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

NCT00786838 | Completed Phase 2 Results

• 2 other identifiers: CR014917ET743OVC1001
• Study Type: interventional
• Target: 76
• Locations: 7 countries
• Sites: 17

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.

Conditions

Solid Tumor

Keywords

Solid tumor; Advanced solid tumor; Malignant tumors; Sarcoma; Breast tumor; Ovarian tumor; QT interval; Trabectedin; Yondelis; Ecteinascidin 743; ET743

Outcome Measures

Primary Outcomes (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 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.

  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.

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

Secondary Outcomes (10)

• Maximum Plasma Concentration of Trabectedin (Cmax)

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

• Time Taken to Acheive Maximum Plasma Concentration (Tmax)

  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

  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

  Baseline (predose) to approximately 24 hour post dose

• Number of Participants With QTc Interval Greater Than 450 Milli Seconds

  Baseline (predose) to approximately 24 hour post dose

Study Arms (1)

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).

Drug: Trabectedin; Drug: Placebo

Interventions

Trabectedin DRUG

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

Trabectedin

Placebo DRUG

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

Trabectedin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.: lead
• PharmaMar: collaborator

Study Sites (17)

Unknown Facility

Miami, Florida, United States

Location

Unknown Facility

Charlotte, North Carolina, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, United States

Location

Unknown Facility

Tacoma, Washington, United States

Location

Unknown Facility

Brussels, Belgium

Location

Unknown Facility

Edegem, Belgium

Location

Unknown Facility

Wilrijk, Belgium

Location

Unknown Facility

Lyon, France

Location

Unknown Facility

Marseille, France

Location

Unknown Facility

Montpellier, France

Location

Unknown Facility

Villejuif, France

Location

Unknown Facility

Bengaluru, India

Location

Unknown Facility

Pune, India

Location

Unknown Facility

Moscow, Russia

Location

Unknown Facility

Saint Petersburg, Russia

Location

Unknown Facility

Seoul, South Korea

Location

Unknown Facility

PAU de Sanchinarro, Spain

Location

Related Publications (1)

• 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.

  PMID: 21739119 DERIVED

Related Links

• A Placebo-Controlled Study Evaluating the Potential Effects of Trabectedin on the Heart in Patients with Advanced Cancer

MeSH Terms

Conditions

Neoplasms; Sarcoma; Breast Neoplasms; Ovarian Neoplasms

Interventions

Trabectedin

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Senior Medical Director
• Organization: Johnson & Johnson Pharmaceutical Research and Development, L.L.C.

1 908 704-5779

Study Officials

• Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial

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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2008
• First Posted: November 6, 2008
• Study Start: October 1, 2008
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: April 11, 2014
• Results First Posted: January 23, 2014

Record last verified: 2014-03

Locations

FR (4); BE (3); IN (2); RU (2); KR (1); US (4); ES (1)