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

Not Applicable

Completed

• Conditions: Retinoblastoma, Recurrent
• Interventions: Genetic: VCN-01

• Registration Number: NCT03284268
• Lead Sponsor: Fundació Sant Joan de Déu

Brief Summary

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.

Detailed Description

Phase I clinical trial, single-center, open-label, dose-escalation study, to evaluate the safety of the VCN-01 and, secondarily, its anti-tumoral activity. The trial sample consists of approximately 13 patients aged between 1 and 12 years old.

Study Timeline

• Study First Submitted: 2017-08-17
• Study Start: 2017-09-06
• Study First Submitted QC: 2017-09-14
• Study First Posted: 2017-09-15
• Primary Completion: 2024-06-14
• Study Completion: 2024-06-14
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-26
• Last Update Posted: 2024-08-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

1. 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.
2. 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).
3. 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).
4. 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.
5. Age greater than one year and less than 12 years at the time of inclusion in the study.
6. Informed consent form signed.

Exclusion Criteria

1. Presence of factors that require immediate enucleation of the affected eye such as glaucoma, rubeosis iridis, anterior chamber involvement.
2. Comorbidities: Uncontrolled epilepsy with anticonvulsant treatment, cardiac disease not compensated by treatment.
3. Active Infections.
4. Other chronic or active acute diseases that under the criterion of the researcher were an exclusion criterion.
5. History of having received attenuated or live vaccines in the 30 days prior to inclusion in the study.
6. Any cause of Immunosuppression.
7. Trilateral Retinoblastoma.
8. Extraocular spread.
9. History of having received treatment for retinoblastoma with chemotherapy or radiation therapy by any means within 30 days prior to inclusion in the study.
10. Patients who can not complete the study procedures for reasons psychological or social.
11. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dose escalation of VCN-01	VCN-01	Dose lower : 2E+9 viral particules/eye Dose medium: 2E+10 viral particules/eye Dose high: 2E+11 viral particules/eye

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events	180 days	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).

Secondary Outcome Measures

Name	Time	Method
Tumor response	28 days	Tumor response rate (ORR) to VCN-01 at 28 days post-administration.
VCN-01	180 days	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.
Immune response	180 days	The presence of neutralizing antibodies in blood samples in study patients to assess the immune response.

Trial Locations

Locations (1)

Hospital Sant Joan de Déu; 🇪🇸 Barcelona, Spain