DNX-2440 Oncolytic Adenovirus for Recurrent Glioblastoma

• ClinicalTrials.gov Identifier: NCT03714334
• Recruitment Status: Terminated
• First Posted: October 22, 2018
• Last Update Posted: April 7, 2023
• Sponsor: Clinica Universidad de Navarra, Universidad de Navarra
• Collaborator: DNAtrix, Inc.
• Information provided by (Responsible Party): Clinica Universidad de Navarra, Universidad de Navarra

Tracking Information

• First Submitted Date: October 16, 2018
• First Posted Date: October 22, 2018
• Last Update Posted Date: April 7, 2023
• Actual Study Start Date: October 16, 2018
• Actual Primary Completion Date: April 5, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 19, 2018)

Incidence of Treatment-Emergent Adverse Events after brain administration of DNX-2440. [ Time Frame: 8 weeks ]

Incidence and severity of adverse effects will be collected and described

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 19, 2018)

• Overall Survival at 12 months (OS12) [ Time Frame: 12 months ]
  rate of patients surviving at 12 months since injection
• Overall survival [ Time Frame: 25 months ]
  Survival along the whole interval of follow-up
• Overall response rate (ORR) [ Time Frame: 6 months ]
  total of patients with Complete responses plus partial responses

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: DNX-2440 Oncolytic Adenovirus for Recurrent Glioblastoma
• Official Title: Phase I Trial of DNX-2440 Oncolytic Adenovirus in Patients With Recurrent Glioblastoma
• Brief Summary: Patients with first or second recurrence of GBM will be treated with stereotactic injection of the oncolytic virus DNX-2440.

Detailed Description

After inclusion in the trial, stereotactic biopsy will be performed. In the same surgery, the experimental agent will be injected also by stereotactic system, in a different part of the lesion, in a region considered viable tumor, using a cannula especially designed for virus injection.

Follow-up will include clinical visits and MRI No other treatment for the tumor will be used until progression is documented. iRANO criteria and volumetric measurement of the tumor will be used.

Any further treatment after progression will be at the criteria of the treating physician

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Glioblastoma
• Glioblastoma, Adult

Intervention

Drug: DNX-2440 injection

DNX-2440 virus will be injected stereotactically

Study Arms

Experimental: DNX-2440 injection

all the patients included will be treated with the experimental agent

Intervention: Drug: DNX-2440 injection

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: April 5, 2023): 16
• Original Estimated Enrollment (submitted: October 19, 2018): 24
• Actual Study Completion Date: April 5, 2023
• Actual Primary Completion Date: April 5, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Patients willing and able to give informed consent.
2. Patient must be, in the investigator opinion, able to comply with all the protocol procedures.
3. Age ≥18
4. Negative pregnant test in case of fertile women*
5. 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
6. 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.
7. No other chemotherapy or immunotherapy for the tumor in the four weeks previous to the inclusion
8. Karnofsky Performance Status ≥ 70 before inclusion.
9. Must have adequate renal, bone marrow and liver function.

10. 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.

Exclusion Criteria:

1. Severe infections or intercurrent medical conditions including, but not limited to, severe renal, hepatic, heart or bone marrow failure, that, on investigator´s criteria, do not allow the inclusion. Patients must be afebrile at baseline [i.e., < 38 degrees (C)].
2. Patients with an enhancing lesion bigger than 25cc, including necrotic tumor portions encircled inside the enhancing areas.
3. Subjects with immunodeficiency, autoimmune conditions or active hepatitis.
4. 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.
5. 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.
6. 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.
7. Severe bone marrow hypoplasia.
8. AST and/or ALT > 4 times over upper normal laboratory level
9. Neutrophils < 1.5 x 109/L
10. Thrombocytes ≤ 100 x 109/L
11. Hemoglobin < 9g/dl
12. Multiple lesions, extensive ill-defined diffuse lesions, or lesions considered risky for stereotactic injection of virus, like periventricular lesions.
13. Patients with Li-Fraumeni Syndrome or with a known germ line deficit in the retinoblastoma gene or its related pathways.
14. Biologic/immunotherapy (e.g., IL-2, IL-12, interferon) within 4 weeks of DNX-2440 administration.
15. Vaccination of any kind within 4 weeks prior to DNX-2440 administration.

16. Inability to undergo MRI examination for any reason.

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Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT03714334
• Other Study ID Numbers: D2440GBM1
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Clinica Universidad de Navarra, Universidad de Navarra
• Original Responsible Party: Same as current
• Current Study Sponsor: Clinica Universidad de Navarra, Universidad de Navarra
• Original Study Sponsor: Same as current
• Collaborators: DNAtrix, Inc.
• Investigators: Not Provided
• PRS Account: Clinica Universidad de Navarra, Universidad de Navarra
• Verification Date: April 2023