TumorPhase 1NCT03002493
To Assess the Effect of Rifampicin on the Pharmacokinetics of Eribulin Mesylate in Participants With Advanced Solid Tumors
A Phase 1 study testing Eribulin mesylate and Rifampicin in people with Tumor, run by Eisai Limited at 2 sites in Netherlands.
Trial summary
The primary objective of this study was to assess the effect of cytochrome P450 3A4 enzyme (CYP3A4) induction by rifampicin on the pharmacokinetics (PK) of eribulin mesylate following intravenous (IV) administration in participants with advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tumor
- What is being tested?
- Eribulin mesylate and Rifampicin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 2 sitesNetherlands
- Study dates
- Dec 2009to Jun 2011
- Phase
- Phase 1
- 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
- Histologically or cytologically confirmed advanced solid tumors that have progressed following standard therapy or for which no standard therapy exists (including surgery or radiation therapy)
- Resolution of all chemotherapy or radiation-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy and alopecia Grade 2
- Age greater than or equal to 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
- Life expectancy of greater than or equal to 3 months
- Adequate renal function as evidenced by serum creatinine less than or equal to 2.0 mg/dL (less than or equal to 176 umol/L) or calculated creatinine clearance greater than or equal to 40 mL/minute per the Cockcroft and Gault formula
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- Adequate liver function as evidenced by bilirubin less than or equal to 1.5 times the upper limit of normal (ULN) and alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 times the ULN (in the case of liver metastasis less than or equal to 5 times ULN). In the case ALP greater than 3 times the ULN (in the absence of liver metastasis) or greater than 5 times the ULN (in the presence of liver metastasis), and the participant was also known to have bone metastasis, the liver specific ALP were separated from the total and used to assess the liver function instead of the total ALP
- Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L, hemoglobin greater than or equal to 10.0 g/dL or greater than or equal to 6.2 mmol/L (hemoglobin less than 10.0 g/dL or less than 6.2 mmol/L were acceptable if it were corrected by growth factor or transfusion), and platelets greater than or equal to 100 x 109/L
- Participants were willing and able to comply with the study protocol for the duration of the study
- Written informed consent were obtained prior to any study-specific screening procedures with the understanding that the participant may withdraw consent at any time without prejudice
- Females of childbearing potential with a negative serum beta-Human chorionic gonadotropin or a negative urine pregnancy test at Visit 1 (Screening) and prior to starting study drug(s) (Visit 3). Female participants of childbearing potential who agreed to be abstinent or to use a highly effective method of contraception (eg, condom + spermicide, condom + diaphragm with spermicide, intrauterine device [IUD], or have a vasectomised partner) starting prior to starting study drug, throughout the entire study period and for 30 days after the last dose of study drug. Those women using hormonal contraceptives must also have used an additional approved method of contraception (as described previously). Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential
- Male participants who were not abstinent or have not undergone a successful vasectomy, who were partners of women of childbearing potential must have used, or their partners must have used a highly effective method of contraception (eg, condom + spermicide, condom + diaphragm with spermicide, IUD) starting prior to starting study drug(s) and throughout the entire study period and for 30 days after the last dose of study drug. Those with partners using hormonal contraceptives must also have used an additional approved method of contraception (as described previously)
Who cannot join
- Hypersensitivity to halichondrin B and/or halichondrin B chemical derivatives or a hypersensitivity to rifampicin
- Prior participation in an eribulin clinical study, even if not previously assigned to eribulin treatment
- Preexisting neuropathy greater than Grade 2
- Any of the following treatments within the specified period before eribulin treatment starts:
- chemotherapy, radiation or biological therapy within 2 weeks,
- hormonal therapy within 1 week with the exception of prostate cancer patients who are on medical castration with a gonadotropin-releasing hormone analog,
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- any investigational drug within 4 weeks
- Any medication, dietary supplements or other compounds or substances known to induce or inhibit cytochrome P450 3A4 (CYP3A4) activity at the time the study starts
- Presence of impaired intestinal absorption
- Significant cardiovascular impairment such as history of congestive heart failure greater than Grade II (New York Heart Association [NYHA]), unstable angina or myocardial infarction within the past 6 months, or serious cardiac arrhythmia
- Clinically significant electrocardiograms (ECGs) abnormality, including a marked baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTc interval greater than 500 msec)
- Known positive human immunodeficiency virus (HIV) status
- Brain or subdural metastases, unless they had completed local therapy and had discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment with eribulin
- Presence of meningeal carcinomatosis
- Any history of or concomitant medical condition that, in the opinion of the Investigator, that would have compromise the participant's ability to safely complete the study
Trial locations and contacts
2 sites in 1 country.
