Neoplasm MetastasesPhase 1/2NCT01267084
A Study to Assess the Potential Effects of Ketoconazole on the Pharmacokinetics of Trabectedin in Patients With Advanced Malignancies
A Phase 1/2 study testing Trabectedin, Ketoconazole and Dexamethasone or equivalent steroid in people with Neoplasm Metastases, run by Janssen Research & Development, LLC at 2 sites in Belgium.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasm Metastases
- What is being tested?
- Trabectedin, Ketoconazole and Dexamethasone or equivalent steroid
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesBelgium
- Study dates
- Feb 2011to Nov 2012
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: An Open-Label, Multicenter Study to Assess the Potential Effects of Ketoconazole on the Pharmacokinetics of Trabectedin in Subjects With Advanced Malignancies
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.
Read the 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.
- Conditions
- Neoplasm Metastases
- Being tested
- Trabectedin, Ketoconazole, Dexamethasone or equivalent steroid
- Keywords
- Trabectedin (YONDELIS), Ketoconazole, Antineoplastic Agents, Solid tumors, Locally advanced or metastatic disease, Chemotherapy, Pharmacokinetics
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrabectedinDrug
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.
KetoconazoleDrug
Patients will receive ketoconazole 1 X 200 mg tablet, two times a day, orally (by mouth)
Dexamethasone or equivalent steroidDrug
Patients will receive dexamethasone 20 mg or equivalent steroid intravenously, 30 minutes before trabectedin in each cycle.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Trabectedin; Drug: Ketoconazole; Drug: Dexamethasone or equivalent steroid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics of trabectedin
Measured: 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.
Measured: 1 day during Sequence 1 or Sequence 2 after ketoconazole is coadministered with trabectedin
Secondary outcomes (5)
Number of patients with adverse events
Measured: Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin
Findings from clinical laboratory evaluations
Measured: Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin
Findings from vital signs measurements
Measured: Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin
Findings from physical examinations
Measured: Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin
Evaluation of Survival data
Measured: At a time point to be determined by the sponsor at a later date
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2010 (estimated)
- Study startFeb 2011
- Primary completionNov 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neoplasm MetastasesStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PharmaMar
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC C. Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01267084
- Sponsor's protocol ID
- CR017539
- Other IDs
- ET743OVC1003
- Status last verified
- Oct 2015
- First submitted
- 23 Dec 2010
- Last updated
- 14 Oct 2015
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 25100135
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Multicenter Study to Assess the Potential Effects of Ketoconazole on the Pharmacokinetics of Trabectedin in Subjects With Advanced Malignancies
- ClinicalTrials.gov ID
- NCT01267084
- Acronym / sponsor ID
- CR017539
- Conditions
- Neoplasm Metastases
- Keywords
- Trabectedin (YONDELIS), Ketoconazole, Antineoplastic Agents, Solid tumors, Locally advanced or metastatic disease, Chemotherapy, Pharmacokinetics
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Collaborators
- PharmaMar
- Study start
- Feb 2011
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 24 Dec 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part 1 | Experimental | Drug: Trabectedin, Drug: Ketoconazole, Drug: Dexamethasone or equivalent steroidPatients 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. |
| Part 2 | Experimental | Drug: Trabectedin, Drug: Ketoconazole, Drug: Dexamethasone or equivalent steroidPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TrabectedinPatients 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 | Part 1, Part 2 |
| KetoconazolePatients will receive ketoconazole 1 X 200 mg tablet, two times a day, orally (by mouth) | Drug | Part 1, Part 2 |
| Dexamethasone or equivalent steroidPatients will receive dexamethasone 20 mg or equivalent steroid intravenously, 30 minutes before trabectedin in each cycle. | Drug | Part 1, Part 2 |
Primary outcome
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.
5 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2015.
- Derived from this study: PubMed 25100135Machiels 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.
- An Open-Label, Multicenter Study to Assess the Potential Effects of Ketoconazole on the Pharmacokinetics of Trabectedin in Subjects with Advanced MalignanciesLink provided by the sponsor.
Related trials for Neoplasm Metastases
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingObservational study
A Non-Interventional Study PASS to Characterize Secondary Malignancies of Tcell Origin Following Tisagenlecleucel Therapy
Secondary Malignancies of T-cell Origin
Not yet recruiting
Augmented-Reality ICG Fluorescence Second-Look for Residual Nodal Disease After Axillary Dissection in Breast Cancer
Breast Cancer, Breast Neoplasms
Not yet recruitingPhase 1
GK01 Cell Therapy in Gastric Cancer With Peritoneal Metastasis
Gastric Cancer (GC)
RecruitingObservational study
Real-world Evaluation of the HistoSonics Edison System for Treatment of Liver Tumors Across Multidisciplinary Users (BOOMBOX: Master Study)
Liver Neoplasms, Primary Liver Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen Research & Development, LLC C. Clinical Trial study director
Janssen Research & Development, LLC
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Trabectedin, Ketoconazole and Dexamethasone or equivalent steroid in people with Neoplasm Metastases, run by Janssen Research & Development, LLC at 2 sites in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01267084, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2015.