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Conservative Treatments of Retinoblastoma (RETINO2011)

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ClinicalTrials.gov Identifier: NCT02866136
Recruitment Status : Recruiting
First Posted : August 15, 2016
Last Update Posted : March 21, 2019
Sponsor:
Collaborator:
Fondation Rothschild Paris
Information provided by (Responsible Party):
Institut Curie

Brief 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.

Condition or disease Intervention/treatment Phase
Retinoblastoma Children Retinal Neoplasm Drug: VP16, carboplatin Drug: Melphalan Drug: VP16, carboplatin, vincristin Drug: Carboplatin + laser day 1 (chemothermotherapy) Device: Laser (local treatment) Device: cryoapplication (local treatment) Radiation: I125 radioactive plaques (local treatment) Drug: intravitreal Melphalan (local treatment) Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 133 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Conservative Treatments of Retinoblastoma
Study Start Date : February 2012
Actual Primary Completion Date : February 28, 2019
Estimated Study Completion Date : February 2027

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
(IV)Intravenous chemotherapy, laser diode

Group 1 - Multicentric non randomised, phase II study for patients with retinoblastoma (unilateral group A,B according to age, group 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).

Treatment by chemoreduction (VP16, carboplatin) followed by Carboplatin + laser day 1 (chemothermotherapy) without laser treatment at day 8 (decreasing laser sessions) combined to local treatments from third course (laser, cryoapplication, I125 radioactive plaques or intravitreal Melphalan).

Drug: VP16, carboplatin
Systemic treatment : Intravenous injections, 2 cycles (21 days)
Other Name: etoposide, vepesid, chemotherapy

Drug: Carboplatin + laser day 1 (chemothermotherapy)
Chemothermotherapy : Intravenous injection by carboplatin and Laser at day 1
Other Name: Carbo-laser, platinum-based chemotherapy

Device: Laser (local treatment)
Other Name: Laser diode

Device: cryoapplication (local treatment)
Radiation: I125 radioactive plaques (local treatment)
Drug: intravitreal Melphalan (local treatment)
(IA) Intraarterial Melphalan

Group 2 - Multicentric non randomised, phase II study for the patients with bilateral very asymmetric disease (group D retinoblastoma on one of the eye, and the other amenable to a local treatment without chemotherapy) or unilateral presentation group D and groups B/C according to the age and vitreous seeding.

Treatment by Melphalan chemotherapy administered by superselective catheterization of the ophthalmic artery and combined to local treatments (laser, cryoapplication, I125 radioactive plaques or intravitreal Melphalan).

Drug: Melphalan
intraarterial injections, 3 to 6 cycles (1 month)
Other Name: Alkeran, chemotherapy

Device: Laser (local treatment)
Other Name: Laser diode

Device: cryoapplication (local treatment)
Radiation: I125 radioactive plaques (local treatment)
Drug: intravitreal Melphalan (local treatment)
(IV-PM) Intravenous 3 drugs chemotherapy
Group 3 - Multicentric non randomised, phase II study for the patients with bilateral group D retinoblastoma or with a group D retinoblastoma on the only remaining eye. Treatment by 6 cycles of three drugs (VP16, carboplatin, vincristin) regimen combined to local treatments from the third cycle (laser, cryoapplication, I125 radioactive plaques or intravitreal Melphalan).
Drug: VP16, carboplatin, vincristin
Systemic treatment : Intravenous injections, 6 cycles (21 days)
Other Name: etoposide, vepesid, leurocristine, Oncovin, chemotherapy

Device: Laser (local treatment)
Other Name: Laser diode

Device: cryoapplication (local treatment)
Radiation: I125 radioactive plaques (local treatment)
Drug: intravitreal Melphalan (local treatment)



Primary Outcome Measures :
  1. Rate of enucleation and external beam irradiation [ Time Frame: From first day of treatment to 18 months after the end of treatments ]

Secondary Outcome Measures :
  1. Number of relapses diagnosticated by fundus examination under general anesthesia until the age of 4 years, and without general anesthesia for older patients [ Time Frame: 5 years ]
    Number of fundus examination positives without clinical symptoms and number of patients treated after fundus examination-related treatment with a controlled disease.

  2. 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 [ Time Frame: 5 years ]
    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.

