Treatment Protocol for Non-Metastatic Unilateral Retinoblastoma

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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GALOP II Protocol for the Treatment of Unilateral Retinoblastoma

Conditions
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Unilateral Retinoblastoma

Intervention / Treatment
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* Combination Product: Combination Chemotherapy plus Intrathecal Topotecan
* Combination Product: Higher Dose Combination Chemotherapy plus Intrathecal Topotecan
* Combination Product: Higher Dose Combination Chemotherapy plus Intrathecal Topotecan and Orbital Radiotherapy
* Other: No Adjuvant Therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Risk Patients<br>Patients with IRSS stage I, pT1, pT2 and pT3 stage will not receive adjuvant therapy | Other: No Adjuvant Therapy<br>* Patients will not receive any adjuvant therapy after enucleation of the affected eye.<br>|
| Experimental: Higher Risk Patients<br>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<br>* Adjuvant chemotherapy with a reduced dose (compared to GALOP I protocol) of carboplatin<br>|
| Experimental: Stage II Patients<br>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<br>* GALOP I-based systemic adjuvant therapy plus intrathecal topotecan and orbital radiotherapy (45 Gy) up to chiasm<br>|
| Experimental: Patients with buphthalmus<br>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<br>* GALOP I-based systemic adjuvant therapy plus intrathecal topotecan<br>|

What is the study measuring?
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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 |