A new treatment for advanced retinoblastoma in Africa
| ISRCTN | ISRCTN17864800 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN17864800 |
| IRAS number | LSHTM - 28454, NIMR/HQ/R.8a/Vol.IX/4804 |
| Secondary identifying numbers | Velux Stiftung 1824 |
- Submission date
- 09/10/2025
- Registration date
- 30/10/2025
- Last edited
- 10/10/2025
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
Retinoblastoma (Rb) affects children and is the commonest cause of death from eye cancer worldwide. Almost all these deaths occur in low /middle income countries (LMICs) where children are diagnosed late with advanced disease (spread beyond the eye) and where no/few trials have been conducted to decide how best to treat them.
Our aim is to significantly improve outcomes for children with advanced Rb by comparing a new chemotherapy treatment combination (topotecan and cyclophosphamide) with the standard three-drug combination (vincristine, etoposide and carboplatin) in Tanzania.
Who can participate?
Children presenting in Tanzania with Rb which has already spread beyond the eye and is therefore life threatening.
What does the study involve?
Participating children will be allocated by chance to a new chemotherapy treatment combination (topotecan and cyclophosphamide) OR the standard three-drug combination (vincristine, etoposide and carboplatin) in Tanzania.
What are the possible benefits and risks of participating?
Tumour spreading into the brain is the usual cause of death from Rb. Topotecan is one of the rare chemotherapy drugs that not only has activity against Rb but can reach into the brain (from the spine where it can be safely injected). There is a real and exciting possibility that this new combination will be a significant improvement in the treatment of this neglected group of children, and ultimately save lives.
All chemotherapy drugs carry risks of serious side effects and these will be closely monitored throughout the study.
Where is the study run from?
Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
When is the study starting and how long is it expected to run for.?
August 2023 to December 2028
Who is funding the study?
Velux Stiftung
Who is the main contact?
Dr Richard Bowman, richard.bowman@lshtm.ac.uk, richardbowman493@gmail.com
Contact information
Public, Scientific, Principal investigator
International Centre for Eye Health
London School of Hygiene and Tropical Medicine
London
WC1E 7HT
United Kingdom
 ORCID ID |
0000-0001-5422-4104 |
|---|---|
| Phone | +44 (0)7847921223 |
| richard.bowman@lshtm.ac.uk |
Study information
| Study design | Parallel-arm open-label individually randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment, Safety, Efficacy |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | The TopCAT trial – a randomised controlled trial investigating the survival benefit of adding topotecan/cyclophosphamide to standard therapy for advanced retinoblastoma in Tanzania |
| Study acronym | TopCAT |
| Study objectives | Primary Objective(s): To evaluate the effects of adding Topotecan to standard regimens on duration (from time of randomization) of survival of children with advanced retinoblastoma (Rb). Secondary Objective(s): 1. To determine the incidence of expected severe adverse events as the results of adding topotecan to standard regimens. 2. To determine the relapse of the disease after the patient has been treated with either Topotecan or standard treatment. 3. To determine the resistance of disease to the treatment. |
| Ethics approval(s) |
Approved 01/08/2023, London School Hygiene and Tropical Medicine, National Medical Research Institute of Tanzania (Keppel Street, London, WC1E 7HT, United Kingdom; +44 (0)7847921223; richardbowman493@gmail.com), ref: 28454 |
| Health condition(s) or problem(s) studied | Retinoblastoma |
| Intervention | Participating children will be allocated by chance to a new chemotherapy treatment combination (topotecan and cyclophosphamide) OR the standard three-drug combination (vincristine, etoposide and carboplatin) in Tanzania. Arm A: Standard Care Arm A patients receive a three-drug regimen administered on Day 1 of each cycle: Vincristine is given intravenously at a dose of 1.5 mg/m² body surface area (BSA), with a maximum dose of 2 mg. It is administered as a slow bolus over 2-3 minutes, diluted in not less than 10 ml of 0.9% sodium chloride (NaCl). There is a risk of extravasation with this medication. Etoposide is administered intravenously at 300 mg/m² BSA as a 4-hour infusion. It should be diluted to a concentration of 0.4 mg/ml in 0.9% NaCl. Rapid infusion must be avoided as it will lead to hypotensive crisis. Carboplatin is given intravenously at 600 mg/m² BSA as a 1-hour infusion, diluted to 0.5 mg/ml in either 5% dextrose (D5%) or dextrose in normal saline (DNS). Before each cycle, patients must meet specific hematological requirements: absolute neutrophil count (ANC) greater than 1, platelets