Evaluate Safety and the Oncolitic Adenovirus VCN-01 Activity in Patients With Refractory Retinoblastoma

Study Overview
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Brief Summary
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Phase I study, single site, open label with dose escalation, for evaluate safety and the oncolitic Adenovirus VCN-01 activity in patients with refractory retinoblastoma.

Official Title
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Phase I Study, Single Site, Open Label With Dose Escalation, for Evaluate Safety and the Oncolitic Adenovirus VCN-01 Activity in Patients With Refractory Retinoblastoma

Conditions
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Retinoblastoma, Recurrent

Intervention / Treatment
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* Genetic: VCN-01


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with retinoblastoma with a somatic mutation of the geneRB1 and active tumor in a single eye, or germinal mutation of RB1 with active tumor/s in an eye and the contralateral eye unaffected, enucleated or without tumor activity. In both cases, relapsed or refractory with the use of systemic, intraarterial or intravitreal chemotherapy or radiotherapy, in accordance with the availability at his/her referral site, in whom enucleation is the only recommended treatment under opinion of the medical team treating the case at the originating referral site. Normal renal function: serum creatinine: <45μmol/L (0-2 years); <57μmol/L (3-6 years); <60μmol/L (7-10 years); <80μmol/L (11-13 years). Normal Hepatic function: serum ALT: <0,52μkat/L (de 9 months -12 years); serum AST: 61-80 g/L (8 months - 5 years); 63-83 g/L (5-9 years); 63-82 g/L (9-12 years). Adequate marrow reserve manifested in an absolute neutrophil count> 1000 / mm3, platelets> 100,000 / mm3 and hemoglobin> 8 g / dl, without transfusional or cytokine support at least one month prior to study entry. Age greater than one year and less than 12 years at the time of inclusion in the study. Informed consent form signed. Exclusion Criteria: Presence of factors that require immediate enucleation of the affected eye such as glaucoma, rubeosis iridis, anterior chamber involvement. Comorbidities: Uncontrolled epilepsy with anticonvulsant treatment, cardiac disease not compensated by treatment. Active Infections. Other chronic or active acute diseases that under the criterion of the researcher were an exclusion criterion. History of having received attenuated or live vaccines in the 30 days prior to inclusion in the study. Any cause of Immunosuppression. Trilateral Retinoblastoma. Extraocular spread. History of having received treatment for retinoblastoma with chemotherapy or radiation therapy by any means within 30 days prior to inclusion in the study. Patients who can not complete the study procedures for reasons psychological or social. Pregnancy. Female patients with procreative potential should be agree to undergo a blood or urine pregnancy test and the result should be negative to enter the study.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation of VCN-01<br>Dose lower : 2E+9 viral particules/eye Dose medium: 2E+10 viral particules/eye Dose high: 2E+11 viral particules/eye | Genetic: VCN-01<br>* VCN-01 intravitreal injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | The safety and tolerability of two intravitreal injections of VCN-01 will be determined with dose escalation until the maximum tolerated dose (MTD) is established based on the evaluation of adverse events and the observation of any dose-limiting toxicity (TLD). | 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response | Tumor response rate (ORR) to VCN-01 at 28 days post-administration. | 28 days | 
| VCN-01 | Virus presence in blood samples, aqueous humor, ocular surface and nasal swabs, and its difference between the viral particles before and after the treatment to evaluate the excretion profile of the CNV-01. | 180 days | 
| Immune response | The presence of neutralizing antibodies in blood samples in study patients to assess the immune response. | 180 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gene therapy