Clinical trial NCT03284268: Evaluate Safety and the Oncolitic Adenovirus VCN-01 Activity in Patients With Refractory Retinoblastoma
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Retinoblastoma, Recurrent
Keywords: Gene therapy
Lead sponsor: Fundació Sant Joan de Déu
Sponsor class: OTHER
First posted: 2017-09-15
Enrollment: 13
Sex: ALL
Minimum age (years): 1
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 180 days
Secondary outcomes:
measure: Tumor response
timeFrame: 28 days
measure: VCN-01
timeFrame: 180 days
measure: Immune response
timeFrame: 180 days
Other outcomes:
measure: Histopathology of enucleated eyes after treatment with VCN-01
timeFrame: 180 days
Locations:
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Déu
Study officials:
affiliation: Hospital Sant Joan de Deu
name: Jaume Catalá Mora, Dr
role: PRINCIPAL_INVESTIGATOR
References: