A Study to Assess the Potential Effects of Ketoconazole on the Pharmacokinetics of Trabectedin in Patients With Advanced Malignancies
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
The purpose of this study is too evaluate the potential effects of ketoconazole on blood levels of tradbectedin after administration to patients with advanced malignancies.
| Condition | Intervention | Phase |
|---|---|---|
|
Neoplasm Metastases |
Drug: Part B, Sequence 2 Drug: Part A Drug: Part B, Sequence 1 |
Phase 1 |
| 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 |
- 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 and Sequence 2 after ketoconazole is coadministered with trabectedin ] [ Designated as safety issue: No ]
- 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: No ]
- 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: 002
Part B Sequence 1 1 ketoconazole 200 mg tablet 12 hrs before and immediately prior to trabectedin 0.2 mg/m2 i.v. on Day 1 cycle 1 + 1 ketoconazole tablet 2x daily to Day 7 followed 21 days later by trabectedin 1.3 mg/m2 i.v. on Day 1 cycle 2.Dexamethasone administered 30 minutes prior to trabectedin in each cycle.
|
Drug: Part B, Sequence 1
1 ketoconazole 200 mg tablet 12 hrs before and immediately prior to trabectedin 0.2 mg/m2 i.v. on Day 1, cycle 1 + 1 ketoconazole tablet 2x daily to Day 7 followed 21 days later by trabectedin 1.3 mg/m2 i.v. on Day 1, cycle 2.Dexamethasone administered 30 minutes prior to trabectedin in each cycle.
|
|
Experimental: 003
Part B Sequence 2 Trabectedin 1.3 mg/m2 i.v. on Day 1 cycle 1 followed 21 days later by 1 ketoconazole 200 mg tablet 12 hrs before and immediately prior to trabectedin 0.2 mg/m2 i.v. on Day 1 cycle 2 + 1 ketoconazole tablet 2x daily to Day 7. Dexamethasone administered 30 minutes prior to trabectedin in each cycle.
|
Drug: Part A
1 ketoconazole 200-mg tablet 12 hrs before and immediately prior to trabectedin 0.2 mg/m2 i.v. on Day 1 + 1 ketoconazole tablet 2x daily to Day 3 followed 21 days later by trabectedin 1.3mg/m2 i.v. Dexamethasone will be administered 30 minutes prior to trabectedin.
Drug: Part B, Sequence 2
Trabectedin 1.3 mg/m2 i.v. on Day 1, cycle 1 followed 21 days later by 1 ketoconazole 200 mg tablet 12 hrs before and immediately prior to trabectedin 0.2 mg/m2 i.v. on Day 1, cycle 2 + 1 ketoconazole tablet 2x daily to Day 7. Dexamethasone administered 30 minutes prior to trabectedin in each cycle.
|
|
Experimental: 001
Part A 1 ketoconazole 200-mg tablet 12 hrs before and immediately prior to trabectedin 0.2 mg/m2 i.v. on Day 1 + 1 ketoconazole tablet 2x daily to Day 3 followed 21 days later by trabectedin 1.3mg/m2 i.v. Dexamethasone will be administered 30 minutes prior to trabectedin.
|
Drug: Part B, Sequence 2
Trabectedin 1.3 mg/m2 i.v. on Day 1, cycle 1 followed 21 days later by 1 ketoconazole 200 mg tablet 12 hrs before and immediately prior to trabectedin 0.2 mg/m2 i.v. on Day 1, cycle 2 + 1 ketoconazole tablet 2x daily to Day 7. Dexamethasone administered 30 minutes prior to trabectedin in each cycle.
Drug: Part A
1 ketoconazole 200-mg tablet 12 hrs before and immediately prior to trabectedin 0.2 mg/m2 i.v. on Day 1 + 1 ketoconazole tablet 2x daily to Day 3 followed 21 days later by trabectedin 1.3mg/m2 i.v. Dexamethasone will be administered 30 minutes prior to trabectedin.
|
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) and to assess survival and safety of trabectedin when coadministered with ketoconazole in patients with advanced malignancies. Study drugs include trabectedin and ketoconazole. Trabectdin is a drug being developed to treat patients with cancer that will be administered intravenously (i.v.) 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 that may interfere with the action of trabectedin when taken orally (by mouth) as tablets. In addition, dexamethosone, 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 will be administered with ketoconazole to 3 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 i.v. dexamethasone (or its equivalent) 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 |
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| Belgium | |
| Brussels, Belgium | |
| Wilrijk, Belgium | |
| Study Director: | Janssen Research & Development, LLC C. Clinical Trial | Janssen Research & Development, LLC |
More 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: | March 11, 2013 |
| 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 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 14-alpha Demethylase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antifungal Agents Anti-Infective Agents Antineoplastic Agents, Alkylating Alkylating Agents |
ClinicalTrials.gov processed this record on May 19, 2013