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A Study to Assess the Potential Effects of Ketoconazole on the Pharmacokinetics of Trabectedin in Patients With Advanced Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01267084
Recruitment Status : Completed
First Posted : December 24, 2010
Last Update Posted : October 14, 2015
Sponsor:
Collaborator:
PharmaMar
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE December 23, 2010
First Posted Date  ICMJE December 24, 2010
Last Update Posted Date October 14, 2015
Study Start Date  ICMJE February 2011
Actual Primary Completion Date November 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 13, 2014)
  • Pharmacokinetics of trabectedin [ Time Frame: At protocol-specified time points for up to 8 days during each 21-day cycle in Sequence 1 and Sequence 2 ]
  • Pharmacokinetics of ketoconazole [ Time Frame: 1 day during Sequence 1 or Sequence 2 after ketoconazole is coadministered with trabectedin ]
    This will be measured when ketoconazole will be administered.
Original Primary Outcome Measures  ICMJE
 (submitted: December 23, 2010)
  • Pharmacokinetics of trabectedin [ Time Frame: At protocol-specified time points for up to 8 days during each 21-day cycle in Sequence 1 and Sequence 2 ]
  • Pharmacokinetics of ketoconazole [ Time Frame: 1 day during Sequence 1 and Sequence 2 after ketoconazole is coadministered with trabectedin ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 23, 2010)
  • Number of patients with adverse events [ Time Frame: Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin ]
  • Findings from clinical laboratory evaluations [ Time Frame: Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin ]
  • Findings from vital signs measurements [ Time Frame: Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin ]
  • Findings from physical examinations [ Time Frame: Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin ]
  • Evaluation of Survival data [ Time Frame: At a time point to be determined by the sponsor at a later date ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Assess the Potential Effects of Ketoconazole on the Pharmacokinetics of Trabectedin in Patients With Advanced Malignancies
Official Title  ICMJE An Open-Label, Multicenter Study to Assess the Potential Effects of Ketoconazole on the Pharmacokinetics of Trabectedin in Subjects With Advanced Malignancies
Brief Summary The purpose of this study is to evaluate the potential effects of ketoconazole on blood levels of trabectedin after administration to patients with advanced malignancies.
Detailed Description This is an open-label study (patients will know the names of the study drugs they receive), randomized (patients will be assigned 1 of 2 treatment sequences by chance) that is designed to examine the pharmacokinetics (blood levels) of trabectedin when coadministered with ketoconazole in patients with advanced malignancies. Study drugs include trabectedin and ketoconazole. Trabectedin is a drug being developed to treat patients with cancer that will be administered intravenously (IV) through a catheter (tube) into a central vein over a period of 3 hours once every 21 days with and without ketoconazole. Ketoconazole is an antifungal agent taken as tablets orally (by mouth), that may interfere with the metabolism of trabectedin. In addition, dexamethasone or equivalent steroid, a drug used to prevent nausea and vomiting in chemotherapy patients that may have protective effects on the liver, will be administered to patients before the administration of trabectedin in each treatment cycle. This study will consist of 2 parts, Part A and B. In Part A, trabectedin+ketoconazole followed by trabectedin alone will be administered with ketoconazole to 4 patients to evaluate safety. If the safety and PK data collected in Part A is deemed acceptable, enrollment in Part B of the study will begin and patients will receive 1 of 2 treatment sequences of trabectedin and ketoconazole. Patients in Part A and Part B who complete the treatment phase of the study or who are discontinued due to ketoconazole toxicity, and who in the opinion of the investigator would derive an overall clinical benefit from further treatment with trabectedin will have the opportunity to continue treatment with trabectedin in the optional extension phase. The dose and schedule of trabectedin may be modified by the treating physician in the optional extension phase to be more appropriate for the type of malignancy being treated. Patients will receive 20 mg of IV dexamethasone or equivalent steroid prior to trabectedin administration in all cycles. Part A consists of ketoconazole 200mg 2x daily+trabectedin 0.2mg/m2 i.v. followed 21 days later by trabectedin 1.3mg/m2 i.v. Part B consists of Sequence 1 (ketoconazole 200mg 2x daily+trabectedin 0.2mg/m2 i.v.followed 21 days later by trabectedin 1.3mg/m2 i.v.) and Sequence 2 (trabectedin 1.3mg/m2 i.v followed 21 days later by ketoconazole 200mg 2x daily+trabectedin 0.2mg/m2 i.v). Dexamethasone 20mg i.v. or equivalent, will be given 30 minutes before trabectedin in each cycle.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neoplasm Metastases
Intervention  ICMJE
  • Drug: Trabectedin
    Patients will receive trabectedin 1.3 mg/m2 when given alone and 0.2mg/m2 when given with ketoconazole, intravenously (into a vein) for 3-hour.
