Entolimod in Treating Patients With Locally Advanced or Metastatic Solid Tumors That Cannot Be Removed By Surgery

NCT01527136 | Completed Phase 1 DMC

• 2 other identifiers: I 196111NCI-2011-03565
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of entolimod in treating patients with locally advanced or metastatic solid tumors that cannot be removed by surgery. Biological therapies, such as entolimod, may stimulate the immune system in different ways and stop tumor cells from growing.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (2)

• MTD of entolimod

  Evaluated using National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.

  3 weeks

• Safety of entolimod

  Evaluated using NCI-CTCAE Version 4.0.

  Up to 30 days post-treatment

Secondary Outcomes (3)

• Efficacy of entolimod in patients with advanced cancers in terms of objective response rate (ORR) and RECIST response

  Up to 3 months

• PK profiles of entolimod in patients with advanced cancers

  Pre-dose, 2, 4, 6, 8, 24 hours, post dose for, days 1, 4, 8 and 11

• PD profiles of entolimod in patients with advanced cancers

  PD plasma: pre-dose, at 2, 4 and 6 hours post dose on day 1, 4, 8, 11, 15, 22, and 43

Study Arms (1)

Treatment (entolimod)

EXPERIMENTAL

Patients receive entolimod IM or SC on days 1, 4, 8, and 11. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.

Drug: entolimod; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

entolimod DRUG

Given IM or SC

Also known as: CBLB502, TLR5 agonist CBLB502, toll-like receptor 5 agonist CBLB502

Treatment (entolimod)

pharmacological study OTHER

Correlative studies

Treatment (entolimod)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (entolimod)

Eligibility Criteria

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

You may qualify if:

• Written informed consent granted prior to initiation of any study-specific screening procedures, given with the understanding that the patient has the right to withdraw from the study at any time, without prejudice
• Histologically or cytologically confirmed locally advanced, inoperable or metastatic solid tumor for which no acceptable therapy exists
• Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Life expectancy greater than 3 months
• Platelet count \>= 75 x 10\^9/L
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
• Hemoglobin (Hgb) \>= 9 gm/dL
• Total bilirubin =\< 1.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN, regardless of the presence of liver metastases
• Creatinine =\< 2 x ULN
• Left ventricular ejection fraction (LVEF) \>=45% by echocardiogram (ECHO) or multi gated acquisition scan (MUGA)
• Lead Electrocardiogram (ECG) with normal tracing or non-clinically significant changes that do not require medical intervention
• QTcB interval \< 470 msec at any point prior to receiving the first dose of study drug (mean of replicate values, correction per institutional standard) and no history of Torsades des Pointes or other symptomatic QTcB abnormality
• Absence of orthostatic hypotension

You may not qualify if:

• Male and female subjects of child-bearing potential who do not agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after last investigational drug dose received
• Previous anti-cancer chemotherapy, immunotherapy or investigational agents =\< 3 weeks prior to the first day of study defined treatment; palliative radiation \< 2 weeks; patients who receive gamma knife radiosurgery for brain metastases are eligible if procedure was performed \> 2 weeks before treated is started, is clinically stable and is not receiving corticosteroid therapy; ongoing hormonal therapies (such as, luteinizing hormone-releasing hormone \[LHRH\] antagonists, megestrol, anti-estrogens, or aromatase inhibitors) are allowed
• Previous treatment with a TLR5 agonist
• Patients with a known hypersensitivity to CBLB502 or to its excipients
• Presence of neutralizing antibodies to CBLB502
• Patient has a history of cardiac dysfunction including any of the following:
• Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes; patients with persistent regional wall abnormalities on assessment of LVEF function are not eligible
• History of documents congestive heart failure (New York Heart Association \[NYHA\] functional classification III-IV) within 6 months
• Documented cardiomyopathy
• Diagnosed or suspected congenital QT syndrome
• Any history of second or third degree heart block (may be eligible if currently have a pacemaker)
• Heart rate \< 50 beats/minute on pre-entry electrocardiogram
• Uncontrolled hypertension defined as systolic blood pressure \> 160 mm Hg on 3 consecutive measurements prior to study enrollment
• Active clinically serious infections defined as \>= Grade 2 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
• Substance abuse, medical, psychological, or social conditions that may, in the opinion of the Investigator, interfere with the patient's participation in the study or evaluation of the study results

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• Cleveland BioLabs, Inc.: collaborator

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Interventions

CBLB502

Study Officials

• Alex Adjei

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2011
• First Posted: February 6, 2012
• Study Start: January 1, 2012
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: July 22, 2022

Record last verified: 2022-07

Locations

US (1)