Netherlands2 sites
Netherlands Cancer Institute
Amsterdam
University Medical Center Utrecht
Utrecht
About this study
Official title: An Open-Label Phase I Study to Assess the Effect of Rifampicin on the Pharmacokinetics of Eribulin Mesylate (E7389) in Subjects With Advanced Solid Tumors
The primary objective of this study was to assess the effect of cytochrome P450 3A4 enzyme (CYP3A4) induction by rifampicin on the pharmacokinetics (PK) of eribulin mesylate following intravenous (IV) administration in participants with advanced solid tumors. The secondary objectives of this study were to assess the safety of eribulin mesylate when co-administered with rifampicin and assess the safety and activity of eribulin mesylate as a single agent.
Read the detailed description
The study consisted of 3 phases: Pre-Treatment, Treatment, and Extension. Pre-Treatment Phase had 2 periods: Screening and Baseline. Treatment Phase consisted of intensive PK assessment with eribulin mesylate given IV alone on Day 1 followed by eribulin mesylate given IV on Day 15 with rifampicin given orally from Days 9 to 20. Extension Phase allowed eribulin mesylate treatment to continue for participants without progressive disease or unacceptable toxicity.
- Conditions
- Tumor
- Being tested
- Eribulin mesylate, Rifampicin
- Keywords
- Rifampicin, Pharmacokinetics, Eribulin Mesylate, E7389, Advanced Solid Tumors, Tumors
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eribulin mesylateDrug
Also called E7389
Treatment phase: During Cycle 1, eribulin mesylate was administered as a 2 to 5 minute (min) intravenous (IV) infusion at 1.4 mg/m2 on Day 1 and Day 15 of 21-day cycle. During subsequent cycles, eribulin mesylate administration as a 2 to 5 min IV infusion at 1.4 mg/m2 on Day 1 and Day 8 of a 21-day cycle.
Extension phase: Eribulin mesylate was administered continuously as a 2 to 5 min IV infusion at 1.4 mg/m2 on Day 1 and Day 8 of 21-day cycles, as long as the Investigator considered eribulin mesylate therapy to be clinically appropriate.
Eribulin mesylateDrug
RifampicinDrug
Treatment phase: Rifampicin 600 mg was administered orally once a day, from Day 9 to Day 20 of 28-day cycle of Cycle 1.
| Study group | Role | What they receive |
|---|---|---|
| Eribulin mesylate + Rifampicin | Experimental | Not described Receives: Drug: Eribulin mesylate; Drug: Rifampicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best overall tumor response
Measured: From signing of Informed consent until disease progression, undue toxicity, withdrawal by participant, at the discretion of the investigator or up to approximately 8 Months
Area under the concentration-time curve from zero (pre-dose) extrapolated to infinite time (AUC 0-infinity) for eribulin mesylate +/- rifampicin
Measured: Day 1 and Day 15 of Cycle 1 (pre-dose, end of infusion, 15 minute (min), and 30 min, 1, 2, 4, 6, 10, 24, 48, 72, 96, 120 and 144 hours after each eribulin administration)
Maximum observed plasma concentration (Cmax) for eribulin mesylate +/- rifampicin
Measured: Day 1 and Day 15 of Cycle 1 (pre-dose, end of infusion, 15 min and 30 min, 1, 2, 4, 6, 10, 24, 48, 72, 96, 120 and 144 hours after each eribulin administration)
Area under the concentration-time curve from zero (pre-dose) to time of last quantifiable concentration (AUC 0-t) for eribulin mesylate
Measured: Day 1 and Day 15 of Cycle 1 (pre-dose, end of infusion, 15 min and 30 min, 1, 2, 4, 6, 10, 24, 48, 72, 96, 120 and 144 hours after each eribulin administration)
Time of maximum observed plasma concentration (Tmax) for eribulin mesylate
Measured: Day 1 and Day 15 of Cycle 1 (pre-dose, end of infusion, 15 min and 30 min, 1, 2, 4, 6, 10, 24, 48, 72, 96, 120 and 144 hours after each eribulin administration)
Half-life (t1/2) for eribulin mesylate
Measured: Day 1 and Day 15 of Cycle 1 (pre-dose, end of infusion, 15 min and 30 min, 1, 2, 4, 6, 10, 24, 48, 72, 96, 120 and 144 hours after each eribulin administration)
