DNX-2440 Oncolytic Adenovirus for Recurrent Glioblastoma

NCT03714334 | Terminated Phase 1

• 1 other identifier: D2440GBM1
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with first or second recurrence of GBM will be treated with stereotactic injection of the oncolytic virus DNX-2440.

Conditions

Glioblastoma; Glioblastoma, Adult

Keywords

Recurrent Glioblastoma; oncolytic virus; immunotherapy

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events after brain administration of DNX-2440.

  Incidence and severity of adverse effects will be collected and described

  8 weeks

Secondary Outcomes (3)

• Overall Survival at 12 months (OS12)

  12 months

• Overall survival

  25 months

• Overall response rate (ORR)

  6 months

Study Arms (1)

DNX-2440 injection

EXPERIMENTAL

all the patients included will be treated with the experimental agent

Drug: DNX-2440 injection

Interventions

DNX-2440 injection DRUG

DNX-2440 virus will be injected stereotactically

DNX-2440 injection

Eligibility Criteria

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

You may qualify if:

• Patients willing and able to give informed consent.
• Patient must be, in the investigator opinion, able to comply with all the protocol procedures.
• Age ≥18
• Negative pregnant test in case of fertile women\*
• Patients with diagnosis of first or second recurrence of Glioblastoma or any of its variants (Gliosarcoma, Giant cell Glioblastoma or epithelioid Glioblastoma) based on histopathology at first diagnosis and clinical and radiological follow-up. Recurrences within the radiation field will be considered if there is confirmed growing of the lesion in two MRI, or occur at least 12 weeks after completion of radiotherapy, or if there is clear histopathological confirmation of tumor recurrence. This limitation does not apply for recurrences occurring outside the radiation field
• A single measurable lesion bigger than 10 mm in two perpendicular diameters, considered appropriate for safe stereotactic biopsy and virus injection without entering the ventricle.
• Must have adequate renal, bone marrow and liver function.
• Steroid-free or requiring stable doses of a maximum of 2mg dexamethasone /day or equivalent in the previous two weeks.
• A woman is considered fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.

You may not qualify if:

• Patients with an enhancing lesion bigger than 25cc, including necrotic tumor portions encircled inside the enhancing areas.
• Subjects with immunodeficiency, autoimmune conditions or active hepatitis.
• Any medical or psychological condition that might interfere with the subject's ability to participate or give informed consent or would compromise the patient's ability to tolerate therapy or any disease that will obscure toxicity or dangerously alter drug metabolism.
• Current diagnosis of other cancer except in situ cervical cancer, basal or squamous cell carcinoma of the skin. Patients with a history of another cancer remain eligible if they are cancer free for at least three years.
• Pregnant or breast-feeding females will be excluded, due to the risk for the fetal development of a recombinant virus containing genes related to cellular growth and differentiation.
• Severe bone marrow hypoplasia.
• AST and/or ALT \> 4 times over upper normal laboratory level
• Neutrophils \< 1.5 x 109/L
• Thrombocytes ≤ 100 x 109/L
• Hemoglobin \< 9g/dl
• Multiple lesions, extensive ill-defined diffuse lesions, or lesions considered risky for stereotactic injection of virus, like periventricular lesions.
• Patients with Li-Fraumeni Syndrome or with a known germ line deficit in the retinoblastoma gene or its related pathways.
• Biologic/immunotherapy (e.g., IL-2, IL-12, interferon) within 4 weeks of DNX-2440 administration.
• Vaccination of any kind within 4 weeks prior to DNX-2440 administration.
• Inability to undergo MRI examination for any reason.

Sponsors & Collaborators

• Clinica Universidad de Navarra, Universidad de Navarra: lead
• DNAtrix, Inc.: collaborator

Study Sites (1)

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

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

Study Record Dates

• First Submitted: October 16, 2018
• First Posted: October 22, 2018
• Study Start: October 16, 2018
• Primary Completion: April 5, 2023
• Study Completion: April 5, 2023
• Last Updated: April 7, 2023

Record last verified: 2023-04

Locations

ES (1)