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DNX-2440 for Resectable Colorectal Liver Metastasis

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ClinicalTrials.gov Identifier: NCT04714983
Recruitment Status : Recruiting
First Posted : January 20, 2021
Last Update Posted : July 15, 2021
Sponsor:
Collaborator:
H. Lee Moffitt Cancer Center and Research Institute
Information provided by (Responsible Party):
DNAtrix, Inc.

Tracking Information
First Submitted Date  ICMJE December 9, 2020
First Posted Date  ICMJE January 20, 2021
Last Update Posted Date July 15, 2021
Actual Study Start Date  ICMJE February 15, 2021
Estimated Primary Completion Date July 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 14, 2021)
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 14, 2021)
  • 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
  • Viral replication [ Time Frame: 3 Years ]
    Viral replication will be assessed by quantitative measurement of viral protein expression by IHC
  • 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).
  • 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.
  • Measure Immune response with ELISPOT [ Time Frame: 3 Years ]
    Immunotherapeutic responses will be assessed by measuring T-cell response (ELISPOT - tissue/blood).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE DNX-2440 for Resectable Colorectal Liver Metastasis
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE Biological: DNX-2440
DNX-2440 is a replication competent oncolytic adenovirus expressing human OX40 ligand.
Study Arms  ICMJE
  • 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.
    Intervention: Biological: DNX-2440
  • 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.
    Intervention: Biological: DNX-2440
  • 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.
    Intervention: Biological: DNX-2440
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 14, 2021)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2023
Estimated Primary Completion Date July 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Nancy Gady, BS 832-930-2401 2440LM-002study@DNAtrix.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04714983
Other Study ID Numbers  ICMJE 2440LM-002
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party DNAtrix, Inc.
Study Sponsor  ICMJE DNAtrix, Inc.
Collaborators  ICMJE H. Lee Moffitt Cancer Center and Research Institute
Investigators  ICMJE
Study Director: Nancy Gady, BS DNAtrix, Inc.
PRS Account DNAtrix, Inc.
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP