Conservative treatment of patients with retinoblastoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut Curie

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

20 Feb 2012 → ongoing

Decision date (initial)

2024-09-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-517275-21-00

EudraCT number

2011-003621-10

ClinicalTrials.gov

NCT02866136

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

Study 1- Conservative treatment of retinobalstoma patients (unilateral group A, B according to age, C according to the age and the vitreous seeding) or bilateral groups A,B and C excluding the bilateral groups D or patients with bilateral macular threat , of intravenous chemotherapy (VP16, carboplatin) followed by chemothermotherapy without laser treatment at day 8.
To evaluate the efficacy of the treatment in terms of ocular preservation without external beam radiation for the patients treated by intravenous chemotherapy (VP16, carboplatin) followed by chemothermotherapy decreasing the laser sessions.

Study 2 - Conservative treatment of patients with groups B/C according to the age and vitreous seeding/ group D unilateral or very asymmetric with group D in one eye and the other eye amenable to a local treatment, by intra arterial Melphalan.
To evaluate the efficacy of melphalan chemotherapy administered by superselective cathetherization of the ophthalmic artery and combined to local treatments (laser treatment, cryoapplication , I125 radioactive plaques or intravitreal melphalan) in terms of ocular preservation without external beam radiation

Study 3 - Conservative treatments of patients with bilateral group D eyes or on the only remaining eye : 6 cycles of three drugs regimen combined to local treatment from the third cycle.
To evaluate the efficacy of chemotherapy and local treatments (laser treatment, cryoapplication, I125 plaques or intra vitreal melphalan) in terms of ocular preservation without external beam radiation.

Secondary objectives 4

1. To continue the evaluation of the conservative strategy (local treatments after a phase of chemoreduction for the patients that cannot be treated directly without chemotherapy, the efficacy of the 3 drugs regimen and local treatment and of intra-arterial and intravitreal chemotherapies.
2. To realize a prospective study of the sides effects (ocular and systemic) at short, medium and long term follow-up of the intravenous chemotherapy, and intra-arterial, alone or combined to local ocular treatments.
3. Dosimetric study of the radiation doses received during the intra-arterial procedures.
4. To evaluate the second tumours occurring at long term follow up.

Conditions and MedDRA coding

Retinoblastoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Overall study inclusion criteria: Patients not previously treated by chemotherapy or radiotherapy for this tumour or another cancer.
2. Overall study inclusion criteria: Possible long term follow-up.
3. Overall study inclusion criteria: Written informed consent of the parents or the legal representative.
4. Overall study inclusion criteria: Patients having social security cover.
5. Overall study inclusion criteria: No contra-indications to the study treatments.
6. Studies 1 and 3 inclusion criteria : Children from 0 to 6 years old.
7. 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.
8. Study 1 inclusion criteria : 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.
9. 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.
10. Study 2 inclusion criteria: 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.
11. Study 2 inclusion criteria: Children from 6 months to 6 years old.
12. Study 3 inclusion criteria: Children affected of bilateral group D retinoblastoma or on the only eye amenable to conservative treatment.

Exclusion criteria 18

1. Overall study non-inclusion criteria: Patients older than 6 years old.
2. Overall study non-inclusion criteria: Patients with extraocular retinoblastoma.
3. Overall study non-inclusion criteria: Patients with a disease being a contra-indication to chemotherapy.
4. Overall study non-inclusion criteria: Patients anteriorly treated by chemotherapy.
5. Overall study non-inclusion criteria: Patients anteriorly treated by external beam irradiation.
6. Overall study non-inclusion criteria: Patients anteriorly treated for another cancer.
7. Overall study non-inclusion criteria: Follow-up not possible due to geographic distance from the center or for social or psychological reasons..
8. Overall study non-inclusion criteria: Parents not having accepted the therapeutic strategy after explanations by the investigator.
9. Overall study non-inclusion criteria: Contra-indication to the use of one of the drugs used in the study.
10. Study 1 non-inclusion 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).
11. Study 1 non-inclusion criteria: 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).
12. Study 1 non-inclusion criteria: 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.
13. Study 1 non-inclusion criteria: 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.
14. Study 2 non-inclusion criteria: Patients with a unilateral group D (extensive) or B or C or D 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).
15. Study 2 non-inclusion criteria: 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.
16. Study 3 non-inclusion criteria: Patients for whom a local treatment is possible without chemoreduction (tumour smaller than 4 mm, distant from macula and from optic nerve head).
17. Study 3 non-inclusion criteria: 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.
18. Study 3 non-inclusion criteria: 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 treatment at day 8.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. For the 3 studies: ocular preservation (absence of secondary enucleation) and absence of external beam radiotherapy at 18 months.

Secondary endpoints 5

1. Evaluation or the risk of relapse by fundus examination under general anaesthesia until the age of 4 then without general anaesthesia.
2. Prospective evaluation of the ocular and general side effects (short, medium and long term) of the intravenous chemotherapy, intra-arterial chemotherapy, combined to the local treatment as well as the intra-vitreal injections of melphalan.
3. Evaluation of the response to intra-vitreal chemotherapy by melphalan.
4. Study of the radiation doses received during intra-arterial procedures.
5. Evaluate the number of patients presenting with another tumour.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut Curie

Sponsor organisation

Institut Curie

Address

26 Rue D Ulm

City

Paris

Postcode

75005

Country

France

Scientific contact point

Organisation

Institut Curie

Contact name

Livia LUMBROSO

Public contact point

Organisation

Institut Curie

Contact name

Livia LUMBROSO

Locations

1 EU/EEA country · 27 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

1 submissions — initial application plus substantial / non-substantial modifications