A First-In-Human Phase I Study of sEphB4-HSA in Patients With Advanced Solid Tumors With Expansion at the Maximum Tolerated Dose (MTD) or Recommended Phase II Dose (RP2D).
PRIMARY OBJECTIVES:
I. To establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of
sEphB4-HSA.
II. To describe the dose limiting toxicities and adverse event profile of sEphB4-HSA in
patients with advanced solid tumors.
III. To describe the pharmacokinetics of sEphB4-HSA. IV. To describe the anti-tumor activity
of sEphB4-HSA as manifested by responses to treatment.
V. To obtain preliminary evaluation of effect of sEphB4-HSA on absolute circulating tumor
cell (CTC) numbers as compared with pre-treatment levels using pre- and during treatment
CTC. Exploratory evaluation of effect of sEphB4-HSA on downstream protein mediators of the
Ephrin pathway (pAKT, pSrc) and their transcriptional target genes (rgs5 and psenen) will be
performed.
VI. To collect pilot information to identify a dose or doses with biologic activity.
Biologic activity after treatment with sEphB4-HSA will be defined as evidence of
drug-on-target effect as manifested by reduction in absolute CTC numbers. Other exploratory
evaluations of drug-on-target effect such as increase in transcript levels of psenen or rgs5
may be considered in the assessment of biologic activity.
OUTLINE: This is a dose-escalation study. Patients will be assigned to receive recombinant
EphB4-HSA fusion protein intravenously (IV) over 60 minutes in one of the following
treatment schedules:
1. Weekly treatment - administered on days 1, 8, 15, and 22. Courses repeat every 28 days
in the absence of disease progression or unacceptable toxicity.
2. Every 2 weeks treatment - administered on days 1 and 15. Courses repeat every 28 days
in the absence of disease progression or unacceptable toxicity.
3. Every 3 weeks treatment - administered on day 1. Courses repeat every 21 days in the
absence of disease progression or unacceptable toxicity.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Toxicities observed at each dose level utilizing the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
Summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by CTCAE and nadir or maximum values for the laboratory measures), time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize toxicities and side effects by dose and by course.
At least 4 weeks after the start of the first course
Yes
Anthony El-Khoueiry
Principal Investigator
USC/Norris Comprehensive Cancer Center
United States: Food and Drug Administration
0C-11-3
NCT01642342
September 2012
September 2015
Name | Location |
---|---|
USC Norris Comprehensive Cancer Center | Los Angeles, California 90089 |