Clearance (CL) for eribulin mesylate
Measured: Day 1 and Day 15 of Cycle 1 (pre-dose, end of infusion, 15 min and 30 min, 1, 2, 4, 6, 10, 24, 48, 72, 96, 120 and 144 hours after each eribulin administration)
Volume of distribution at steady state (Vss) for eribulin mesylate
Measured: Day 1 and Day 15 of Cycle 1 (pre-dose, end of infusion, 15 min and 30 min, 1, 2, 4, 6, 10, 24, 48, 72, 96, 120 and 144 hours after each eribulin administration)
Secondary outcomes (1)
Number of participants with adverse events (AEs) and serious adverse events (SAEs) as a measure of safety
Measured: From date of administration of first dose up to 30 days after the last dose of study treatment, up to approximately 8 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2016 (estimated)
- Study startDec 2009
- Primary completionFeb 2011
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TumorStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03002493
- Sponsor's protocol ID
- E7389-E044-111
- Status last verified
- Feb 2016
- First submitted
- 21 Dec 2016
- Last updated
- 15 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Phase I Study to Assess the Effect of Rifampicin on the Pharmacokinetics of Eribulin Mesylate (E7389) in Subjects With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT03002493
- Acronym / sponsor ID
- E7389-E044-111
- Conditions
- Tumor
- Keywords
- Rifampicin, Pharmacokinetics, Eribulin Mesylate, E7389, Advanced Solid Tumors, Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Eisai LimitedIndustry (pharma, biotech, devices)
- Study start
- Dec 2009
- Primary completion
- Feb 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 23 Dec 2016 (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 primary objective of this study was to assess the effect of cytochrome P450 3A4 enzyme (CYP3A4) induction by rifampicin on the pharmacokinetics (PK) of eribulin mesylate following intravenous (IV) administration in participants with advanced solid tumors. The secondary objectives of this study were to assess the safety of eribulin mesylate when co-administered with rifampicin and assess the safety and activity of eribulin mesylate as a single agent.
Detailed description
The study consisted of 3 phases: Pre-Treatment, Treatment, and Extension. Pre-Treatment Phase had 2 periods: Screening and Baseline. Treatment Phase consisted of intensive PK assessment with eribulin mesylate given IV alone on Day 1 followed by eribulin mesylate given IV on Day 15 with rifampicin given orally from Days 9 to 20. Extension Phase allowed eribulin mesylate treatment to continue for participants without progressive disease or unacceptable toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eribulin mesylate + Rifampicin | Experimental | Drug: Eribulin mesylate, Drug: Rifampicin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histologically or cytologically confirmed advanced solid tumors that have progressed following standard therapy or for which no standard therapy exists (including surgery or radiation therapy)
- Resolution of all chemotherapy or radiation-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy and alopecia Grade 2
- Age greater than or equal to 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
- Life expectancy of greater than or equal to 3 months
Key exclusion criteria (15 listed)
- Hypersensitivity to halichondrin B and/or halichondrin B chemical derivatives or a hypersensitivity to rifampicin
- Prior participation in an eribulin clinical study, even if not previously assigned to eribulin treatment
- Preexisting neuropathy greater than Grade 2
- Any of the following treatments within the specified period before eribulin treatment starts:
- Any medication, dietary supplements or other compounds or substances known to induce or inhibit cytochrome P450 3A4 (CYP3A4) activity at the time the study starts
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 |
|---|---|---|
