Combination Chemotherapy and Cyclosporine Followed by Focal Therapy for Bilateral Retinoblastoma

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Brief Title

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)

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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

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

Secondary Outcome

 Toxicity during treatment

Condition

Retinoblastoma

Intervention

filgrastim

Study Arms / Comparison Groups

 CEV Chemo + Cyclosporine & Focal Therapy
Description:  Systemic carboplatin (28 mg/kg/dose), etoposide (12 mg/kg/dose) and vincristine sulfate (0.025 mg/kg/dose for the first cycle and 0.05 mg/kg/dose for subsequent cycles if first cycle well-tolerated) chemotherapy given with cyclosporin A (33 mg/kg/dose). Following 4-6 cycles CEV chemotherapy (depending on tumor stage) given every 3 weeks, focal laser therapy and/or cryosurgery are applied for tumor consolidation. Filgrastim is given after each chemotherapy cycle to prevent severe neutropenia.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

71

Start Date

June 2004

Completion Date

December 2021

Primary Completion Date

April 20, 2016

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
      

Gender

All

Ages

N/A - N/A

Accepts Healthy Volunteers

No

Contacts

Brenda L Gallie, MD, , 

Location Countries

Canada

Location Countries

Canada

Administrative Informations


NCT ID

NCT00110110

Organization ID

1000005587

Secondary IDs

HFSC-OCRN-RB-2003

Responsible Party

Principal Investigator

Study Sponsor

The Hospital for Sick Children

Collaborators

 Terry Fox Foundation

Study Sponsor

Brenda L Gallie, MD, Principal Investigator, The Hospital for Sick Children


Verification Date

October 2020