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

NCT02495896 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 0S-15-5NCI-2015-00987P30CA014089
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 2

Brief 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.

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 Pancreatic Cancer; Unresectable Gallbladder Carcinoma; Unresectable Pancreatic Cancer; Stage IV Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (5)

• Duration of overall response or SD

  From first occurrence of CR, PR or SD to the time of documented disease progression, as determined by investigator review of tumor assessments using RECIST v1.1, or death from any cause, assessed up to 2 years

• Incidence of toxicities, graded according to Common Terminology Criteria for Adverse Events version 4

  Up to 2 years

• Objective response using RECIST version 1.1

  Patients whose best overall response is CR or PR will be classified as having a major objective response.

  Up to 2 years

• Overall survival

  Time from start of treatment with recombinant EphB4-HSA fusion protein (start of 2nd course) to death for any cause, assessed up to 2 years

• Progression-free survival

  Time from start of treatment to 1st documentation of PD or death due to any cause, or death from any cause, assessed up to 2 years

Study Arms (3)

Arm A (sEphB4-HSA, nab-paclitaxel, gemcitabine hydrochloride)

EXPERIMENTAL

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.

Drug: Gemcitabine Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel Albumin-Stabilized Nanoparticle Formulation; Other: Pharmacological Study; Biological: Recombinant EphB4-HSA Fusion Protein

Arm B (sEphB4-HSA, docetaxel)

EXPERIMENTAL

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.

Drug: Docetaxel; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: Recombinant EphB4-HSA Fusion Protein

Arm C (sEphB4-HSA, cisplatin, gemcitabine hydrochloride)

EXPERIMENTAL

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.

Drug: Cisplatin; Drug: Gemcitabine Hydrochloride; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: Recombinant EphB4-HSA Fusion Protein

Interventions

Cisplatin DRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Arm C (sEphB4-HSA, cisplatin, gemcitabine hydrochloride)

Docetaxel DRUG

Given IV

Also known as: RP56976, Taxotere, Taxotere Injection Concentrate

Arm B (sEphB4-HSA, docetaxel)

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar, LY-188011

Arm A (sEphB4-HSA, nab-paclitaxel, gemcitabine hydrochloride); Arm C (sEphB4-HSA, cisplatin, gemcitabine hydrochloride)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm A (sEphB4-HSA, nab-paclitaxel, gemcitabine hydrochloride); Arm B (sEphB4-HSA, docetaxel); Arm C (sEphB4-HSA, cisplatin, gemcitabine hydrochloride)

Paclitaxel Albumin-Stabilized Nanoparticle Formulation DRUG

Given IV

Also known as: ABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel, Albumin-Stabilized Nanoparticle Paclitaxel, nab-paclitaxel, Nanoparticle Albumin-bound Paclitaxel, Nanoparticle Paclitaxel, protein-bound paclitaxel

Arm A (sEphB4-HSA, nab-paclitaxel, gemcitabine hydrochloride)

Pharmacological Study OTHER

Correlative studies

Arm A (sEphB4-HSA, nab-paclitaxel, gemcitabine hydrochloride); Arm B (sEphB4-HSA, docetaxel); Arm C (sEphB4-HSA, cisplatin, gemcitabine hydrochloride)

