A Phase 1 Pharmacokinetic (PK), Safety, and Tolerability Study of Paclitaxel Injection Concentrate for Nano-dispersion (PICN) Administered Weekly in Subjects With Advanced Solid Malignancies in US Population.
This is a phase I study of PICN that will use the standard '3+3'dose-escalation design to
determine the MTD and recommend phase II dose of PICN administered once a week for 3 weeks,
followed by 1 week of rest. PICN will be administered as 30-minute intravenous infusion on
days 1, 8, and 15 of each 4-week cycle - once a week for 3 weeks, followed by 1 week of rest
(one cycle). Next cycle dosing will open on day 28 after laboratory investigations are done
of the previous cycle. Subjects will continue therapy until disease progression, development
of unacceptable toxicities, non-compliance, inter-current illness that prevents treatment
continuation, withdrawal of consent, or change in patient condition that render the patient
unacceptable for further treatment. There are 6 dose levels planned for dose escalation. The
dose escalation plan is as follows: Three subjects will be treated at the initial dose level
for PICN. If no Cycle-1 dose-limiting toxicities (DLTs) are observed, 3-new subjects will be
treated at the next dose level. If one of three subjects experiences a DLT at any given dose
level, three additional subjects will be treated at that same dose. If a DLT occurred in at
least two subjects at any dose level, dose escalation will be halted, and the next three
subjects enrolled will be treated at the preceding lower dose level. MTD will be defined as
the highest PICN dose at which DLT (Dose Limiting Toxicity) is seen in <2 subjects out of 6.
Subjects who fail to complete 1 cycle of study treatment for non-treatment related reasons
will be replaced.
AEs will be monitored across all cycles per CTCAE 4.0 and disease response will be assessed
by imaging at baseline and on day 1 of cycle 3, 5, and 7 as per RECIST 1.1. Upon study
completion, subjects will be followed for toxicities for 4 weeks, or longer if there are
unresolved ≥ grade 3 toxicities at the end of the 4-week period. Subjects removed from study
for unacceptable adverse events will be followed until resolution (≤ grade 2) or
stabilization of the adverse events. Blood samples for pharmacokinetic studies will be
collected at pre-planned time-points.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determination of Maximum Tolerated Dose (MTD) during dose escalation
MTD for PICN will be determined as dose below the dose at which DLT (Dose Limiting Toxicity) is seen for ≥ 2 subjects
One 21-day treatment cycle
Wen Wee Ma, M.D.
Assistant Professor, Roswell Park Cancer Institute
United States: Food and Drug Administration
|Roswell Park Cancer Institute||Buffalo, New York 14263|