| Eribulin mesylateAlso: E7389Treatment phase: During Cycle 1, eribulin mesylate was administered as a 2 to 5 minute (min) intravenous (IV) infusion at 1.4 mg/m2 on Day 1 and Day 15 of 21-day cycle. During subsequent cycles, eribulin mesylate administration as a 2 to 5 min IV infusion at 1.4 mg/m2 on Day 1 and Day 8 of a 21-day cycle. Extension phase: Eribulin mesylate was administered continuously as a 2 to 5 min IV infusion at 1.4 mg/m2 on Day 1 and Day 8 of 21-day cycles, as long as the Investigator considered eribulin mesylate therapy to be clinically appropriate. | Drug | Eribulin mesylate + Rifampicin |
| Eribulin mesylate | Drug | Eribulin mesylate + Rifampicin |
| RifampicinTreatment phase: Rifampicin 600 mg was administered orally once a day, from Day 9 to Day 20 of 28-day cycle of Cycle 1. | Drug | Eribulin mesylate + Rifampicin |
Primary outcome
Best overall tumor response
Time frame: From signing of Informed consent until disease progression, undue toxicity, withdrawal by participant, at the discretion of the investigator or up to approximately 8 Months
Area under the concentration-time curve from zero (pre-dose) extrapolated to infinite time (AUC 0-infinity) for eribulin mesylate +/- rifampicin
Time frame: Day 1 and Day 15 of Cycle 1 (pre-dose, end of infusion, 15 minute (min), and 30 min, 1, 2, 4, 6, 10, 24, 48, 72, 96, 120 and 144 hours after each eribulin administration)
Maximum observed plasma concentration (Cmax) for eribulin mesylate +/- rifampicin
Time frame: Day 1 and Day 15 of Cycle 1 (pre-dose, end of infusion, 15 min and 30 min, 1, 2, 4, 6, 10, 24, 48, 72, 96, 120 and 144 hours after each eribulin administration)
Area under the concentration-time curve from zero (pre-dose) to time of last quantifiable concentration (AUC 0-t) for eribulin mesylate
Time frame: Day 1 and Day 15 of Cycle 1 (pre-dose, end of infusion, 15 min and 30 min, 1, 2, 4, 6, 10, 24, 48, 72, 96, 120 and 144 hours after each eribulin administration)
Time of maximum observed plasma concentration (Tmax) for eribulin mesylate
Time frame: Day 1 and Day 15 of Cycle 1 (pre-dose, end of infusion, 15 min and 30 min, 1, 2, 4, 6, 10, 24, 48, 72, 96, 120 and 144 hours after each eribulin administration)
Half-life (t1/2) for eribulin mesylate
Time frame: Day 1 and Day 15 of Cycle 1 (pre-dose, end of infusion, 15 min and 30 min, 1, 2, 4, 6, 10, 24, 48, 72, 96, 120 and 144 hours after each eribulin administration)
Clearance (CL) for eribulin mesylate
Time frame: Day 1 and Day 15 of Cycle 1 (pre-dose, end of infusion, 15 min and 30 min, 1, 2, 4, 6, 10, 24, 48, 72, 96, 120 and 144 hours after each eribulin administration)
Volume of distribution at steady state (Vss) for eribulin mesylate
Time frame: Day 1 and Day 15 of Cycle 1 (pre-dose, end of infusion, 15 min and 30 min, 1, 2, 4, 6, 10, 24, 48, 72, 96, 120 and 144 hours after each eribulin administration)
1 secondary outcome
Number of participants with adverse events (AEs) and serious adverse events (SAEs) as a measure of safety
Time frame: From date of administration of first dose up to 30 days after the last dose of study treatment, up to approximately 8 months.
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 15 Mar 2017.
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Eribulin mesylate and Rifampicin in people with Tumor, run by Eisai Limited at 2 sites in Netherlands.
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 12 inclusion and 15 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 15 Mar 2017. 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 Netherlands. 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 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.
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?
Best overall tumor response (time frame: From signing of Informed consent until disease progression, undue toxicity, withdrawal by participant, at the discretion of the investigator or up to approximately 8 Months). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Mar 2017.