Recombinant Albumin Fusion Protein sEphB4-HSA in Treating Patients With Metastatic or Recurrent Solid Tumors

NCT01642342 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: 0C-11-3NCI-2012-00971
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (4)

• 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

• Number of patients with complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or inevaluable (IE)

  Summarized by dose level in the dose escalation and in the expansion cohort.

  Up to 2 years

• Survival

  Summarized with Kaplan-Meier plots to describe the outcome.

  Up to 2 years

• Time to failure

  Summarized with Kaplan-Meier plots to describe the outcome.

  Up to 2 years

Study Arms (3)

Weekly Treatment (sEphB4-HSA)

EXPERIMENTAL

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; Other: pharmacological study; Biological: recombinant albumin fusion protein sEphB4-HSA

Every 2 Weeks Treatment (sEphB4-HSA)

EXPERIMENTAL

Patients receive recombinant EphB4-HSA fusion protein IV over 60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: laboratory biomarker analysis; Other: pharmacological study; Biological: recombinant albumin fusion protein sEphB4-HSA

Every 3 Weeks Treatment (sEphB4-HSA)

EXPERIMENTAL

Patients receive recombinant EphB4-HSA fusion protein IV over 60 minutes on days 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Other: laboratory biomarker analysis; Other: pharmacological study; Biological: recombinant albumin fusion protein sEphB4-HSA

Interventions

laboratory biomarker analysis OTHER

Correlative studies

Every 2 Weeks Treatment (sEphB4-HSA); Every 3 Weeks Treatment (sEphB4-HSA); Weekly Treatment (sEphB4-HSA)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Every 2 Weeks Treatment (sEphB4-HSA); Every 3 Weeks Treatment (sEphB4-HSA); Weekly Treatment (sEphB4-HSA)

recombinant albumin fusion protein sEphB4-HSA BIOLOGICAL

Given IV

Every 2 Weeks Treatment (sEphB4-HSA); Every 3 Weeks Treatment (sEphB4-HSA); Weekly Treatment (sEphB4-HSA)

Eligibility Criteria

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

You may qualify if:

• For expansion Cohort A: Advanced (metastatic or recurrent) pathologically proven solid tumor which has not responded to standard therapy or which has progressed following standard therapy for advanced disease and/or for which no standard therapy is known to be effective. Measurable disease required.
• For expansion Cohort B: Advanced pathologically proven mutant KRAS non-small cell lung cancer (group 1), pancreatic cancer (group 2; documentation of KRAS mutation not required), mutant KRAS colorectal cancer (group 3), head and neck squamous cell carcinoma (group 4) mesothelioma (group 5), hepatocellular cancer (group 6), and biliary carcinoma (group 7). Measurable disease required.
• Must agree, as part of the informed consent, to provide blood and tumor samples for molecular correlates, pharmacokinetics and pharmacodynamics. Patients in expansion cohort A must have tumor sites that are accessible for tumor biopsy and must agree to undergo a pre-treatment and post-treatment biopsy. Patients in cohort B group 3 \& 4 must have tumor sites that are accessible for tumor biopsy and must agree to undergo a pre-treatment and post-treatment biopsy.
• Must have an Eastern Cooperative Oncology Group (ECOG) performance score of 0-1
• Life expectancy of at least 12 weeks
• Patients or their legal representatives must be able to comprehend and provide written informed consent
• White blood count (WBC) \>= 3,000/μl
• Absolute neutrophil count (ANC) \>= 1,500/μl
• Platelet count \>= 100,000/μl (except in hepatocellular carcinoma patients with portal hypertension for whom a platelet count of \>= 70,000/μl is allowed)
• Serum creatinine =\< 1.5 X upper limit of normal (ULN) for reference lab
• Creatinine Clearance of \>= 60 (as calculated by Cockcroft-Gault formula
• Serum bilirubin =\< 1.5 mg/dL
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels =\< 3X the ULN for the reference lab (=\< 5X the ULN if there is evidence of hepatic involvement by malignant disease)
• Recovered to grade 1 from the effects (excluding alopecia) of any prior therapy for their malignancies
• 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

You may not qualify if:

• Undergoing or have undergone in the past 28 days any other therapy for their cancer, including radiation and adjuvant therapy
• Major systemic infection requiring antibiotics 72 hours or less prior to first dose of study drug
• 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 in the dose escalation portion of the trial
• Have New York Heart Association (NYHA) class 3 or 4, myocardial infarction, 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 contraindicates treatment with sEphB4HSA or places the patient at undue risk for treatment related complications
• 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
• Pregnant or lactating
• On any dose of warfarin or are on full dose anticoagulation with other agents, including low molecular weight heparin, antithrombin agents, antiplatelet 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
• Any active bleeding in the last =\< 4 weeks or have an otherwise known bleeding diathesis
• QTcF (Fridericia Correction Formula) \> 480 on 2 out of 3 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)
• For cohort B, group 1: Non-small cell lung cancer:
• Must not have clinically significant active hemoptysis
• For cohort B, group 4: Head and neck squamous cell cancer:
• Must not have evidence of major vessel involvement or encasement by tumor
• For cohort B, group 6: Hepatocellular Carcinoma:
• Child Pugh score \> 7

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator
• Vasgene Therapeutics, Inc: collaborator
• The V Foundation for Cancer Research: collaborator

Study Sites (1)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

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 14, 2012
• First Posted: July 17, 2012
• Study Start: September 6, 2012
• Primary Completion: May 29, 2019
• Study Completion: May 29, 2019
• Last Updated: August 24, 2022

Record last verified: 2022-08

Locations

US (1)