A Phase I clinical trial to evaluate the safety and the activity of the oncolytic adenovirus VCN-01 in patients with refractory retinoblastoma
- Conditions
- Refractory RetinoblastomaMedDRA version: 20.0Level: PTClassification code 10038916Term: RetinoblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-001060-11-ES
- Lead Sponsor
- Fundació Sant Joan de Déu
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- Not specified
1. Patients with retinoblastoma both with somatic mutation of the RB1gen with active tumor in a single eye, as with germinal mutation of the RB1gen with active tumor in a single eye and the not affected fellow eye or with active tumor in a single eye and the fellow eye already enucleated relapsed or refractories with the use of systemic chemotherapy, intra-arterial or intravitreal or radiotherapy in whom enucleation is the only advisable treatment.
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 liver function: serum ALT: <0,52µkat/L (from 9 months to 12 years); serum AST: 61-80 g/L (from 8 months to 5 years); 63-83 g/L (5-9 years); 63-82 g/L (9-12 years).
4. Adequate bone-marrow reserve expressed in an absolute neutrophil count > 1000/mm3, platelets >100.000/mm3 and hemoglobin >8 g/dl, without transfusional support.
5. Older than one year and youger than 12 years at the time of inclusion in the study.
6. Signed informed consent form.
Are the trial subjects under 18? yes
Number of subjects for this age range: 13
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Presence of factors that require immediate enucleation of the affected eye as can be glaucoma, rubeosis iridis, commitment on the anterior chamber.
2. Comorbidity situations: uncontrolled epilepsy with anticonvulsant treatment, no compensated cardiological disease with the treatment.
3. Active infections.
4. Other chronic or acute active diseases that would be an exclusion criteria under the criterion of the investigator.
5. Having received attenuated or live vaccines background in the 30 days prior to the inclusion in the study.
6. Immunosuppression of any cause.
7. Trilateral retinoblastoma.
8. Extraocular extension.
9. Antecedent of having received treatment for retinoblastoma with chemotherapy or radiotherapy by any route in the 30 days before the inclusion in the study.
10. Patients who cannot complete the study procedures for psychological or social reasons.
11. Pregnancy. Female potential of childbearing patients should agree with doing a blood or urine pregnancy test and the result shall be negative to enter into the study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determinate safety and tolerability of two intravitreal injections of VCN-01 through the evaluation of the adverse events and the laboratory tests to set the maximum tolerated dose (MTD) of the VCN-01 virus.;Primary end point(s): Safety and tolerability: Safety and tolerability of two intravitreal injections of VCN-01.;Timepoint(s) of evaluation of this end point: Throughout all study;Secondary Objective: - To evaluate the anti-tumor response of VCN-01 in patients with advanced intraocular retinoblastoma with vitreous seeding massive within the limitations imposed by the phase I design of the study.<br>- To evaluate the excretion profile of VCN-01.<br>- To evaluate the immune response by the presence of neutralizing antibodies in the patients of the study.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): *Tumor response rate (TRT) to VCN-01 28 days after administration. For this purpose it shall be defined as:<br>- Response to treatment: do not meet progressive disease (PD) criteria and notes inactivation, calcification or reduction volume in at least a vitreous seeding or retinal tumor<br>- Progressive disease (PD): clear progression of the disease, marked by an increase of tumor volume, of retinal detachment, of vitreous seeding or commitment on the anterior chamber<br>- Stable disease: no changes to the current situation for inclusion in the study<br><br>* Presence of the virus in blood samples, aqueous humor, swab of ocular or nasal surface and its difference between viral particles before and after the treatment to evaluate the excretion profile of the VCN-01<br><br>* Presence of neutralizing antibodies in blood samples in the patients of the study to evaluate the immune response;Timepoint(s) of evaluation of this end point: Day 0, 1, 2, 7, 15, 16, 21, 28, 42 y 180