Phase 1, open-label, parallel group, PK, safety and tolerability study in patients with an advanced solid tumor and either normal hepatic function (Group 1, n = 8) or moderate hepatic impairment (Group 2, n = 8) according to the NCI-ODWG criteria. Patients in Group 1 and Group 2 may be enrolled in parallel, with preferential enrollment of Group 2 patients before Group 1 patients. The study will consist of 2 parts: a single-dose PK part (Part I) and a continuous rucaparib treatment part (Part II).
In Part I, eligible patients will receive a single oral dose of 600 mg rucaparib followed by intensive plasma PK sampling up to Day 7 (hour 144). In Part II, patients may continue to receive continuous oral rucaparib in 28 day cycles. The starting dose for all Group 1 patients will be 600 mg BID. The first 2 patients with moderate hepatic impairment (Group 2) that enter Part II will receive a starting dose of 400 mg BID rucaparib; a lower dose of rucaparib may also be set based on PK results observed in Part I. If this initial starting dose is determined to be safe and tolerable as determined by real-time PK data and dose limiting toxicities (DLT) observed during the first 28 days of rucaparib, the starting dose of rucaparib may be increased in subsequent Group 2 patients. The starting dose for Group 2 patients may also be lowered, based on the patients' real time PK and emerging safety data. The Sponsor and key clinical research organization (CRO) staff will review available adverse event, laboratory, and PK data to determine the starting dose for subsequent Group 2 patients, as well as allowing intra-patient dose escalation of rucaparib after Cycle 1.Treatment with rucaparib will continue until progression of disease, unacceptable toxicity, death, loss to follow-up, withdrawal of consent, or other appropriate clinical reason for discontinuation.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
16
In Part I, eligible patients will receive a single oral dose of 600 mg rucaparib followed by intensive plasma PK sampling up to Day 7 (hour 144). In Part II, patients may continue to receive continuous oral rucaparib in 28 day cycles.
Wojewódzki Szpital Specjalistyczny w Białej Podlaskiej
Biała Podlaska, Poland
Med Polonia Sp. z o.o.
Poznan, Poland
Zachodniopomorskie Centrum Onkologii w Szczecinie
Szczecin, Poland
BioVirtus Centrum Medyczne
Warsaw, Poland
Maximum plasma rucaparib concentration (Cmax)
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Time frame: day 1 to day 7
Area under the plasma rucaparib concentration-time curve from time zero up to the last time point with quantifiable concentration (AUC0-last)
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Time frame: day 1 to day 7
Area under the plasma rucaparib concentration-time curve from time zero up to time infinity (AUC0-inf)
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Time frame: day 1 to day 7
Terminal half-life (t1/2) of rucaparib
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Time frame: day 1 to day 7
Time to attain maximum plasma rucaparib concentration (Tmax)
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Time frame: day 1 to day 7
Apparent clearance (CL/F) of rucaparib
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Time frame: day 1 to day 7
Apparent volume of distribution during terminal phase (Vz/F) of rucaparib
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Time frame: day 1 to day 7
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Summit Clinical Research s.r.o.
Bratislava, Slovakia
Northern Centre for Cancer Care
Newcastle upon Tyne, United Kingdom
Trough plasma concentration of rucaparib at steady state (Cmin,ss)
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Time frame: approximately 4 months
Renal clearance (CLR) of rucaparib
PK parameter of rucaparib to be calculated from the plasma and urine concentration-time data
Time frame: day 1 to day 2
Cumulative amount of rucaparib excreted in urine during urine collection period post rucaparib dose
PK parameter of rucaparib to be calculated based on urine concentration-time data
Time frame: day 1 to day 2
Fraction of administered rucaparib excreted into urine (Fe/F) during urine collection period post rucaparib dose
PK parameter of rucaparib to be calculated based on the amount of rucaparib recovered in urine
Time frame: day 1 to day 2
Incidence of Adverse Events [Safety and Tolerability]
Time frame: From Day 1 to last patient visit in Part II (approximately 2 years)
Incidence of clinical laboratory abnormalities [Safety and Tolerability]
Time frame: From Day 1 to last patient visit in Part II (approximately 2 years)
Incidence of dose modifications [Safety and Tolerability]
Time frame: From Day 1 to last patient visit in Part II (approximately 2 years)