  • Drug: Ketoconazole
    Patients will receive ketoconazole 1 X 200 mg tablet, two times a day, orally (by mouth)
  • Drug: Dexamethasone or equivalent steroid
    Patients will receive dexamethasone 20 mg or equivalent steroid intravenously, 30 minutes before trabectedin in each cycle.
Study Arms  ICMJE
  • Experimental: Part 1
    Patients will receive trabectedin+ketoconazole followed by trabectedin alone. Each cycle will be will be separated by 21 days. Patients will receive 6 total consecutive doses of ketoconazole. Dexamethasone or equivalent steroid will be administered before trabectedin in each cycle.
    Interventions:
    • Drug: Trabectedin
    • Drug: Ketoconazole
    • Drug: Dexamethasone or equivalent steroid
  • Experimental: Part 2
    Patients will receive 1 of 2 treatment sequences; Sequence 1: trabectedin+ketoconazole followed by trabectedin alone or Sequence 2: trabectedin alone followed by trabectedin+ketoconazole. Each cycle will be separated by 21 days. Patients will receive 15 total consecutive doses of ketoconazole. Dexamethasone or equivalent steroid will be administered before trabectedin in each cycle.
    Interventions:
    • Drug: Trabectedin
    • Drug: Ketoconazole
    • Drug: Dexamethasone or equivalent steroid
Publications * Machiels JP, Staddon A, Herremans C, Keung C, Bernard A, Phelps C, Khokhar NZ, Knoblauch R, Parekh TV, Dirix L, Sharma S. Impact of cytochrome P450 3A4 inducer and inhibitor on the pharmacokinetics of trabectedin in patients with advanced malignancies: open-label, multicenter studies. Cancer Chemother Pharmacol. 2014 Oct;74(4):729-37. doi: 10.1007/s00280-014-2554-1. Epub 2014 Aug 7.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 18, 2013)
12
Original Estimated Enrollment  ICMJE
 (submitted: December 23, 2010)
11
Actual Study Completion Date  ICMJE November 2012
Actual Primary Completion Date November 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with locally advanced or metastatic disease, any solid tumor except hepatocellular carcinoma (cancer of the liver), who have been 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

Exclusion Criteria:

  • Patients with previous exposure to trabectedin
  • Patients with cancer that has metastasized (spread) to the central nervous system
  • Patients with known liver disease
  • Patients who had a myocardial infarct (heart attack) within 6 months before enrollment or who have any other clinically significant or unstable medical condition as assessed by the Investigator
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01267084
Other Study ID Numbers  ICMJE CR017539
ET743OVC1003 ( Other Identifier: Janssen Research & Development, LLC )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Janssen Research & Development, LLC
Study Sponsor  ICMJE Janssen Research & Development, LLC
Collaborators  ICMJE PharmaMar
Investigators  ICMJE
Study Director: Janssen Research & Development, LLC C. Clinical Trial Janssen Research & Development, LLC
PRS Account Janssen Research & Development, LLC
Verification Date October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP