Evaluation of the Safety, Pharmacokinetics and Efficacy of Four Doses of YN968D1 in Subjects With Solid Tumors
Part 1 will include a sequential evaluation of 3 subjects per cohort; cohort 1 at a dose of
100 mg YN968D1, followed by a cohorts 2, 3 and 4 at doses of 250 mg, 500 mg and 750 mg
respectively. Initially, each subject will receive one dose of YN968D1 followed by an
observation period at least 7 days, during which single dose PK assessments and safety
monitoring will be performed. If the initial dose is well tolerated, the subject will return
on Day 8 and receive up to 28-Days of continuous YN968D1 oral administration daily. Each
subject will subsequently be assessed for safety and disease progression on Day 35±2 and
steady state pharmacokinetic sampling will be obtained. Patients may continue on therapy for
an additional cycles up to 28-Days without dose interruption if the therapy is well
tolerated. Efficacy assessments (biomarkers) and disease progression (RECIST imaging) will
be assessed every two 28-Day cycles (±3 days). The subjects will be assessed for safety for
at least 28-Days after the last dose of YN968D1.
For Part 1 of this study, a Dose Limiting Toxicity (DLT) event is defined as any of the
following events that are assessed by the Investigator as probably or possibly related to
YN968D1 and occur during or after the initial dose on Day 1 through Day 35 (±3) of the first
cycle of therapy. DLT is defined as:
- CTCAE Grade 4 event
- Grade 3 febrile neutropenia (<1,000 neutrophils/mL)
- Grade 3 hematologic toxicity with duration > 7 days
- Grade 3 non-hematologic toxicity (except for nausea, vomiting, diarrhea that continues
despite optimal medical management)
If a DLT is experienced in any cohort, the cohort will be expanded to 6 subjects. If two (2)
DLTs are experienced in any cohort, the study will be paused until the safety events are
evaluated and discussed with the FDA to determine if the trial may continue.
Part 2 of this study will include up to 30 subjects. Each subject will receive a 750 mg dose
or the maximum tolerated dose of YN968D1 from part 1 of the study for up to 28-Days
continuous cycles of therapy. If a subject experiences an intolerable side effect a dose
reduction or a dose interruption for up to Days is allowed at the discretion of the
investigator. Subjects will be evaluated for RECIST (version 1.1) response at the end of the
second cycle of therapy on Day 56±3 of the Part 2 study. Safety reporting will be continued
for up to 28-Days from the last dose of study medication.
All subjects in Part 1 and 2 of this trial will be eligible to continue therapy provided
they have a least stable disease or better and are, in the opinion of the investigator,
adequately tolerating treatment with YN968D1.
Interventional
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Dose Limiting Toxicity
Dose Limiting Toxicity (DLT) event is defined as any of the following events that are assessed by the Investigator as probably or possibly related to YN968D1 and occur during or after the initial dose on Day 1 through Day 35±3 of the first cycle of therapy. DLT is defined as: CTCAE Grade 4 event Grade 3 febrile neutropenia (<1,000 neutrophils/mL) Grade 3 hematologic toxicity with duration > 7 days Grade 3 non-hematologic toxicity (except for nausea, vomiting, diarrhea that continues despite optimal medical management) If a DLT is experienced in any cohort, the cohort will be expanded to 6 subjects. If two (2) DLTs are experienced in any cohort, the study will be paused until the safety events are evaluated and discussed with the FDA to determine if the trial may continue.
DLT during the first 28-day cycle (±3) of YN968D1 treatment
Yes
Sunil Sharma, MD, FACP
Principal Investigator
Huntsman Cancer Institute
United States: Food and Drug Administration
BK-LSK-AM101
NCT01726101
April 2012
June 2013
Name | Location |
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Huntsman Cancer Institute | Salt Lake City, Utah 84112 |