DNX-2401 (Formerly Known as Delta-24-RGD-4C) for Recurrent Malignant Gliomas

NCT00805376 | Completed Phase 1

• 1 other identifier: ID01-310
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find the highest tolerable dose of DNX-2401 that can be injected directly into brain tumors and into the surrounding brain tissue where tumor cells can multiply. A second goal is to study how the new drug DNX-2401 affects brain tumor cells and the body in general.

Conditions

Brain Cancer; Central Nervous System Diseases

Keywords

Brain; Brain Cancer; Central Nervous System Diseases; CNS; Conditionally Replication-Competent Adenovirus; Delta-24-RGD; DNX-2401; Recurrent Malignant Gliomas; malignant brain tumor

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) DNX-2401

  Each cohort of three subjects each sequentially assigned to escalating doses of DNX-2401, with acceptable grade of neurotoxicity Common Toxicity Criteria (CTC) \< grade 3, related to the study drug, and according to standard Gehan phase I dose-escalating criteria for toxicity.

  Assessed during 14 day waiting period between doses (every 28 days).

Study Arms (2)

Group A: DNX-2401

EXPERIMENTAL

Surgical procedure precisely injects DNX-2401 through a catheter (small tube) into brain tumor.

Drug: DNX-2401

Group B: DNX-2401 + Surgery

EXPERIMENTAL

DNX-2401 injection + Tumor removal

Drug: DNX-2401; Procedure: Tumor Removal

Interventions

DNX-2401 DRUG

Surgical procedure precisely injects DNX-2401 through a catheter (small tube) into brain tumor.

Also known as: Delta-24-RGD-4C

Group A: DNX-2401; Group B: DNX-2401 + Surgery

Tumor Removal PROCEDURE

Surgical Tumor Resection

Also known as: Craniotomy

Group B: DNX-2401 + Surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically proven recurrent malignant primary glioma will be eligible. Glioma type will be restricted to: GBM, gliosarcoma (GS), anaplastic gliomas \[anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic infiltrating glioma (AIG), mixed anaplastic glioma (MAG), anaplastic ependymoma\]
• Patients must show unequivocal evidence for tumor recurrence or progression by MRI scan within 15 days prior to Day 0/Baseline procedure after failing prior surgical resection, biopsy, chemotherapy or radiation
• For patients entered in Group A (see Treatment Plan) tumors must be accessible for stereotactic injection. Tumors must be between 1.0 - 5.0 cm in diameter
• For patients entered in Group B (see Treatment Plan) tumors must be surgically resectable, and surgical resection must be indicated at the time of baseline evaluation. Tumors must be \>1.0 cm in diameter.
• Patients will consent to have a biopsy taken at the time of the stereotactic injection to confirm the presence of malignant glioma (based on frozen section) before injection of DNX-2401
• For each patient there must be a consensus between the physician investigators in this study that injection will not deliver DNX-2401 into the ventricular system. Patients must have a stable steroid regimen for at least 1 week prior to DNX-2401 administration
• Patients may or may not have had prior chemotherapy
• Patients must be willing and able to give informed consent
• Age \> /= 18 years
• Patients must have a Karnofsky performance status greater than or equal to 70
• Patients must have recovered from the toxic effects of prior therapy (i.e., CTC grade 1 or less). For example, they must be at least two weeks after vincristine, 6 weeks after nitrosoureas, and 3 weeks after procarbazine or temozolomide administration
• Patients must have adequate bone marrow function (absolute granulocyte count \> 1,500 and platelet count of \> 100,000), adequate liver function (SGPT and alkaline phosphatase \< 2 times institutional normals and bilirubin \<1.5 mg%), and adequate renal function (BUN or creatinine \<1.5 times institutional normal) prior to starting therapy
• This study was designed to include women and minorities, but was not designed to measure differences of intervention effects. Males and females will be recruited with no preference to gender

You may not qualify if:

• Any radiotherapy within 4 weeks prior to date of DNX-2401 administration.
• Active uncontrolled infection or severe intercurrent medical conditions. All patients must be afebrile at baseline (i.e., \< 38.0 Celsius \[C\])
• Evidence of bleeding diathesis or use of anticoagulant medication or any medication that may increase the risk of bleeding that cannot be stopped prior to surgery. If the medication can be discontinued , based on the clinical judgment of the surgeon, prior to DNX-2401 injection then patient may be eligible.
• History or current diagnosis of any medical or psychological condition that in the Investigator's opinion, might interfere with the subject's ability to participate or inability to obtain informed consent because of psychiatric or complicating medical problems
• Female who is pregnant and/or nursing. Because of the potential risk of a recombinant virus containing a gene involved in cellular growth regulation and differentiation which could potentially affect a developing fetus or growing infant, females who are pregnant, at risk of pregnancy, or breast feeding a baby during the study period are excluded
• Tumor position that, in the Investigator's opinion, would pose the risk of penetration of the cerebral ventricular system during injection with study drug. If, during the DNX-2401injection procedure, penetration of the ventricular system is suspected or confirmed, DNX-2401 administration will be aborted
• Immunocompromised subjects, subjects with autoimmune conditions, active hepatitis (B or C) or HIV seropositivity
• Patients with Li-Fraumeni Syndrome or with a known germ line deficit in the retinoblastoma gene or its related pathways
• Multiple intracranial malignant glioma lesions at the time of recurrence. Multiple enhancing areas within a single tumor will not be considered multiple glioma lesions
• Tumor involvement which would require ventricular, brainstem or posterior fossa injection or access through a ventricle in order to deliver the virus
• Tumor involving the subependyma or suspected cerebrospinal fluid (CSF) dissemination
• Documented extracranial metastasis
• Biologic/immunotherapy (e.g., IL-2, IL-12, interferon) within 4 weeks of DNX-2401 administration
• Concurrent chemotherapy, radiation or biological therapy
• Any contraindication for undergoing MRI such as: individuals with pacemakers, epicardial pacer wires, infusion pumps, surgical and/or aneurysm clips, shrapnel, metal prosthesis, implants with potential magnetic properties, metallic bodies in the eyes, etc.

Sponsors & Collaborators

• DNAtrix, Inc.: lead

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Lang FF, Conrad C, Gomez-Manzano C, Yung WKA, Sawaya R, Weinberg JS, Prabhu SS, Rao G, Fuller GN, Aldape KD, Gumin J, Vence LM, Wistuba I, Rodriguez-Canales J, Villalobos PA, Dirven CMF, Tejada S, Valle RD, Alonso MM, Ewald B, Peterkin JJ, Tufaro F, Fueyo J. Phase I Study of DNX-2401 (Delta-24-RGD) Oncolytic Adenovirus: Replication and Immunotherapeutic Effects in Recurrent Malignant Glioma. J Clin Oncol. 2018 May 10;36(14):1419-1427. doi: 10.1200/JCO.2017.75.8219. Epub 2018 Feb 12.

  PMID: 29432077 DERIVED

MeSH Terms

Conditions

Brain Neoplasms; Central Nervous System Diseases; Glioma

Interventions

Craniotomy

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Nervous System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Neurosurgical Procedures; Surgical Procedures, Operative

Study Officials

• Frederick F. Lang, MD, BS

  UT MD Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2008
• First Posted: December 9, 2008
• Study Start: February 1, 2009
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: July 16, 2018

Record last verified: 2018-01

Locations

US (1)