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

NCT01267084 | Completed Phase 1 DMC

• 2 other identifiers: CR017539ET743OVC1003
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

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.

Conditions

Neoplasm Metastases

Keywords

Trabectedin (YONDELIS); Ketoconazole; Antineoplastic Agents; Solid tumors; Locally advanced or metastatic disease; Chemotherapy; Pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetics of trabectedin

  At protocol-specified time points for up to 8 days during each 21-day cycle in Sequence 1 and Sequence 2

• Pharmacokinetics of ketoconazole

  This will be measured when ketoconazole will be administered.

  1 day during Sequence 1 or Sequence 2 after ketoconazole is coadministered with trabectedin

Secondary Outcomes (5)

• Number of patients with adverse events

  Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin

• Findings from clinical laboratory evaluations

  Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin

• Findings from vital signs measurements

  Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin

• Findings from physical examinations

  Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin

• Evaluation of Survival data

  At a time point to be determined by the sponsor at a later date

Study Arms (2)

Part 1

EXPERIMENTAL

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; Drug: Ketoconazole; Drug: Dexamethasone or equivalent steroid

Part 2

EXPERIMENTAL

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; Drug: Ketoconazole; Drug: Dexamethasone or equivalent steroid

Interventions

Trabectedin DRUG

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.

Part 1; Part 2

Ketoconazole DRUG

Patients will receive ketoconazole 1 X 200 mg tablet, two times a day, orally (by mouth)

Part 1; Part 2

Dexamethasone or equivalent steroid DRUG

Patients will receive dexamethasone 20 mg or equivalent steroid intravenously, 30 minutes before trabectedin in each cycle.

Part 1; Part 2

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead
• PharmaMar: collaborator

Study Sites (2)

Unknown Facility

Brussels, Belgium

Location

Unknown Facility

Wilrijk, Belgium

Location

Related Publications (1)

• 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.

  PMID: 25100135 DERIVED

Related Links

• An Open-Label, Multicenter Study to Assess the Potential Effects of Ketoconazole on the Pharmacokinetics of Trabectedin in Subjects with Advanced Malignancies

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Trabectedin; Ketoconazole; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Piperazines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Janssen Research & Development, LLC C. Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2010
• First Posted: December 24, 2010
• Study Start: February 1, 2011
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: October 14, 2015

Record last verified: 2015-10

Locations

BE (2)