RETINO2018: Ocular Conservative Treatment for Retinoblastoma : Efficacy of the New Management Strategies and Visual Outcome

• Sponsor: Institut Curie (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04681417
• Collaborator: Fondation Rothschild Paris (Other)
• Enrollment: 225
• Locations: 28
• Arms: 2
• Anticipated Duration (Months): 177.9
• Patients Per Site: 8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This protocol includes 2 independent studies. Both studies are multicenter studies, evaluating different therapeutic approaches in two different populations of patients:

• Study 1, a randomized phase-II study evaluating the efficacy of Intra-Arterial Chemotherapy (IAC) with melphalan and topotecan versus melphalan alone, both in association with ophthalmologic treatments.

• Study 2, a minimally invasive interventional study evaluating the results on visual function following reference treatment with intravenous (IV) chemotherapy in association with ophthalmologic treatments.

Condition or Disease	Intervention/Treatment	Phase
Retinoblastoma	Drug: Melphalan or Melphalan + Topotecan; Drug: etoposide, carboplatin and vincristine; Drug: Carboplatin administered on Day 1; Device: Thermotherapy (local treatment); Device: Cryotherapy (local treatment); Device: Iodine-125 plaques (local treatment); Drug: Intravitreal Melphalan chemotherapy injections (local treatment)	Phase 2/Phase 3

Detailed Description

Primary objective of the studies:

• Study 1: To evaluate the efficacy of IAC in term of local control of the disease in patients eligible for IAC (randomized phase II study);

• Study 2: To assess the visual function, based on World Health Organization (WHO) criteria, in patients eligible for other conservative treatments (IV chemotherapy in association with local ophthalmologic treatments; this is a minimally invasive interventional study).

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 225 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Ocular Conservative Treatment for Retinoblastoma: Efficacy of the New Management Strategies and Visual Outcome - RETINO 2018
• Actual Study Start Date: Mar 25, 2021
• Anticipated Primary Completion Date: Jan 20, 2035
• Anticipated Study Completion Date: Jan 20, 2036

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Study 1: Melphalan or Melphalan + Topotecan Randomized phase-II study evaluating the efficacy of Intra-Arterial Chemotherapy (IAC) with melphalan and topotecan versus melphalan alone, both in association with ophthalmologic treatments.	Drug: Melphalan or Melphalan + Topotecan; IAC: 2-6 cycles every 1 month (number based on the local tumor evolution), performed using radio-guided catheterization and delivery at the ostium of the ophthalmic artery, in neuroradiology operating room, and under General Anesthesia (GA). IAC will be administered at the Fondation Rothschild Hospital in collaboration with the Interventional Neuroradiology team.; Other Names: Alkeran, Topotecan Accord; Topotecan Hospira chemotherapy ; Device: Thermotherapy (local treatment); Thermotherapy after carboplatin administered on Day 1; Other Names: Thermotherapy after carboplatin administered on Day 1 ; Device: Cryotherapy (local treatment); Cryotherapy (local treatment); Device: Iodine-125 plaques (local treatment); Iodine-125 plaques (local treatment); Drug: Intravitreal Melphalan chemotherapy injections (local treatment); Intravitreal Melphalan chemotherapy injections (local treatment)
Other: Study 2: Etoposide, carboplatin and vincristine Neoadjuvant chemotherapy involves 2 to 6 cycles of combined etoposide, carboplatin and vincristine in association with ophthalmologic treatments.	Drug: etoposide, carboplatin and vincristine; 2 to 6 cycles of combined etoposide, carboplatin and vincristine; Other Names: etoposide, carboplatin and vincristine chemotherapy ; Drug: Carboplatin administered on Day 1; Chemothermotherapy : Intravenous injection by carboplatin; Other Names: platinum-based chemotherapy ; Device: Thermotherapy (local treatment); Thermotherapy after carboplatin administered on Day 1; Other Names: Thermotherapy after carboplatin administered on Day 1 ; Device: Cryotherapy (local treatment); Cryotherapy (local treatment); Device: Iodine-125 plaques (local treatment); Iodine-125 plaques (local treatment); Drug: Intravitreal Melphalan chemotherapy injections (local treatment); Intravitreal Melphalan chemotherapy injections (local treatment)

Outcome Measures

Primary Outcome Measures

1. Study 1: Rate of eye preservation [24 months after randomization]

   Rate of eye preservation in the 2 treatments' arms

2. Visual function [when patient is 6 years old and at least 24 months of follow-up after study inclusion]

   Percentage of patients with major, mild or no impairment of visual function according to WHO criteria, i.e. normal bilateral visual acuity (≥ 6/10) or mild bilateral visual impairment (3/10 to 5/10) according to tumor location and extension

Secondary Outcome Measures

1. Ocular toxicity [Up to 24 months after inclusion in the study]

   Percentage of patients with at least one grade-3 or -4 toxicity (CTCAE v. 5.0)

2. Systemic toxicity [Up to 24 months after inclusion in the study]

   Rate of specific grade 3-4 toxicity (CTCAE v. 5.0)

3. Relapse [within 24 months after inclusion]

   Percentage of patients with relapse within 24 months after inclusion, broken down into: Local relapse, Extra-ocular relapse

4. Second malignant tumor [24 months after study inclusion]

   Percentage of patients with second malignant tumor within 24 months after study inclusion

5. Additional assessment of visual function [In the year patients turn 6 years of age and at least 24 months of treatment]

   Additional assessment of visual function at follow-up: Percentage of patients at each of the four levels of visual acuity according to WHO criteria

