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Virus Therapy

Virus-Based Drug Therapy for Brain Tumor (rQNestin Trial)

Phase 1

Recruiting

Led By E. Antonio Chiocca, MD, PhD

Research Sponsored by Dana-Farber Cancer Institute

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Frozen biopsy consistent with glioma by neuropathologist at the time of the first surgery in this longitudinal trial

Participants must have prior diagnosis of IDH wild-type glial tumor including GBM, grade 3 anaplastic astrocytoma or oligodendroglioma or grade 2 astrocytoma with genetic features consistent with GBM, as confirmed by a neuropathologist or by a previous local pathology report

Must not have

Known chronic infections with HIV, hepatitis B or C

Participants with active viral, bacterial or fungal infection requiring concurrent antiviral or antibiotics

Timeline

Screening 3 weeks

Treatment Varies

Follow Up evaluated every 2 months for 1 year

Awards & highlights

Summary

This trial is testing the safety of a new virus-based drug for brain tumors. If it is safe, they will also test what dose is most effective.

Who is the study for?

Adults over 18 with recurrent brain tumors who've had prior radiation and chemotherapy, have a Karnofsky Performance Score ≥70, and can tolerate multiple biopsies. They must not be pregnant or breastfeeding, agree to use contraception, and have no severe infections or immune disorders. Tumors must meet specific size/location criteria.

What is being tested?

The trial is testing rQNestin34.5v.2, an investigational oncolytic virus for safety and proper dosage against recurrent malignant glioma. It includes cyclophosphamide treatment and stereotactic biopsy in a Phase I clinical setting.

What are the potential side effects?

Potential side effects may include typical reactions to viruses such as fever, fatigue, headache; possible local effects at the injection site; immune responses like inflammation; plus any side effects from cyclophosphamide like nausea or low blood cell counts.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My first surgery biopsy confirmed I have glioma.

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I have been diagnosed with a specific type of brain tumor that is not IDH mutant.

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I have received temozolomide with radiation as standard treatment before.

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My blood, kidney, and liver tests are normal.

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I am able to care for myself but may not be able to do active work.

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I still have some tumor left or this is my first or second time cancer has come back.

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I am 18 years old or older.

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My MRI shows my cancer meets specific size and location criteria.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a chronic infection with HIV, hepatitis B, or C.

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I am currently being treated for an active infection.

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I am currently being treated for an active HSV-1 infection.

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I have a condition that weakens my immune system.

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My tumor size or location does not exclude me from the trial.

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I have an active tuberculosis infection.

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I haven't had severe bleeding in the last 6 months.

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I do not have any uncontrolled illnesses.

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I have a bleeding disorder or had significant bleeding in the last year.

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I have been treated with drugs targeting VEGF or VEGFR.

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I need continuous blood thinners that can't be stopped for surgery or biopsy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ evaluated every 2 months for 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~evaluated every 2 months for 1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and evaluated every 2 months for 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum Tolerated Dose

Secondary study objectives

HSV1 Antibody Response

HSV1 Viremia

MRI Changes in Flow

+3 more

Side effects data

From 2023 Phase 2 trial • 27 Patients • NCT04002401

88%

Pyrexia

65%

Neutrophil count decreased

62%

Nausea

58%

Hypotension

50%

Anaemia

46%

Headache

38%

Fatigue

38%

Decreased appetite

35%

Confusional state

31%

Diarrhoea

31%

Tachycardia

31%

Hypokalaemia

27%

Constipation

27%

Hypophosphataemia

27%

Back pain

23%

Dizziness

23%

Tremor

23%

B-cell lymphoma

23%

Platelet count decreased

23%

White blood cell count decreased

19%

Agitation

19%

Cough

19%

Hypogammaglobulinaemia

19%

Tachypnoea

19%

Neutropenia

19%

Oedema peripheral

19%

Hyponatraemia

15%

Alanine aminotransferase increased

15%

Dyspnoea

15%

Dysphagia

15%

Chills

15%

Thrombocytopenia

15%

Sinus tachycardia

15%

Hypomagnesaemia

12%

Aspartate aminotransferase increased

12%

Peripheral sensory neuropathy

12%

Hypoxia

12%

Hypertension

12%

Covid-19

12%

Vomiting

12%

Abdominal pain

12%

Pain

12%

Malaise

12%

Hyperglycaemia

12%

Arthralgia

12%

Myalgia

Dysuria

Insomnia

Urinary tract infection

Lymphocyte count decreased

Encephalopathy

Hyperhidrosis

Somnolence

Oral candidiasis

Blood creatinine increased

Asthenia

Pneumonia

Sepsis

Acute myeloid leukaemia

Pancytopenia

Eye pain

Gait disturbance

Muscular weakness

Aphasia

Depression

Febrile neutropenia

Covid-19 pneumonia

Syncope

Pleural effusion

Respiratory failure

Embolism

100%

80%

60%

40%

20%

Study treatment Arm

Axicabtagene Ciloleucel and Rituximab Combination

Trial Design

3Treatment groups

Experimental Treatment

Group I: Arm C- Multiple Dose rQNestinExperimental Treatment2 Interventions

Arm C includes up to 6 intratumoral repeated doses of rQNestin34.5v.2, first in a cohort receiving 10\^8 pfus per time point, followed by a cohort receiving 10\^9 or 10\^7 pfus per time point. * Arm C adds 2 cohorts of 12 subjects in an open-label clinical trial of rQNestin34.5v.2 administered at two dose levels * The injections are planned for days 0, 15, 30, 60, 90, and 120 * Subjects with presumed radiologic evidence of recurrent malignant glioma will undergo stereotactic biopsy under monitored general or local anesthesia. Evidence of recurrent high grade or malignant must be found on frozen section for the person to receive administration of the agent.

Group II: Arm B- rQNestin+CPAExperimental Treatment3 Interventions

Arm B is rQNestin34.5v.2 treatment with Cyclophosphamide (CPA) pre-treatment This study follows a standard 3+3 dose escalation design. Participants will not enroll to Arm B until the MTD or HTD has been met for Arm A. * Cyclophosphamide one intravenous injection 2 days prior to procedure. * Subjects with presumed radiologic evidence of recurrent malignant glioma will undergo stereotactic biopsy under monitored general or local anesthesia. Evidence of recurrent high grade or malignant must be found on frozen section for the person to receive administration of the agent. * rQNestin34.5v.2 Indicated dose as per cohort, Intratumor administration during surgery, single dose

Group III: Arm A- rQNestinExperimental Treatment2 Interventions

Arm A is rQNestin34.5v.2 treatment This study follows a standard 3+3 dose escalation design. Participants will not enroll to Arm B until the MTD or HTD has been met for Arm A. * Subjects with presumed radiologic evidence of recurrent malignant glioma will undergo stereotactic biopsy under monitored general or local anesthesia. Evidence of recurrent high grade or malignant must be found on frozen section for the person to receive administration of the agent. * rQNestin34.5v.2 Indicated dose as per cohort, Intratumor administration during surgery, single dose

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cyclophosphamide

FDA approved

0 / 19Eligibility criteria met