DNX-2440 for Resectable Colorectal Liver Metastasis

April 5, 2024 updated by: DNAtrix, Inc.

A Phase I Safety and Window-of-opportunity Study of Preoperative Intratumoral Injection of OX40-ligand Expressing Oncolytic Adenovirus (DNX-2440) in Patients With Resectable Liver Metastasis

The purpose of this study is to test an experimental oncolytic adenovirus called DNX-2440 in patients with resectable multifocal (≥ 2 lesions) liver metastasis, who are scheduled to have curative-intent liver resection surgery. Up to 18 patients will receive two sequential intra-tumoral injections of DNX-2440 into a metastatic liver tumor prior to surgery for liver resection, to evaluate safety and biological endpoints across 3 dose levels (dose escalation). Upon conclusion of the dose-escalation phase, the selected safe and biologically appropriate dose will be administered using the same schema for an additional 12 patients with colorectal cancer liver metastasis (expansion cohort) using established biologic endpoints.

Study Overview

Status

Suspended

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center and Research Institute, Inc.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • Male or female aged ≥ 18 years at time of consent
  • Diagnosis of liver metastases from colorectal, breast, gastric, periampullary, melanoma, renal cell cancer, sarcoma, squamous cell carcinoma or gastrointestinal stromal tumor
  • Multiple (≥ 2) liver tumors
  • Candidate for curative-intent surgery
  • Stated willingness to comply with all study procedures and availability for the duration of the study.
  • Candidates eligible for targeted therapy, as per standard of care guidelines (and based on mutational status as indicated), must have completed therapy
  • Preoperative chemotherapy is allowed

Key Exclusion Criteria:

  • Recurrence of liver metastasis
  • Diagnosis of neuroendocrine tumor liver metastasis
  • Liver metastasis treated with > 12 cycles of systemic chemotherapy
  • Condition that requires ongoing systemic immunosuppressive therapy
  • Evidence of inadequate organ function based on lab parameters
  • Liver transaminases (aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT]) or total bilirubin > 5x the upper limits of normal
  • Males or females who refuse to use a double-barrier form of birth control during the study and for up to 6 months after injection with DNX-2440

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose-level 1
The dose-level 1 arm will use a 3+3 design. A single dose of DNX-2440 will be delivered via intra-tumoral injection at Visit 1 and at Visit 3 (2 administrations in total) approximately 14 days apart.
Biological: DNX-2440
DNX-2440 is a replication competent oncolytic adenovirus expressing human OX40 ligand.
Experimental: Dose-level 2
The dose-level 2 arm will use a 3+3 design. A single dose of DNX-2440 will be delivered via intra-tumoral injection at Visit 1 and at Visit 3 (2 administrations in total) approximately 14 days apart.
Biological: DNX-2440
DNX-2440 is a replication competent oncolytic adenovirus expressing human OX40 ligand.
Experimental: Dose-level 3
The dose-level 3 arm will use a 3+3 design. A single dose of DNX-2440 will be delivered via intra-tumoral injection at Visit 1 and at Visit 3 (2 administrations in total) approximately 14 days apart.
Biological: DNX-2440
DNX-2440 is a replication competent oncolytic adenovirus expressing human OX40 ligand.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose (MTD) achieved during dose-escalation phase
Time Frame: 1.5 Years
The MTD will be defined as the highest tolerated dose below the dose that results in greater than or equal to one-third of the subjects exposed who experience a dose-limiting toxicity (DLT).
1.5 Years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of DNX-2440 assessed by Tumor Regression Grade (TRG) score
Time Frame: 3 Years
Efficacy in tumor cell killing will be measured using the TRG score (1-5) for the resected specimens
3 Years
Viral replication
Time Frame: 3 Years
Viral replication will be assessed by quantitative measurement of viral protein expression by IHC
3 Years
Measure Immune response with cell response panels
Time Frame: 3 Years
Immunotherapeutic responses will be assessed by examining features and measuring changes following the intervention for Immunologic microenvironment (T-cell and Myeloid-cell response panels-tissue).
3 Years
Measure Immune response with ImmunoSEQsec
Time Frame: 3 Years
Immunotherapeutic responses will be assessed by measuring changes in T-cell receptor (TCR) repertoire - tissue and blood.
3 Years
Measure Immune response with ELISPOT
Time Frame: 3 Years
Immunotherapeutic responses will be assessed by measuring T-cell response (ELISPOT - tissue/blood).
3 Years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

DNAtrix, Inc.

Collaborators

H. Lee Moffitt Cancer Center and Research Institute

Investigators

  • Study Director: Joan Robbins, Ph.d, DNAtrix, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 15, 2021

Primary Completion (Estimated)

July 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

December 9, 2020

First Submitted That Met QC Criteria

January 14, 2021

First Posted (Actual)

January 20, 2021

Study Record Updates

Last Update Posted (Actual)

April 9, 2024

Last Update Submitted That Met QC Criteria

April 5, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2440LM-002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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