  3. 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 [ Time Frame: 5 years ]
    Rate of patient with a progression disease and/or presenting a medium/long term adverse event(s) or a second cancer.

  4. Response to intravitreal chemotherapy by Melphalan [ Time Frame: 18 months ]
    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.

  5. Radiation doses received during intraarterial procedures [ Time Frame: 18 months ]
    Time of scopies during ophthalmic arterial catheterism, doses delivered by the machine, doses received on skin.

  6. Number of patients presenting a long term second tumour [ Time Frame: until 20 years old ]


Information from the National Library of Medicine

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Ages Eligible for Study:   up to 6 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02866136


Contacts
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Contact: Livia Lumbroso-Le Rouic, MD 33(0)1 44 32 46 02
Contact: Souhir Neffati souhir.neffati@curie.fr

Locations
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France
Institut Curie Recruiting
Paris, France, 75005
Contact: Isabelle Aerts, MD    01 44 32 45 51    isabelle.aerts@curie.fr   
Sponsors and Collaborators
Institut Curie
Fondation Rothschild Paris
Investigators
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Study Director: Isabelle Aerts, MD Institut Curie - Paris - France
Principal Investigator: Catherine Devoldere, MD Amiens (FR), University College Hospital
Principal Investigator: Isabelle Pellier, MD Angers (FR), University College Hospital
Principal Investigator: Véronique Laithier, MD Besançon (FR), Jean Minjoz Hospital
Principal Investigator: Celine De Bouyn-Icher, MD Bordeaux (FR), Pellegrin Regional Hospital
Principal Investigator: Liana-Stephania Carausau, MD Brest (FR), University College Hospital
Principal Investigator: Odile Minckes, MD Caen (FR), University College Hospital
Principal Investigator: Justyna Kanold, MD Clermont-Ferrand (FR), University College Hospital
Principal Investigator: Claire Briandet, MD Dijon (FR), Bocage University College Hospital
Principal Investigator: Dominique Plantaz, Prof. Grenoble (FR), University College Hospital
Principal Investigator: Hélène Sudour-Bonnange, MD Lille (FR), Oscar Lambret Center
Principal Investigator: Christophe Piguet, MD Limoges (FR), University College Hospital
Principal Investigator: Cécile Faure Conter, MD Lyon (FR), Leon Berard Center
Principal Investigator: Carole Coze, MD Marseille (FR), La Timone Children Hospital
Principal Investigator: Nicolas Sirvent, MD Montpellier (FR), Arnaud de Villeneuve Hospital
Principal Investigator: Ludovic Mansuy, MD Nancy (FR), University College Hospital
Principal Investigator: Estelle Thebaud, MD Nantes (FR), University College Hospital
Principal Investigator: Marilyne Dupuy-Poiree, MD Nice (FR), University College Hospital
Principal Investigator: Frederic Millot, MD Poitiers (FR), University College Hospital
Principal Investigator: Claire Pluchart, MD Reims (FR), Regional University College Hospital
Principal Investigator: Celine Chappe, MD Rennes (FR), University College Hospital
Principal Investigator: Pascale Schneider, Prof. Rouen (FR), University College Hospital
Principal Investigator: Jean-Louis Stephan, Prof. Saint-Etienne (FR), University College Hospital
Principal Investigator: Natacha Entz-Werle, MD Strasbourg (FR), University College Hospital
Principal Investigator: Anne-Isabelle Bertozzi-Salamon, MD Toulouse (FR), Children Hospital
Principal Investigator: Pascale BLOUIN, MD Tours (FR), University College Hospital
Principal Investigator: Michel Piotin, MD Paris (FR), Adolphe Rothschild Ophtalmologic Foundation

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Responsible Party: Institut Curie
ClinicalTrials.gov Identifier: NCT02866136     History of Changes
Other Study ID Numbers: IC 2011-05
First Posted: August 15, 2016    Key Record Dates
Last Update Posted: March 21, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
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Retinoblastoma
Retinal Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Eye Neoplasms
Neoplasms by Site
Eye Diseases, Hereditary
Eye Diseases
Retinal Diseases
Carboplatin
Etoposide
Etoposide phosphate
Melphalan
Vincristine
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors