DNX-2440 for Resectable Colorectal Liver Metastasis

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT04714983
• Other study ID #: 2440LM-002
• Status: Suspended
• Phase: Phase 1
• Start date: February 15, 2021
• Est. completion date: December 31, 2026

Study information

• Verified date: April 2024
• Source: DNAtrix, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 30
• Est. completion date: December 31, 2026
• Est. primary completion date: July 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Carcinoma, Renal Cell
• Colorectal Cancer
• Gastric Cancer
• Gastrointestinal Stromal Tumors
• Liver Metastases
• Liver Metastasis Colon Cancer
• Liver Neoplasms
• Melanoma
• Neoplasm Metastasis
• Neoplasms, Second Primary
• Periampullary Cancer
• Renal Cell Cancer
• Sarcoma
• Squamous Cell Carcinoma

Intervention

Biological:
• DNX-2440
DNX-2440 is a replication competent oncolytic adenovirus expressing human OX40 ligand.

Locations

Country	Name	City	State
United States	H. Lee Moffitt Cancer Center and Research Institute, Inc.	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
DNAtrix, Inc.	H. Lee Moffitt Cancer Center and Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	1.5 Years
Secondary	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	3 Years
Secondary	Viral replication	Viral replication will be assessed by quantitative measurement of viral protein expression by IHC	3 Years
Secondary	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).	3 Years
Secondary	Measure Immune response with ImmunoSEQsec	Immunotherapeutic responses will be assessed by measuring changes in T-cell receptor (TCR) repertoire - tissue and blood.	3 Years
Secondary	Measure Immune response with ELISPOT	Immunotherapeutic responses will be assessed by measuring T-cell response (ELISPOT - tissue/blood).	3 Years