greater than 100, and adequate levels of hemoglobin, renal function (renal profile), liver function tests (LFTs), and magnesium. Age-based dose modifications apply: patients less than 6 months old receive 50% of the dose for each drug, those 6 to 12 months old receive 75% of the dose, and patients over 12 months receive the full dose with no modification. Arm B: Experimental Arm Arm B patients receive an alternating regimen. They alternate between the standard VEC regimen (as described for Arm A) and an experimental regimen consisting of intravenous topotecan, intravenous cyclophosphamide, and intrathecal topotecan administered as follows: Topotecan is given intravenously at 1.5 mg/m² BSA daily on Days 1-5 of the cycle. It is administered as a 30-minute infusion, compatible with either 5% dextrose or 0.9% NaCl, with a final concentration of 25-50 mcg topotecan per ml. Cyclophosphamide is administered intravenously at 200 mg/m² BSA daily on Days 1-5 of the cycle as a 1-hour infusion, diluted to 0.4 mg/ml in 0.9% NaCl. Intrathecal topotecan is given on Day 1 of each cycle as a bolus injection. The dose is age-dependent: children over 3 years receive 0.4 mg, those between 2 and 3 years receive 0.32 mg, and children under 2 years receive 0.25 mg. The drug is diluted with preservative-free NaCl to a final volume of 3 ml. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Not Applicable |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Topotecan, cyclophosphamide, vincristine, etoposide, carboplatin |
| Primary outcome measure | Time to survival from randomization (months) |
| Secondary outcome measures | 1. Overall survival measured over 2-year follow up 2. Event-free survival. Events will be defined as: 2.1. Death (disease, treatment related or other) 2.2. Resistant disease (defined as unresectable tumors following neo-adjuvant chemotherapy) 2.3. Local, CNS or other distant relapses (defined as disease considered related to this presentation which returns after an initial response to treatment assessment confirmed a complete response) 2.4. Recurrent disease (defined as a new tumor deemed unrelated to the first disease, including disease beginning in the fellow eye or a tumor appearing at a new retinal site) 3. Treatment toxicity: 3.1. Bone marrow suppression: anaemia, (febrile) neutropenia, thrombocytopenia 3.2. Gastro-intestinal effects include vomiting, anorexia and resulting malnutrition, constipation 3.3. Etoposide infusion related hypotension 3.4. Hearing loss All harms that will be observed during the study will be reported including resistant disease, local CNS or distant relapse, as well as recurrent disease. Standard CTCAE grading will be used to assess and collect adverse events. All adverse events will be reported to NIMR per protocol. Patients with adverse events will be monitored with weekly lab until return to baseline. Standard prophylactic and supportive care protocols will be implemented, including use of antibiotics for fever and neutropenia during the care for patients with adverse events. Events and harms will be recorded at all points of the treatment programme and during and standardized follow-up procedure for 2 years post randomization. |
| Overall study start date | 01/08/2023 |
| Completion date | 01/12/2028 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 0 Years |
| Upper age limit | 17 Years |
| Sex | All |
| Target number of participants | 190 |
| Key inclusion criteria | Children presenting with stage 2 or stage 3 retinoblastoma in Tanzania |
| Key exclusion criteria | 1. Patients with pre-existing chronic illnesses which require treatment may impact on the ability to tolerate chemotherapy or radiotherapy 2. Patients with a history of prior treatment 3. Patients with suspected or documented life-threatening infections (should be established before enrolment) 4. Patients with stage 3 disease who are enucleated up front |
| Date of first enrolment | 01/12/2025 |
| Date of final enrolment | 01/12/2027 |
Locations
Countries of recruitment
- Tanzania
Study participating centres
Dar es Salaam
PO Box 65001
Tanzania
Mwanza
PO Box 1370
Tanzania
Moshi
PO Box 2240
Tanzania
Sponsor information
University/education
Keppel Street
London
WC1E 7HT
England
United Kingdom
| Website | http://www.lshtm.ac.uk/ |
|---|---|
"ROR" |
https://ror.org/00a0jsq62 |
Funders
Funder type
Charity
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Velux Foundation
- Location
- Switzerland
Results and Publications
| Intention to publish date | 01/06/2028 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | We are about to submit protocol for publication and will publish the results in international peer-reviewed journals |
| IPD sharing plan | The datasets generated during the study will be available on request from Richard Bowman (richardbowman493@gmail.com) |
Editorial Notes
09/10/2025: Study's existence confirmed by the National Institute for Medical Research (Tanzania).
