Recombinant EphB4-HSA Fusion Protein With Standard Chemotherapy Regimens in Treating Patients With Advanced or Metastatic Solid Tumors

PRIMARY OBJECTIVES:

I. To document the safety and tolerability of sEphB4-HSA (recombinant ephB4-HSA fusion protein) intravenously (IV) weekly when administered in combination with: arm A) gemcitabine (gemcitabine hydrochloride) and nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation), arm B) docetaxel, arm C) gemcitabine and cisplatin.

SECONDARY OBJECTIVES:

I. To describe the adverse event profile of sEphB4-HSA IV weekly when administered in combination with: arm A) gemcitabine and nab-paclitaxel, arm B) docetaxel, arm C) gemcitabine and cisplatin.

II. To characterize the pharmacokinetics of sEphB4-HSA when combined with: arm A) gemcitabine and nab-paclitaxel, arm B) docetaxel, arm C) gemcitabine and cisplatin.

III. To assess, in a preliminary fashion, the anti-tumor efficacy of sEphB4-HSA in combination with the various chemotherapy regimens in each of the 4 cohorts separately: Arm A cohort 1-patients with advanced pancreatic cancer; Arm B cohort 2-patients with head and neck cancer; Arm B cohort 3-patients with non-small cell lung cancer; Arm C cohort 3: patients with cholangiocarcinoma.

TERTIARY OBJECTIVES:

I. To evaluate the expression of EPH receptor B4 (EphB4) and ephrinB2 in the archival tumor samples and explore potential associations with outcome.

II. To bank specimens for future correlative biomarkers studies based on the results of ongoing biomarkers analyses in the phase I of sEphB4-HSA as a single agent.

OUTLINE: This is a dose de-escalation study of recombinant EphB4-HSA fusion protein. Patients are assigned to 1 of 3 treatment arms.

ARM A: Patients receive recombinant EphB4-HSA fusion protein IV over 1 hour on days 1, 8, 15, and 22 (beginning course 2), paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive recombinant EphB4-HSA fusion protein IV over 1 hour on days 1, 8, and 15 (beginning course 2) and docetaxel IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.