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

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

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.

Study Overview

• Status: Completed
• Conditions: Retinoblastoma, Recurrent
• Intervention / Treatment: Genetic: VCN-01

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 Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08950
    • Hospital Sant Joan de Déu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 12 years (Child)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Histopathology of enucleated eyes after treatment with VCN-01	Presence of VCN-01 in vitreous humor samples of enucleated eyes	180 days

Collaborators and Investigators

• Sponsor: Fundació Sant Joan de Déu
• Investigators: Principal Investigator: Jaume Catalá Mora, Dr, Hospital Sant Joan de Déu

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2017
• Primary Completion (Actual): June 14, 2024
• Study Completion (Actual): June 14, 2024

Study Registration Dates

• First Submitted: August 17, 2017
• First Submitted That Met QC Criteria: September 14, 2017
• First Posted (Actual): September 15, 2017

Study Record Updates

• Last Update Posted (Actual): August 27, 2024
• Last Update Submitted That Met QC Criteria: August 26, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Gene therapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Eye Diseases; Retinal Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Eye Diseases, Hereditary; Eye Neoplasms; Retinal Neoplasms; Retinoblastoma
• Other Study ID Numbers: FSJD-RTB-2015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Anonymized individual data of participants will be shared with Authorities at the end of the Clinical development plan by the CTD (Common Technical Document). Results will be published in a scientific publication

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No