NCT02495896

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

A Pilot Multi-arm Study of sEphB4-HSA in Combination With Different Chemotherapy Regimens in Patients With Specific Advanced or Metastatic Solid Tumors

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 61 (actual)
• Sponsor: University of Southern California · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This pilot phase Ib trial studies the side effects and best dose of recombinant EphB4-HSA fusion protein when given together with standard chemotherapy regimens in treating patients with solid tumors that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced) or have spread to other places in the body (metastatic). Drugs used in chemotherapy, such as recombinant EphB4-HSA fusion protein, paclitaxel albumin-stabilized nanoparticle formulation, gemcitabine hydrochloride, docetaxel, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether standard chemotherapy regimens are more effective with recombinant ephB4-HSA fusion protein in treating advanced or metastatic solid tumors.

Detailed description

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. ARM C: Patients receive recombinant EphB4-HSA fusion protein IV over 1 hour on days 1, 8, and 15 (beginning course 2), cisplatin IV over 120 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. In all arms, patients with chemotherapy related toxicity may continue treatment with recombinant EphB4-HSA fusion protein alone. Patients with toxicity related to recombinant EphB4-HSA fusion protein may continue treatment with chemotherapy at the discretion of the investigator. After completion of study treatment, patients are followed up periodically.

Conditions

• Head and Neck Squamous Cell Carcinoma
• Metastatic Pancreatic Adenocarcinoma
• Non-Resectable Cholangiocarcinoma
• Pancreatic Adenocarcinoma
• Recurrent Gallbladder Carcinoma
• Recurrent Non-Small Cell Lung Carcinoma
• Stage III Pancreatic Cancer
• Stage IIIA Gallbladder Cancer
• Stage IIIA Non-Small Cell Lung Cancer
• Stage IIIB Gallbladder Cancer
• Stage IIIB Non-Small Cell Lung Cancer
• Stage IV Gallbladder Cancer
• Stage IV Non-Small Cell Lung Cancer
• Stage IV Pancreatic Cancer
• Unresectable Gallbladder Carcinoma
• Unresectable Pancreatic Cancer

Interventions

Type	Name	Description
DRUG	Cisplatin	Given IV
DRUG	Docetaxel	Given IV
DRUG	Gemcitabine Hydrochloride	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Paclitaxel Albumin-Stabilized Nanoparticle Formulation	Given IV
OTHER	Pharmacological Study	Correlative studies
BIOLOGICAL	Recombinant EphB4-HSA Fusion Protein	Given IV

Timeline

• Start date: 2015-09-03
• Primary completion: 2021-04-01
• Completion: 2026-04-01
• First posted: 2015-07-13
• Last updated: 2025-11-10

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study