Primary objective• To assess the effect of cytochrome P450 3A4 enzyme (CYP3A4) induction by rifampicin on the pharmacokinetics (PK) of eribulin following intravenous (IV) administrationSecondary objectives• To assess the safety of eribulin when co-…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacokinetic - Primary Endpoint:
PK parameters AUC0-* and Cmax for eribulin will be estimated in the
presence and absence of rifampicin. PK parameters will be calculated
by non-compartmental analysis of the plasma concentration-time data.
Secondary outcome
Adverse Events both by means of laboratory reserach and by means of physical
research and information of the patient.
Background summary
Because eribulin is metabolized by CYP3A4, it is potentially subject to
interaction with
compounds that are known to either inhibit or induce CYP3A4. This study is
designed to assess
the effect of CYP3A4 induction on the PK of eribulin, by use of the model
inducer rifampicin as
recommended by regulatory guidelines.
Study objective
Primary objective
• To assess the effect of cytochrome P450 3A4 enzyme (CYP3A4) induction by
rifampicin on the pharmacokinetics (PK) of eribulin following intravenous
(IV) administration
Secondary objectives
• To assess the safety of eribulin when co-administered with rifampicin
• To further assess the safety and activity of eribulin as a single agent
Study design
Open-label, non-randomized, crossover study. The study will consist of 3
phases: Pre-Treatment, Treatment, and Extension. Pre-Treatment Phase will
have 2 periods: Screening and Baseline. Treatment Phase will consist of
intensive PK assessment with eribulin given IV alone on Day 1 followed by
eribulin given IV on Day 15 with rifampicin given orally from Days 9 to 20.
Extension Phase allows eribulin treatment to continue for subjects without
progressive disease or unacceptable toxicity.
Intervention
NA
Study burden and risks
Investigational drug: Eribulin mesylate
Cycle 1:
• Eribulin administration as a 2 to 5 minute IV infusion at 1.4 mg/m2
on Day 1 and Day 15
• Rifampicin 600 mg administration orally once a day, from Day 9
to Day 20 of this 28-day cycle
Subsequent Cycles:
• Eribulin administration as a 2 to 5 minute IV infusion at 1.4 mg/m2
on Day 1 and Day 8 of a 21-day cycle
Treatment Phase:
The first cycle will last approximately 28 days
(4 weeks).
Extension Phase: Subjects may continue to receive eribulin at a dose
of 1.4 mg/m2 on Days 1 and 8 of each 21-day cycle as long as the
Investigator considers eribulin therapy to be clinically appropriate.Rifampicin
is an active bactericidial antituberculosis drug which is particularly active
against the
rapidly growing extracellular organisms and also has bactericidial activity
intracellularly.
Rifampicin has activity against slow and intermittently-growing M. Tuberculosis.
Rifampicin inhibits DNA-dependent RNA polymerase activity in susNausea,
vomiting, abdominal pain, pruritus, headache and increasing lethargy will
probably occur within a short time after acute ingestion; unconsciousness may
occur when there is severe hepatic disease. Transient increases in liver
enzymes and/or bilirubin may occur. Brownish-red or
orange colouration of the skin, urine, sweat, saliva, tears and faeces will
occur, and its intensity is
proportional to the amount ingested. Facial or periorbital oedema has also been
reported in
paediatric patients. Hypotension, sinus tachycardia, ventricular arrhythmias,
seizures and cardiac
arrest were reported in some fatal cases.
Mosquito Way Hatfield
Hertfordshire AL10 9SN
GB
Mosquito Way Hatfield
Hertfordshire AL10 9SN
GB
Listed location countries
Age
Inclusion criteria
• 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)
• Adequate renal function as evidenced by serum creatinine
<= 2.0 mg/dL (<= 176 µmol/L) or calculated creatinine clearance
>= 40 mL/minute per the Cockcroft and Gault formula
• Adequate liver function as evidenced by bilirubin <= 1.5 times the
upper limit of normal (ULN) and alkaline phosphatase (ALP),
alanine transaminase (ALT), and aspartate transaminase (AST)
<= 3 times the ULN (in the case of liver metastasis <= 5 times
ULN). In case ALP > 3 times the ULN (in the absence of liver
metastasis) or > 5 times the ULN (in the presence of liver
metastasis), and the subject is also known to have bone
metastasis, the liver specific ALP must be separated from the total
and used to assess the liver function instead of the total ALP.
- Age >=18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
Exclusion criteria
• Subjects with a hypersensitivity to halichondrin B and/or
halichondrin B chemical derivative or a hypersensitivity to
rifampicin
• Subjects with prior participation in an eribulin clinical study, even
if not previously assigned to eribulin treatment
• Subjects with pre-existing neuropathy > Grade 2
• Subjects receiving any medication, dietary supplements or other
compounds or substances known to inhibit or induce CYP3A4 at
the time the study starts
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-013430-24-NL |
| CCMO | NL29143.031.09 |