Treatment Protocol for Non-Metastatic Unilateral Retinoblastoma (RbGALOP2)

GALOP II Protocol for the Treatment of Unilateral Retinoblastoma

This protocol provides guidelines for the management of non-metastatic unilateral retinoblastoma and introduces an innovative adjuvant therapy for higher risk patients based upon the results of the Grupo de America Latina de Oncologia Pediatrica (GALOP) I study. Conservative therapy will be not protocolized.

Study Overview

• Status: Completed
• Conditions: Unilateral Retinoblastoma
• Intervention / Treatment: Other: No Adjuvant Therapy; Combination product: Combination Chemotherapy plus Intrathecal Topotecan; Combination product: Higher Dose Combination Chemotherapy plus Intrathecal Topotecan and Orbital Radiotherapy; Combination product: Higher Dose Combination Chemotherapy plus Intrathecal Topotecan

Detailed Description

Patients with non-metastatic retinoblastoma undergoing enucleation will be staged using the American Joint Committee on Cancer (AJCC), version 8, Tumor, Node, Metastasis (TNM)- H system and the International Retinoblastoma Staging System (IRSS). IRSS stage I patients recognized as higher risk will be assigned for adjuvant therapy. Those with standard risk will not receive adjuvant therapy after enucleation. Higher risk patients are defined as those with pathological retrolaminar optic nerve invasion and-or any degree of scleral invasion (pT3b, pT3c, pT3d). Based on the results of the GALOP I protocol, they will receive a reduced dose adjuvant chemotherapy regimen with 3 cycles of alternating cyclophosphamide, vincristine and idarubicin alternating with another 3 cycles of carboplatin and etoposide. Six doses of intrathecal topotecan will be given. Patients presenting with severe buphthalmia (cT3c-cT3e) will receive neo-adjuvant therapy with the same intensive regimen but including a higher dose of carboplatin as per GALOP I protocol plus intrathecal topotecan and secondary enucleation followed by adjuvant chemotherapy for a total of 8 cycles. Stage II patients (pT4) will receive the same adjuvant regimen plus orbital radiotherapy (45 cGy).

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • CF
    • Buenos Aires, CF, Argentina, C1245AAL
      • Hospital JP Garrahan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 6 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histological diagnosis of retinoblastoma confirmed at participating institutions
• Ophthalmological diagnosis of unilateral retinoblastoma in patients undergoing conservative therapy.
• No prior therapy for retinoblastoma
• Lansky Performance Scale greater or equal to 50
• Normal organ function in those patients assigned for chemotherapy
• Signed informed consent

Exclusion Criteria:

• Patients with unilateral retinoblastoma and germline mutations of the Rb1 gene or family history for retinoblastoma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Risk Patients; Patients with IRSS stage I, pT1, pT2 and pT3 stage will not receive adjuvant therapy	Other: No Adjuvant Therapy; Patients will not receive any adjuvant therapy after enucleation of the affected eye.
Experimental: Higher Risk Patients; Patients with IRSS stage I, pT3b, pT3c, pT3d will receive 6 cycles of adjuvant chemotherapy plus 6 doses of intrathecal topotecan	Combination product: Combination Chemotherapy plus Intrathecal Topotecan; Adjuvant chemotherapy with a reduced dose (compared to GALOP I protocol) of carboplatin
Experimental: Stage II Patients; Patients with Stage II (pT4) will receive 6 cycles of adjuvant chemotherapy plus 6 doses of intrathecal topotecan and orbital radiotherapy	Combination product: Higher Dose Combination Chemotherapy plus Intrathecal Topotecan and Orbital Radiotherapy; GALOP I-based systemic adjuvant therapy plus intrathecal topotecan and orbital radiotherapy (45 Gy) up to chiasm
Experimental: Patients with buphthalmus; Patients with buphthalmus (cT3c, cT3e) will receive 2 cycles of neo-adjuvant chemotherapy plus 6 doses of intrathecal topotecan followed by secondary enucleation and 6 cycles of adjuvant chemotherapy.	Combination product: Higher Dose Combination Chemotherapy plus Intrathecal Topotecan; GALOP I-based systemic adjuvant therapy plus intrathecal topotecan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of extraocular relapses	Number of participants experiencing extraocular relapse	3 years
Evaluation of number of patients experiencing acute, chronic and fatal toxicities	Number of participants experiencing treatment-related adverse effects and mortality as measured by CTCAE v4.0	5 years

Collaborators and Investigators

• Sponsor: Hospital JP Garrahan
• Collaborators: Hospital San Juan de Dios, Santiago

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Actual): January 31, 2023
• Study Completion (Actual): March 28, 2025

Study Registration Dates

• First Submitted: March 12, 2018
• First Submitted That Met QC Criteria: March 16, 2018
• First Posted (Actual): March 23, 2018

Study Record Updates

• Last Update Posted (Actual): April 13, 2025
• Last Update Submitted That Met QC Criteria: April 10, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Eye Diseases; Neoplasms, Glandular and Epithelial; Eye Diseases, Hereditary; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Eye Neoplasms; Retinal Diseases; Retinal Neoplasms; Retinoblastoma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Topotecan
• Other Study ID Numbers: 1031. Retinoblastoma GALOP 2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No