Clinical trial NCT00110110: Combination Chemotherapy and Cyclosporine Followed by Focal Therapy for Bilateral Retinoblastoma
Official title: Multicenter Phase II Study for International Intraocular Retinoblastoma Classification Groups B, C & D Tumors Treated With Carboplatin-Etoposide-Vincristine-Cyclosporine-Focal Therapy Multimodality Protocol (OCRN Multicenter RB 2003)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Retinoblastoma
Keywords: intraocular retinoblastoma
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
Collaborators: name: Terry Fox Foundation
First posted: 2005-05-04
Enrollment: 71
Sex: ALL
Minimum age (years): 30
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as carboplatin, etoposide, and vincristine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sometimes when chemotherapy is given, it does not stop the growth of tumor cells. The tumor is said to be resistant to chemotherapy. Giving cyclosporine together with chemotherapy may reduce drug resistance and allow the tumor cells to be killed. Cryotherapy kills tumor cells by freezing them. Laser therapy uses light to kill tumor cells. Giving combination chemotherapy together with cyclosporine followed by cryotherapy and/or laser therapy may be an effective treatment for retinoblastoma.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with cyclosporine followed by cryotherapy and/or laser therapy works in treating patients with newly diagnosed retinoblastoma in both eyes.

Detailed description: OBJECTIVES:

Primary

* Compare the efficacy of neoadjuvant high-dose carboplatin and etoposide, vincristine, and cyclosporine (CSA) followed by ophthalmic focal therapy comprising cryotherapy and/or laser therapy to historical world data of chemotherapy treatment without CSA, in terms of increasing the proportion of eyes that remain relapse free and do not require external beam radiotherapy and/or enucleation, in patients with newly diagnosed Group B, C, or D bilateral intraocular retinoblastoma.

Secondary

* Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive high-dose carboplatin IV over 30 minutes on day 1; vincristine IV over 5 minutes and high-dose etoposide IV over 25 minutes on day 2; cyclosporine IV over 1 hour before chemotherapy and then over 2 hours after chemotherapy on days 1 and 2, and filgrastim (G-CSF) subcutaneously once daily beginning on day 3 and continuing until day 16 or until blood counts recover. Treatment repeats every 21 days for a total of 3 courses for patients with Group B disease and a total of 6 courses for patients with Group C or D disease.

Patients undergo eye examination under anesthesia (EUA) at initial staging and then before each course of chemotherapy. Patients with small peripheral tumors in eyes without retinal detachment undergo minimal focal therapy (mainly cryotherapy) during EUA at initial staging and then after chemotherapy courses 1 and 2. At EUA after the third and subsequent courses of chemotherapy, patients with tumors that have sufficiently reduced in size undergo additional cryotherapy or laser therapy. After completion of chemotherapy, patients with any suspicious, active, or reactivated tumor undergo additional cryotherapy and/or laser therapy during EUA approximately every 4-8 weeks (or at longer intervals) for up to 5 years (as needed).

After completion of study chemotherapy, patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually for 1 year.

PROJECTED ACCRUAL: A total of 71 patients will be accrued for this study within 2.4 years.

Eligibility criteria: \>\>INCLUSION CRITERIA\<\<

DISEASE CHARACTERISTICS:

* Clinical diagnosis of bilateral intraocular retinoblastoma (RB)

  * International Intraocular Retinoblastoma Classification (IIRC) Group B, C, or D disease in 1 or both eyes
  * IIRC Group E disease in 1 eye allowed provided the eye was enucleated at diagnosis AND there is no extraocular RB in the enucleated eye by histologic confirmation AND there is IIRC Group B, C, or D disease in the remaining eye

PATIENT CHARACTERISTICS:

Age

* Over 30 days

Performance status

* Not specified

Life expectancy

* Not specified

Hematopoietic

* Not specified

Hepatic

* AST and ALT \< 2 times upper limit of normal (ULN)
* Conjugated and unconjugated bilirubin \< 2 times ULN

Renal

* Creatinine \< 1.5 times ULN
* Glomerular filtration rate (GFR) ≥ 100 mL/min\* NOTE: \*A 4-hour IV hydration is allowed if GFR is low due to poor hydration or transient dehydration

Other

* Meets 1 of the following auditory criteria:

  * Normal audiogram
  * At least normal responses to speech by audiogram
  * Documentation of hearing by acoustic emission test
  * Recording of evoked potentials by auditory brain stem response

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* Not specified

Endocrine therapy

* Not specified

Radiotherapy

* Not specified

Surgery

* See Disease Characteristics

  \>\>EXCLUSION CRITERIA\<\<
* IIRC Group A disease in 1 or both eyes
* unilateral RB
* extraocular or metastatic RB
* younger than 30 days
* Glomerular filtration rate (GFR) \< 100 mL/min

Primary outcomes:
measure: Comparing efficacy of study treatment with historic world data, in terms of increasing the proportion of eyes that remains relapse-free while avoiding external beam radiation and/or enucleation
timeFrame: 5 year follow-up per patient
Secondary outcomes:
measure: Toxicity during treatment
timeFrame: 5 year follow-up per patient
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: Children's and Women's Hospital of British Columbia
state: British Columbia
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: Montreal Children's Hospital at McGill University Health Center
state: Quebec
city: Santiago
country: Chile
facility: Hospital San Juan de Dios
city: Chennai
country: India
facility: Sankara Nethralaya Super Specialty Clinic
city: Singapore
country: Singapore
facility: Kandang Kerbau Women's and Children's Hospital
Study officials:
affiliation: The Hospital for Sick Children
name: Brenda L Gallie, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Hospital for Sick Children
name: Elise Heon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Hospital for Sick Children
name: Helen SL Chan, MD, BS
role: STUDY_CHAIR
References: