Trial Information

A Phase 1 Pharmacokinetic and Safety Study of Paclitaxel Injection Concentrate for Nano-dispersion (PICN) Alone and in Combination With Carboplatin in Subjects With Advanced Solid Malignancies

This is a phase I study of PICN alone and in combination with carboplatin in subjects with
advanced solid malignancies. It will be conducted as a two-part study (Part A followed by
Part B).

Part A will characterize the pharmacokinetic profile of PICN at 3 dose levels administered
as 30-min infusion to separate groups of 3 subjects.

Part B will start upon completion of Part A and will use the standard '3+3' dose-escalation
design to determine the Maximum Tolerated Dose (MTD) and recommend phase II dose of PICN in
combination with carboplatin. Both PICN and carboplatin will be administered on day 1 and
will repeat every 3 weeks (1 cycle). Carboplatin dose is fixed at AUC 6 and PICN will be
administered at escalating doses till Dose Limiting Toxicity (DLT) is observed. The dose
escalation plan is as follows: 3 subjects will be treated at the initial dose level for PICN
with carboplatin at AUC 6. If no cycle-1 dose-limiting toxicities (DLTs) are observed, 3
additional subjects will be treated at the next dose level. If one of 3 subjects experiences
a DLT at any given dose level, 3 additional subjects will be treated at that same dose. If a
DLT occurred in at least 2 subjects at any dose level, dose escalation will be halted, and
the next 3 subjects enrolled will be treated at the preceding lower dose level. MTD will be
defined as the dose below which DLT is seen for ≥ 2 subjects in cycle 1. At least 6
subjects will be treated at the MTD. 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. Subjects will continue therapy until
disease progression, development of unacceptable toxicities, non-compliance, intercurrent
illness that prevents treatment continuation, withdrawal of consent, or change in subject
condition that render the subject unacceptable for further treatment. 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 PK studies will be collected at pre-planned
time-points.