Clinical trial NCT04714983: 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
Overall status: SUSPENDED
Phase: PHASE1
Conditions: 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
Lead sponsor: DNAtrix, Inc.
Sponsor class: INDUSTRY
Collaborators: name: H. Lee Moffitt Cancer Center and Research Institute
First posted: 2021-01-20
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Maximum tolerated dose (MTD) achieved during dose-escalation phase
timeFrame: 1.5 Years
Secondary outcomes:
measure: Efficacy of DNX-2440 assessed by Tumor Regression Grade (TRG) score
timeFrame: 3 Years
measure: Viral replication
timeFrame: 3 Years
measure: Measure Immune response with cell response panels
timeFrame: 3 Years
measure: Measure Immune response with ImmunoSEQsec
timeFrame: 3 Years
measure: Measure Immune response with ELISPOT
timeFrame: 3 Years
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute, Inc.
state: Florida
Study officials:
affiliation: DNAtrix, Inc.
name: Joan Robbins, Ph.d
role: STUDY_DIRECTOR
References: