Conservative Treatments of Retinoblastoma

Children Clinical Trial

— RETINO2011  

Official title:

Conservative Treatments of Retinoblastoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02866136
• Other study ID #: IC 2011-05
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 2012
• Est. completion date: September 2035

Study information

• Verified date: January 2024
• Source: Institut Curie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Conservative treatments of retinoblastoma (RETINO 2011) 1. -Multicentric non randomised, phase II study for the patients treated by chemoreduction (VP16, carboplatin) followed by chemothermotherapy without laser treatment at day 8 2. -Multicentric non randomised, phase II study for the patients with bilateral very asymmetric dis-ease (Group D eye on one of the eye) or unilateral presentation groups B/C/D according to the age and vitreous seeding 3. - Multicentric non randomised, phase II study for the patients treated by 6 cycles of three drugs regimen and local treatments for bilateral group D eyes or on the only eye.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 133
• Est. completion date: September 2035
• Est. primary completion date: January 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 6 Years

Eligibility

Inclusion Criteria:

Study 1 inclusion criteria:

• Patients affected by unilateral retinoblastoma groups A, B (according to the age), group C (according to the age and vitreous seeding),or bilateral retinoblastoma groups A, B, C (excluding the eyes with macular threat and bilateral group D eyes or on the only remaining eye) amenable to a conservative treatment (at least on one eye in bilateral disease) but needing initial chemotherapy because of the location, the size of the lesion (more than 4 mm of diameter), a vision threat or risks of intravitreal relapse making those patients not amenable to chemothermotherapy first line.
• Patients less than six months of age with unilateral retinoblastoma groups B, C, D, or bilateral very asymmetric with one eye group D and the other amenable to local treatments without chemotherapy.
• Children from 0 to 6 years old.

Study 2 inclusion criteria:

• Patients affected by unilateral or bilateral retinoblastoma group B (according to the age), group C (according to the age and vitreous seeding), or group D.
• Patients affected by bilateral retinoblastoma very asymmetric with a group D eye that can be treated by intraarterial chemotherapy by Melphalan and the other amenable to local treatments without chemotherapy.
• Children from 6 months to 6 years old.

Study 3 inclusion criteria:

• Children affected of bilateral group D retinoblastoma or on the only eye amenable to conservative treatment.
• Children from 0 to 6 years old.

Common inclusion criteria:

• Patients not previously treated by chemotherapy or radiotherapy for this tumour or another cancer.
• No contra-indications to the study treatments
• Possible long term follow-up.
• Written informed consent of the parents or the legal representative.
• Patients having social security cover. Exclusion Criteria:

Study 1 exclusion criteria:

• Patients for whom a local treatment is possible without initial chemotherapy (tumour smaller than 4 mm and located far from optic nerve head or macula).
• Patients with an unilateral group D with massive tumour or group E eyes needing enucleation first line or after initial chemotherapy (in case of buphthalmia or suspected optic nerve invasion or extrascleral extension).
• Patients affected by bilateral retinoblastoma very asymmetric with a group D eye that can be treated by intraarterial chemotherapy by Melphalan and the other amenable to local treatments without chemotherapy.
• Patients with bilateral retinoblastoma and bilateral group D eyes or on the only remaining eye or presenting a bilateral macular threat requiring conservative treatment by a 6 cycles, three drugs regimen.

Study 2 exclusion criteria:

• Patients with a unilateral group D (extensive) or B or C but covering the optic nerve head or group E eyes for which enucleation is warranted first line or after chemotherapy (in case of buphthalmia or suspected optic nerve invasion or extrascleral extension).
• Patients with unilateral group D eye with tumour volume of more than 50% of eye volume, for whom a massive choroidal invasion could be associated (on clinical or imaging criteria) and for which enucleation is warranted.

Study 3 exclusion criteria:

• Patients for whom a local treatment is possible without chemoreduction (tumour smaller than 4 mm, distant from macula and from optic nerve head).
• Patients affected by bilateral retinoblastoma very asymmetric with a group D eye that can be treated by intraarterial chemotherapy by Melphalan and the other amenable to local treatments without chemotherapy.
• Patients with bilateral retinoblastoma without macular threat or groups A, B, C than can be treated with chemoreduction by VP16 and Carboplatin then chemothermotherapy without laser at day 8.

Common exclusion criteria:

• Patients older than 6 years old.
• Patients with extraocular retinoblastoma.
• Patients with a disease being a contra-indication to chemotherapy.
• Patients anteriorly treated by chemotherapy.
• Patients anteriorly treated by external beam irradiation.
• Patients anteriorly treated for another cancer.
• Follow-up not possible due to geographic distance from the center or for social or psychological reasons.
• Parents not having accepted the therapeutic strategy after explanations by the investigator.
• Contra-indication to the use of one of the drugs used in the study.

Related Conditions & MeSH terms

• Children
• Retinal Neoplasm
• Retinal Neoplasms
• Retinoblastoma

Intervention

Drug:
• VP16, carboplatin
Systemic treatment : Intravenous injections, 2 cycles (21 days)
• Melphalan
intraarterial injections, 3 to 6 cycles (1 month)
• VP16, carboplatin, vincristin
Systemic treatment : Intravenous injections, 6 cycles (21 days)
• Carboplatin + laser day 1 (chemothermotherapy)
Chemothermotherapy : Intravenous injection by carboplatin and Laser at day 1

Device:
• Laser (local treatment)

• cryoapplication (local treatment)

Radiation:
• I125 radioactive plaques (local treatment)

Drug:
• intravitreal Melphalan (local treatment)

Locations

Country	Name	City	State
France	Institut Curie	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Institut Curie	Fondation Rothschild Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of enucleation and external beam irradiation		From first day of treatment to 18 months after the end of treatments
Secondary	Number of relapses diagnosticated by fundus examination under general anesthesia until the age of 4 years, and without general anesthesia for older patients	Number of fundus examination positives without clinical symptoms and number of patients treated after fundus examination-related treatment with a controlled disease.	5 years
Secondary	Prospective evaluation of the systemic, ocular and general sides effects (short term) of the intravenous chemotherapy, intraarterial chemotherapy, combined to the local treatments as well as the intravitreal injections of Melphalan	Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 and types of adverse events occuring in order to reassess the benefice-risk scale (by Independent Data Monitoring Committee), for each arm of the study and for the whole study.	5 years
Secondary	Prospective evaluation of the systemic, ocular and general sides effects (medium and long term) of the intravenous chemotherapy, intraarterial chemotherapy, combined to the local treatments as well as the intravitreal injections of Melphalan	Rate of patient with a progression disease and/or presenting a medium/long term adverse event(s) or a second cancer.	5 years
Secondary	Response to intravitreal chemotherapy by Melphalan	Number of patients with uncontrolled disease (progression) and/or presenting Adverse Event(s) as assessed by CTCAE v4.0, related to intravitreal chemotherapy by Melphalan.	18 months
Secondary	Radiation doses received during intraarterial procedures	Time of scopies during ophthalmic arterial catheterism, doses delivered by the machine, doses received on skin.	18 months
Secondary	Number of patients presenting a long term second tumour		until 20 years old