A Prospective International Multicenter Clinical Trial for Eyes With Relapsed Retinoblastoma

NCT04455139 | Terminated Phase 2 DMC

• 1 other identifier: 2018-01967
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

While 95% of patients with retinoblastoma can be cured nowadays, treatment of relapse remains challenging, ending often in enucleation and/or radiotherapy. In the last 10 years, new treatment modalities have been developed to give the chance of cure also in relapse, avoiding enucleation which results in esthetic sequelae and orbital growth problems, and radiotherapy which significantly increases the risk of secondary cancers in hereditary retinoblastoma. The current protocol aims at covering all types of relapses in retinoblastoma, with treatments adapted to the site of relapse, at harmonizing the new eye- and vision-preserving treatment procedures, and evaluating their efficacy and toxicity.

Conditions

Eye Cancer, Retinoblastoma

Keywords

relapsed retinoblastoma; relapse of retinoblastoma

Outcome Measures

Primary Outcomes (2)

• Rate of retinal toxicity of intravitreous administration of melphalan versus topotecan assessed by CTCAE v5.0

  parameters: salt and pepper retinopathy, choroidopathy, number of injections until toxicity

  at 1 month after treatment completion

• Relapse rate after IAC by melphalan only and IAC by melphalan + topotecan

  parameter: eye retention rate

  at 2 years of follow-up

Secondary Outcomes (7)

• Efficacy of intravitreous topotecan compared to intravitreous melphalan (number of injections to tumor clearance in vitreous)

  at 3 or 6 months after last intravitreous injection

• Ocular survival (eye salvage rate)

  at 2 years since study entry

• Number of participants with ocular (non retinal) and systemic toxicity assessed by CTCAE v5.0

  Weekly (IVitC) or monthly (IAC) during treatment, at end of treatment (1 month after last injection), at 6, 12 and 24 months, yearly until 60 months

• Quality of vision assessed by visual acuity

  at 5 years of age

• Incidence of early (within 1 month), intermediate (2-12 months) and late (> 12 months) ocular and systemic general adverse events during regular ophthalmological and clinical examinationassessed by CTCAE v5.0

  Weekly (IVitC) or monthly (IAC) during treatment, at end of treatment (1 month after last injection), at 6, 12 and 24 months, yearly until 60 months

Study Arms (7)

Treatment 1a

ACTIVE COMPARATOR

IVitC melphalan (randomized) in case of vitreous relapse only

Drug: Melphalan

Treatment 1b

EXPERIMENTAL

IVitC topotecan (randomized) in case of vitreous relapse only

Drug: Topotecan

Treatment 2a

ACTIVE COMPARATOR

IAC melphalan (randomized) in case of retinal/diffuse subretinal relapse with no prior intra-arterial treatment

Drug: Melphalan

Treatment 2b

EXPERIMENTAL

IAC melphalan and topotecan (randomized) in case of retinal/diffuse subretinal relapse with no prior intra-arterial treatment

Drug: Topotecan; Drug: Melphalan

Treatment 2c

NO INTERVENTION

IAC melphalan and topotecan (randomized) in case of retinal/diffuse subretinal relapse with prior intra-arterial treatment

Treatment 3a

NO INTERVENTION

sequential administration of IVitC melphalan and IAC melphalan in case of combined vitreous and retinal/diffuse subretinal relapse, if no pretreatment with intra-arterial treatment

Treatment 3b

NO INTERVENTION

sequential administration of IVitC melphalan and IAC melphalan and topotecan, in case of combined vitreous and retinal/diffuse subretinal relapse, if prior pretreatment with intra-arterial treatment

Interventions

Topotecan DRUG

intravitreal or intra-arterial administration of topotecan

Also known as: hycamtin

Treatment 1b; Treatment 2b

Melphalan DRUG

intravitreal or intra-arterial administration of topotecan

Also known as: alkeran

Treatment 1a; Treatment 2a; Treatment 2b

Eligibility Criteria

• Age: 3 Months - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Eye with recurrent Rb clinically defined as one or the combination of the following:
• vitreous recurrence only
• retinal / diffuse subretinal relapse only not amenable to focal treatment such as thermotherapy, cryotherapy or plaque
• combined vitreous and retinal/diffuse subretinal relapse
• Minimally required interval between study entry and time of the last treatment: 2 months (with a monthly follow-up), except for small retinal / subretinal tumors treated focally, not related to the current relapse
• Photographic documentation of fundus at study entry
• Registration into the study and start of treatment must occur no later than 14 days after diagnosis of recurrence
• Mandatory ultrasound biomicroscopy (UBM) at 35 or 50 MHz in case of opaque media or insufficient pupillary dilatation for evaluation of the posterior chamber / pars plana
• Age ≥3 months and \< 11 years (10.99)
• Weight ≥5 kg (in case of IAC eligibility or sequential IVitC/IAC eligibility)
• Possibility of follow-up until at least 2 years after end of current relapse treatment
• Written informed consent by parents or legal representative before enrolment

You may not qualify if:

• Relapse with any uveal involvement and/or anterior chamber involvement
• Indication for another treatment option according to investigator's judgement
• Clinical/MRI signs of extraocular disease, including metastatic disease
• Inadequate organ function (in case of IAC or sequential IVitC / IAC eligibility):
• absolute neutrophils count \<0.5 G/l
• thrombocytes count \<100 G/l
• creatinine above normal value for age
• ALAT more than 2x above upper normal limit
• bilirubin above upper normal limit
• Other (simultaneous) malignancies
• Contraindication or known hypersensitivity to study drugs
• Severe concomitant diseases (e.g. immune deficiency syndrome)
• Current or recent (within 30 days prior to date of written informed consent) treatment with another investigational drug or participation in another interventional clinical trial

Sponsors & Collaborators

• Prof. Beck Popovic Maja: lead

Study Sites (1)

CHUV Lausanne University Hospital

Lausanne, 1011, Switzerland

Location

MeSH Terms

Conditions

Retinoblastoma

Interventions

Topotecan; Melphalan

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Retinal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases, Hereditary; Eye Diseases; Retinal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Maja Beck Popovic, Prof

  University of Lausanne Hospitals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of pediatric hematology oncology unit

Study Record Dates

• First Submitted: April 24, 2020
• First Posted: July 2, 2020
• Study Start: November 15, 2021
• Primary Completion: May 22, 2023
• Study Completion: May 22, 2023
• Last Updated: October 3, 2023

Record last verified: 2023-09

Locations

CH (1)