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DNX-2440 for Resectable Colorectal Liver Metastasis

Primary Purpose

Liver Metastases, Liver Metastasis Colon Cancer, Colorectal Cancer

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
DNX-2440
Sponsored by
DNAtrix, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Metastases

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • H. Lee Moffitt Cancer Center and Research Institute, Inc.Recruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Dose-level 1

Dose-level 2

Dose-level 3

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Maximum tolerated dose (MTD) achieved during dose-escalation phase
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).

Secondary Outcome Measures

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

Full Information

First Posted
December 9, 2020
Last Updated
March 28, 2022
Sponsor
DNAtrix, Inc.
Collaborators
H. Lee Moffitt Cancer Center and Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT04714983
Brief Title
DNX-2440 for Resectable Colorectal Liver Metastasis
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 15, 2021 (Actual)
Primary Completion Date
July 31, 2022 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
DNAtrix, Inc.
Collaborators
H. Lee Moffitt Cancer Center and Research Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Metastases, Liver Metastasis Colon Cancer, Colorectal Cancer, Breast Cancer, Gastric Cancer, Periampullary Cancer, Melanoma, Renal Cell Cancer, Sarcoma, Squamous Cell Carcinoma, Gastrointestinal Stromal Tumors

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dose-level 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose-level 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose-level 3
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
DNX-2440
Intervention Description
DNX-2440 is a replication competent oncolytic adenovirus expressing human OX40 ligand.
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD) achieved during dose-escalation phase
Description
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).
Time Frame
1.5 Years
Secondary Outcome Measure Information:
Title
Efficacy of DNX-2440 assessed by Tumor Regression Grade (TRG) score
Description
Efficacy in tumor cell killing will be measured using the TRG score (1-5) for the resected specimens
Time Frame
3 Years
Title
Viral replication
Description
Viral replication will be assessed by quantitative measurement of viral protein expression by IHC
Time Frame
3 Years
Title
Measure Immune response with cell response panels
Description
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).
Time Frame
3 Years
Title
Measure Immune response with ImmunoSEQsec
Description
Immunotherapeutic responses will be assessed by measuring changes in T-cell receptor (TCR) repertoire - tissue and blood.
Time Frame
3 Years
Title
Measure Immune response with ELISPOT
Description
Immunotherapeutic responses will be assessed by measuring T-cell response (ELISPOT - tissue/blood).
Time Frame
3 Years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Joan Robbins, Ph.d
Phone
832-930-2401
Email
2440LM-002study@DNAtrix.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joan Robbins, Ph.d
Organizational Affiliation
DNAtrix, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center and Research Institute, Inc.
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marjorie Brelsford
Phone
813-745-3772
Email
Marjorie.Brelsford@moffitt.org
First Name & Middle Initial & Last Name & Degree
Daniel Anaya, MD
Phone
813-745-1813
Email
Daniel.AnayaSaenz@moffitt.org
First Name & Middle Initial & Last Name & Degree
Daniel Anaya, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

DNX-2440 for Resectable Colorectal Liver Metastasis

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