Recombinant EphB4-HSA Fusion Protein BIOLOGICAL

Given IV

Also known as: sEphB4-HSA

Arm A (sEphB4-HSA, nab-paclitaxel, gemcitabine hydrochloride); Arm B (sEphB4-HSA, docetaxel); Arm C (sEphB4-HSA, cisplatin, gemcitabine hydrochloride)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
• Patients must have a life expectancy of at least 12 weeks
• Patients must be able to comprehend and provide written informed consent
• Women of childbearing potential (WOCBP) and male patients with WOCBP partner must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of investigational product in such a manner that the risk of pregnancy is minimized; WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal; post menopause is defined as:
• Amenorrhea \>= 12 consecutive months without another cause or
• For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level \> 35 mIU/mL
• Women who are using oral contraceptives, other hormonal contraceptives (vagina products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (e.g., vasectomy) should be considered to be of childbearing potential
• WOCBP must have a negative serum test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 72 hours prior to the start of investigational product
• Patients with hepatitis B infection must be on appropriate antiviral therapy
• ARM A COHORT 1: Patients must have advanced pancreatic adenocarcinoma (unresectable or metastatic)
• ARM A COHORT 1: Patients must not have received prior therapy for metastatic or advanced disease; adjuvant therapy that is gemcitabine based is allowed as long as the adjuvant treatment was completed \>= 6 months before the diagnosis of recurrent disease
• ARM A COHORT 1: Absolute neutrophil count \>= 1,500/ul
• ARM A COHORT 1: Platelet count \>= 100,000/ul
• ARM A COHORT 1: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2 x upper limit of normal (ULN); if liver metastases are present then must be \< 5 X the ULN

You may not qualify if:

• Patients must not have received any anti-cancer therapy (cytotoxic chemotherapy, targeted therapy or radiation) within the past 28 days prior to initiation of study therapy
• Patients must not have an active major systemic infection requiring systemic antibiotics 72 hours or less prior to the first dose of study drug
• Patients must not have untreated central nervous system (CNS) metastases; patients whose CNS metastases have been treated by surgery or radiotherapy, who are no longer on corticosteroids, and who are neurologically stable may be enrolled
• Patients must not have any of the following: New York Heart Association (NYHA) class 3 or 4 congestive heart failure; myocardial infarction within the past 12 months, acute coronary syndrome, diabetes mellitus with ketoacidosis or chronic obstructive pulmonary disease (COPD) requiring hospitalization in the preceding 6 months; or any other intercurrent medical condition that contra-indicates treatment with sEphB4HSA or places the patient at undue risk for treatment related complications
• Patients must not have any other condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results
• Patients must not be pregnant of lactating
• Patients must not be on any dose of warfarin or are on full dose anticoagulation with other agents, including low molecular weight heparin, antithrombin agents, anti-platelet agents and full dose aspirin within 7 days prior to first dose of study drug; patients on prophylactic doses of low-molecular weight heparin are allowed
• Patients must not have had any active bleeding in the last =\< 4 weeks or have an otherwise known bleeding diathesis
• Patients must not have corrected QT (QTc)F (Fridericia Correction Formula) \> 480 on 2 out of 3 electrocardiograms (EKG's) (if first EKG is =\< 480, no need to repeat, if first EKG is \> 480 repeat twice for a total of 3 EKG's)
• Patients must not have uncontrolled hypertension as defined by systolic blood pressure (SBP) \>= 160 mmHg or diastolic blood pressure (DBP) \>= 90 mmHg; patients whose blood pressure can be controlled medically are allowed to be rescreened once blood pressure (BP) is under control
• Patients must not have \> grade sensory neuropathy
• Patients must not have known human immunodeficiency virus (HIV) infection
• ARM A COHORT 1: Patients must not have prior nab-paclitaxel exposure
• ARM A COHORT 1: Patients must not have a history of slowly progressive dyspnea and unproductive cough, or of conditions such as sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis, or multiple allergies
• ARM B COHORT 2: Patients must not have prior exposure to docetaxel

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• Vasgene Therapeutics, Inc: collaborator
• University of Southern California: lead

Study Sites (2)

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Gallbladder Neoplasms; Carcinoma, Non-Small-Cell Lung; Pancreatic Neoplasms

Interventions

Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Docetaxel; Gemcitabine; Taxes; Albumin-Bound Paclitaxel; 130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Biliary Tract Neoplasms; Digestive System Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Gallbladder Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Economics; Health Care Economics and Organizations; Paclitaxel; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Anthony El-Khoueiry

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2015
• First Posted: July 13, 2015
• Study Start: September 3, 2015
• Primary Completion: April 1, 2021
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 29, 2026

Record last verified: 2026-04

Locations

US (2)