6. Retinal assessment [In the year patients turn 6 years of age and at least 24 months of treatment]

   Optical Coherence Tomography (OCT) and Optical Coherence Tomography-Angiography (OCT-A) measures on retina

7. Integration at school [In the year patients turn 6 years of age and at least 24 months of treatment]

   Rate of children able to attend the common primary school : without specific help or with the help of a dedicated person and/or with specific features to facilitate reading and writing

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Months to 6 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Overall study inclusion criteria:

1. Newly diagnosed retinoblastoma (RB).

2. Retinoblastoma with at least one eye eligible for conservative management.

3. Patients likely to be compliant with the study requirements and visits, including late follow-up.

4. Patients not previously treated with chemotherapy or radiotherapy for this or any other cancer.

5. Patients with no contraindication to the proposed treatments.

6. Informed consent signed by parents or legal representative.

7. French Social Security System coverage.

Study 1 inclusion criteria:

8.1. Children aged from 6 months to 6 years. 9. Retinoblastoma in at least one eye, deemed manageable with IAC in one side and without IV chemotherapy:

1. Unilateral Retinoblastoma classified as group B, C (if vitreous seeds < 3 mm), D or E with no invasion of the anterior segment, and without massive tumor of more than 2/3 of the eye, eligible for conservative management, or

2. Bilateral Retinoblastoma but with very unbalanced lesions between the two eyes: one eye group D or E without invasion of the anterior segment or massive tumor of more than 2/3 of the eye, eligible for IAC, and the other eye eligible for local treatment only (without IAC).

Study 2 inclusion criteria:

8.2. Retinoblastoma eligible for conservative management although not manageable with IAC:

1. Unilateral Retinoblastoma in children below 6 months of age, classified as Group A, B, C or D, with or without vitreous seeding, compatible with conservative management, or

2. Bilateral Retinoblastoma classified as group A, B, C D, or E without invasion of the anterior segment, and/or massive tumors of more than 2/3 of the eye and eligible for conservative management.

Exclusion Criteria:

Overall study non-inclusion criteria:

1. RB not eligible for conservative management :

2. Extra-ocular extension of the disease, or

3. Group E eyes with invasion of the anterior segment, and/or massive tumors of more than 2/3 of the eye.

4. Patient older than 6 years of age.

5. Patients with another associated disease contra indicating systemic chemotherapy.

6. Previously treated retinoblastoma by chemotherapy.

7. Patients already treated for another malignant disease.

8. Patient with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

9. Patients whose parents have not accepted the treatment regimen after explanation of it.

10. Contraindication to study drug mentioned in SmPC (Summary of Products Characteristics) of the study drugs.

11. Inclusion in another experimental anti-cancer drug therapy.

Study 1 non-inclusion criteria:

1. Any contraindication or concomitant disease that would preclude the Study 1 treatment procedure and could delay treatment.

These patients should be eligible for Study 2.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	La Reunion - Chr Felix Guyon	Saint-Denis	La Réunion	France	97405
2	Amiens Chu	Amiens		France	80054
3	Angers Chu	Angers		France	49033
4	BESANCON CHU Hopital Jean Minjoz	Besancon		France	25030
5	Bordeaux Chu	Bordeaux		France	33076
6	BREST CHRU Hopital Morvan	Brest		France	29609
7	CAEN CHU	Caen		France	14033
8	CHU ESTAING Centre Régional de Cancérologie et Therapie Cellulaire Pediatrique (CRCTCP)	Clermont-Ferrand		France	63003
9	DIJON CHU Hopital François Mitterand	Dijon		France	21079
10	Grenoble Chu	Grenoble		France	38045
11	LILLE Centre Oscar Lambret	Lille		France	59037
12	Limoges Chu	Limoges		France	87042
13	LYON Centre Léon Bérard	Lyon		France	69373
14	Marseille Chu	Marseille		France	13385
15	MONTPELLIER CHU Hopital Arnaud De Villeneuve	Montpellier		France	34295
16	NANTES CHU Hopital Mere-Enfant	Nantes		France	44093
17	NICE CHU Hopital Archet 2	Nice		France	06202
18	Institut Curie	Paris		France	75005
19	PARIS Fondation Ophtalmologique Adolphe de Rothschild	Paris		France	75019
20	Poitiers Chu	Poitiers		France	86021
21	Reims Chu	Reims		France	51092
22	Rennes Chu	Rennes		France	35056
23	Rouen Chu	Rouen		France	76000
24	Saint Etienne Chu	Saint Etienne		France	42055
25	Strasbourg Chu	Strasbourg		France	67098
26	Toulouse Chu	Toulouse		France	31026
27	TOURS CHU Hopital Clocheville	Tours		France	37044
28	Nancy Chu	Vandoeuvre Les Nancy		France	54500

Sponsors and Collaborators

• Institut Curie
• Fondation Rothschild Paris

Investigators

• Principal Investigator: Livia LUMBROSO LE ROUIC, MD, Institut Curie

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Institut Curie
• ClinicalTrials.gov Identifier: NCT04681417
• Other Study ID Numbers: IC 2019-05
• First Posted: Dec 23, 2020
• Last Update Posted: Jan 12, 2022
• Last Verified: Jan 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Institut Curie: Pediatric; Ocular conservative treatment in retinoblastoma
• Additional relevant MeSH terms: Retinoblastoma; Carboplatin; Etoposide; Etoposide phosphate; Vincristine; Melphalan; Topotecan

Study Results

No Results Posted as of Jan 12, 2022