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

This study has been completed.
Sponsor:
Collaborator:
PharmaMar
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01267084
First received: December 23, 2010
Last updated: April 23, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Neoplasm Metastases
Drug: Trabectedin
Drug: Ketoconazole
Drug: Dexamethasone or equivalent steroid
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter Study to Assess the Potential Effects of Ketoconazole on the Pharmacokinetics of Trabectedin in Subjects With Advanced Malignancies

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Pharmacokinetics of ketoconazole [ Time Frame: 1 day during Sequence 1 or Sequence 2 after ketoconazole is coadministered with trabectedin ] [ Designated as safety issue: No ]
    This will be measured when ketoconazole will be administered.


Secondary Outcome Measures:
  • Number of patients with adverse events [ Time Frame: Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin ] [ Designated as safety issue: Yes ]
  • Findings from clinical laboratory evaluations [ Time Frame: Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin ] [ Designated as safety issue: No ]
  • Findings from vital signs measurements [ Time Frame: Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin ] [ Designated as safety issue: No ]
  • Findings from physical examinations [ Time Frame: Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin ] [ Designated as safety issue: No ]
  • Evaluation of Survival data [ Time Frame: At a time point to be determined by the sponsor at a later date ] [ Designated as safety issue: No ]

Enrollment: 12
Study Start Date: February 2011
Study Completion Date: February 2013
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
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.
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01267084

Locations
Belgium
Brussels, Belgium
Wilrijk, Belgium
Sponsors and Collaborators
Janssen Research & Development, LLC
PharmaMar
Investigators
Study Director: Janssen Research & Development, LLC C. Clinical Trial Janssen Research & Development, LLC
  More Information

Additional Information:
No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01267084     History of Changes
Other Study ID Numbers: CR017539, ET7430VC1003
Study First Received: December 23, 2010
Last Updated: April 23, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Janssen Research & Development, LLC:
Trabectedin (YONDELIS)
Ketoconazole
Antineoplastic Agents
Solid tumors
Locally advanced or metastatic disease
Chemotherapy
Pharmacokinetics

Additional relevant MeSH terms:
Neoplasms
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes
Trabectedin
Antineoplastic Agents
Dexamethasone
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Ketoconazole
Therapeutic Uses
Pharmacologic Actions
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014