Participants With QTc Interval Greater Than 500 Milli Seconds
The Fridericia (QTcF) and Bazett's (QTcB) correction were used as the standard clinical correction for calculating the heart rate-corrected QTc interval.
Measured: Baseline (predose) to approximately 24 hour post dose
Number of Participants With PR Interval Greater Than 200 Milli Seconds
PR interval is the portion of the electrocardiogram between the onset of the P wave (atrial depolarization) and the QRS complex (ventricular depolarization).
Measured: Baseline (predose) to approximately 24 hour post dose
Number of Participants With QRS Interval Greater Than 120 Milli Seconds
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.
Measured: Baseline (predose) to approximately 24 hour post dose
Mean Heart Rate (Beats Per Minute) Over 24 Hours Postdose
Measured: Baseline (predose on Day 1) to 24 hour post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2008 (estimated)
- Study startOct 2008
- Primary completionDec 2009
- Study completionDec 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PharmaMar
- Responsible party
- Sponsor
- Investigators
- Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial, Study director, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00786838
- Sponsor's protocol ID
- CR014917
- Other IDs
- ET743OVC1001
- Status last verified
- Mar 2014
- First submitted
- 4 Nov 2008
- Last updated
- 11 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 21739119
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00786838
- Acronym / sponsor ID
- CR014917
- Conditions
- Solid Tumor
- Keywords
- Solid tumor, Advanced solid tumor, Malignant tumors, Sarcoma, Breast tumor, Ovarian tumor, QT interval, Trabectedin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Johnson & Johnson Pharmaceutical Research & Development, L.L.C.Industry (pharma, biotech, devices)
- Collaborators
- PharmaMar
- Study start
- Oct 2008
- Primary completion
- Dec 2009 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 6 Nov 2008 (estimated)
- Results
- Posted 23 Jan 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Single blind (participant)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Trabectedin | Experimental | Drug: Trabectedin, Drug: Placebo3-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). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (6 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TrabectedinTrabectedin will be administered as 1.3 mg/m2 3-hour intravenous infusion on Day 2. | Drug | Trabectedin |
| PlaceboParticipants will receive 3-hour placebo intravenous infusion on Day 1. | Drug | Trabectedin |
Primary outcome
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)
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)
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.
10 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
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
Time frame: Baseline (predose) to approximately 24 hour post dose
Number of Participants With QTc Interval Greater Than 450 Milli Seconds
Time frame: Baseline (predose) to approximately 24 hour post dose
Number of Participants With QTc Interval Greater Than 480 Milli Seconds
Time frame: Baseline (predose) to approximately 24 hour post dose
Number of Participants With QTc Interval Greater Than 500 Milli Seconds
Time frame: Baseline (predose) to approximately 24 hour post dose
Number of Participants With PR Interval Greater Than 200 Milli Seconds
Time frame: Baseline (predose) to approximately 24 hour post dose
Number of Participants With QRS Interval Greater Than 120 Milli Seconds
Time frame: Baseline (predose) to approximately 24 hour post dose
Mean Heart Rate (Beats Per Minute) Over 24 Hours Postdose
Time frame: Baseline (predose on Day 1) to 24 hour post dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 21739119Thertulien 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.
- A Placebo-Controlled Study Evaluating the Potential Effects of Trabectedin on the Heart in Patients with Advanced CancerLink provided by the sponsor.
Related trials for Solid Tumor
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial study director
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
17 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Trabectedin in people with Solid Tumor, run by Johnson & Johnson Pharmaceutical Research & Development, L.L.C. at 17 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, France, Belgium, India, Russia and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: Baseline (predose on Day 1) to 24 hour post dose (Day 1 or Day 2)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00786838, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2014.