Treatment Protocol for Non-Metastatic Unilateral Retinoblastoma

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).

• Combination Chemotherapy plus Intrathecal Topotecan (Combination product): Adjuvant chemotherapy with a reduced dose (compared to GALOP I protocol) of carboplatin
• Higher Dose Combination Chemotherapy plus Intrathecal Topotecan (Combination product): GALOP I-based systemic adjuvant therapy plus intrathecal topotecan
• Higher Dose Combination Chemotherapy plus Intrathecal Topotecan and Orbital Radiotherapy (Combination product): GALOP I-based systemic adjuvant therapy plus intrathecal topotecan and orbital radiotherapy (45 Gy) up to chiasm
• No Adjuvant Therapy (Other): Patients will not receive any adjuvant therapy after enucleation of the affected eye.

Primary outcomes

• Rate of extraocular relapses [3 years]: Number of participants experiencing extraocular relapse
• Evaluation of number of patients experiencing acute, chronic and fatal toxicities [5 years]: Number of participants experiencing treatment-related adverse effects and mortality as measured by CTCAE v4.0

Sex: All, ages: 0 Years to 6 Years

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