Recombinant Albumin Fusion Protein sEphB4-HSA in Treating Patients With Metastatic or Recurrent Solid Tumors
This study is about an experimental drug called sEphB4-HSA (recombinant albumin fusion protein sEphB4-HSA). This research study will be the first time sEphB4-HSA is given to people. sEphB4-HSA prevents tumor cells from multiplying and blocks several compounds that promote the growth of blood vessels that bring nutrients to the tumor. sEphB4-HSA has shrunk colon, lung, breast, glioma, melanoma, prostate and Kaposi's sarcoma tumors in mice
Unspecified Adult Solid Tumor, Protocol Specific
Other: laboratory biomarker analysis
Other: pharmacological study
Biological: recombinant albumin fusion protein sEphB4-HSA
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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).|
- Toxicities observed at each dose level utilizing the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: At least 4 weeks after the start of the first course ] [ Designated as safety issue: Yes ]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.
- Number of patients with complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or inevaluable (IE) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Summarized by dose level in the dose escalation and in the expansion cohort.
- Survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Summarized with Kaplan-Meier plots to describe the outcome.
- Time to failure [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Summarized with Kaplan-Meier plots to describe the outcome.
|Study Start Date:||September 2012|
|Estimated Study Completion Date:||September 2015|
|Estimated Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
Experimental: Treatment (sEphB4-HSA)
Patients receive recombinant albumin fusion protein sEphB4-HSA IV over 60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studiesBiological: recombinant albumin fusion protein sEphB4-HSA
I. To establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of sEphB4-HSA given as an intravenous injection once weekly.
II. To describe the dose limiting toxicities and adverse event profile of sEphB4-HSA when administered as a once weekly injection in patients with advanced solid tumors.
III. To describe the pharmacokinetics of sEphB4-HSA when administered as a once weekly injection.
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 receive recombinant albumin fusion protein sEphB4-HSA intravenously (IV) over 60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|United States, California|
|USC Norris Comprehensive Cancer Center||Recruiting|
|Los Angeles, California, United States, 90033|
|Contact: Jubilee Acap, R.N. 323-865-0593 email@example.com|
|Principal Investigator: Anthony El-Khoueiry|
|Principal Investigator:||Anthony El-Khoueiry||USC/Norris Comprehensive Cancer Center|