A Phase 1b Study to Assess the Safety of PLX3397 and Paclitaxel in Patients With Advanced Solid Tumors
This is a nonrandomized, open label phase 1b study employing a standard 3+3 sequential dose
escalation design to determine the maximum tolerated dose (MTD) of PLX3397, a novel
inhibitor of the CSF-1 receptor (Fms), when administered in combination with paclitaxel in
patients with advanced, incurable solid tumors. Treatment with PLX3397 will consist of oral
administration with the starting dose of 600 mg/day for 28 days. Paclitaxel will be
administered once weekly over approximately 60 minutes in each 28-day treatment cycle. The
planned cohorts are Cohort 1: 600 mg/day; Cohort 2: 800 mg/day; and Cohort 3: 1000 mg/day.
Each dose level cohort will enroll 3-6 patients. Enrollment into the next higher dose level
will begin only if the first 3 patients enrolled into the cohort complete the 28-day
observation period without the occurrence of a Dose-Limiting Toxicity (DLT). If one of the
3 initial patients at a given dose level experiences a DLT, the cohort at this dose level
will be expanded to include an additional 3 patients (6 patients total).
If ≥ 2/6 patients experience a DLT, then dose escalation will be stopped and the preceding
dose level will be considered the MTD.
Enrollment is planned to include approximately 30 patients recruited from approximately 3-4
sites. The total number of patients to be enrolled will depend on the number of cohorts and
whether a cohort requires 3 or 6 patients. During the first cycle, a patient that does not
receive at least 21 days of PLX3397 or does not receive at least 3 of 4 doses of paclitaxel
for reasons other than a DLT, the patient may be replaced.
Study treatment will be provided until disease progression, unacceptable or dose-limiting
toxicity, death, withdrawal of consent, study termination by Sponsor, or if the Investigator
and patient agree that it is in the patient's best interests to discontinue.
The primary objective of this phase 1b study is to establish the DLT and MTD of PLX3397 when
given in combination with weekly standard dose Paclitaxel.
The secondary objectives include (1) evaluation of overall safety and tolerability of
PLX3397 in combination with paclitaxel, (2) explore the efficacy of PLX3397 in combination
with paclitaxel in patients with advance solid tumors, and (3) determine the PK of PLX3307
when administered in combination with paclitaxel.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety--Subject incidence of adverse events
Subjects will take oral doses of PLX3397 twice a day using a continuous dosing regimen. Paclitaxel IV will be administered weekly in each 28-day treatment cycle. Physical exminations, vital signs, 12-lead electrocardiograms (ECG), adverse events, hematology, and serum chemistry will be used to assess safety throughout the study. Adverse events will be monitored and reviewed for safety issues/abnormal changes in the above mentioned tests.
United States: Food and Drug Administration
|UCSF||San Francisco, California 941430324|
|University Hospitals of Cleveland||Cleveland, Ohio 44106|
|Ohio State University||Columbus, Ohio 43210|