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Pilot Study of Topotecan/Vincristine With Subconjunctival Carboplatin for Patients With Bilateral Retinoblastoma (RELRB1)

Primary Purpose

Retinoblastoma

Status
Withdrawn
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
subtenon Carboplatin
Topotecan Hydrochloride
Vincristine
Filgrastim
Sponsored by
Children's Hospital Medical Center, Cincinnati
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Retinoblastoma

Eligibility Criteria

undefined - 10 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age: ≤ 10 years of age
  • Diagnosis: Patients must have a history of bilateral Retinoblastoma AND Recurrent/Refractory Intra-Ocular Retinoblastoma considered not amenable to cure with local therapies alone (photocoagulation with argon laser, cryotherapy, transpupillary thermotherapy, radioactive plaque therapy).
  • Therapeutic Options: Patient's disease status is one for which there are no known options proven to provide a high chance for ocular salvage or cure other than external beam radiation or enucleation.
  • Remaining visual function in target eye (s) is required
  • Life Expectancy of > 8 weeks
  • Lansky ≥ 50
  • Prior Therapy: Patients must have local relapsed/refractory disease after receiving standard upfront therapy involving at least one chemotherapeutic regimen. There is no limit to prior chemotherapeutic regimens permitted. Patients may have received previous intravenous carboplatin, but may not have received prior subtenon carboplatin or intravenous topotecan.

  • Patients must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study, as described below:

    • Myelosuppressive chemotherapy: patients must not have received myelosuppressive chemotherapy within 3 weeks of study enrollment
    • Biologic therapies: Patients must not have received biologic anti-cancer agents within one week of study enrollment
  • Radiation therapy: Four weeks must have elapsed since external beam radiation therapy, if given.

  • Adequate Bone Marrow Function Defined as:

    • Peripheral absolute neutrophil count (ANC) ≥ 750/µL
    • Platelet count ≥ 75,000/µL (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to enrollment)
    • Hemoglobin ≥ 8.0 gm/dL (may receive RBC transfusions)

  • Adequate Renal Function Defined as:

    • Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 OR threshold creatinine values based on age/gender derived from the Schwartz formula for estimating GFR

  • Adequate Liver Function Defined As:

    • Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
    • SGPT (ALT) ≤ 5 x upper limit of normal (ULN) for age
    • Serum albumin ≥ 2 g/dL

Exclusion Criteria:

  • Extra-ocular retinoblastoma
  • Asynchronous involvement of the contralateral eye, previously untreated
  • Uncontrolled infection at time of protocol entry

  • Concomitant Medications:

    • Growth factors that support platelet or white cell number or function must not have been administered within the past 3 days
    • Patients who are currently receiving investigational drugs, or who have received an investigational drug within the last 7 days, are ineligible
    • Patients who are currently receiving other anti-cancer agents are ineligible
  • Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

Sites / Locations

  • Cincinnati Children's Hospital Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Topotecan/Vincristine with subtenon Carboplatin

Arm Description

Outcomes

Primary Outcome Measures

To estimate the event-free survival, where an event is defined at the ocular level as the need for non-protocol therapy defined as additional non-protocol chemotherapy, external beam radiation, or enucleation.
To estimate the patterns of response, and response rate of locally refractory retinoblastoma to combination intravenous and peri-ocular chemotherapy.

Secondary Outcome Measures

To describe the toxicities associated with the proposed regimen.
To describe the histologic findings in the eyes ultimately requiring enucleation.
To describe the visual acuity of patients with advanced intraocular retinoblastoma before and after the proposed therapy.
To describe primary visual cortex function in patients with retinoblastoma via functional Magnetic Resonance Imaging (fMRI) technique both before and after the proposed therapy.

Full Information

First Posted
September 18, 2009
Last Updated
February 28, 2017
Sponsor
Children's Hospital Medical Center, Cincinnati
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1. Study Identification

Unique Protocol Identification Number
NCT00980551
Brief Title
Pilot Study of Topotecan/Vincristine With Subconjunctival Carboplatin for Patients With Bilateral Retinoblastoma
Acronym
RELRB1
Official Title
A Pilot Study of Intravenous Topotecan and Vincristine in Combination With Subconjunctival Carboplatin for Patients With a History of Bilateral Retinoblastoma and Refractory/Recurrent Intraocular Disease (IND# 104,942)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Withdrawn
Why Stopped
No enrollment and competing studies
Study Start Date
May 2010 (Actual)
Primary Completion Date
March 2012 (Actual)
Study Completion Date
March 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital Medical Center, Cincinnati

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The investigators are testing subtenon carboplatin in combination with vincristine and topotecan given by vein in the hopes of finding a drug combination that may be effective against retinoblastoma that has come back (recurrent) or is resistant to other treatment (refractory). The goals of this study are: To decide if the drug combination is a useful treatment for recurrent or refractory retinoblastoma To test the safety of the drug combination and to see what kind of effects (good and bad) can be expected from the drug combination To measure visual changes before and after the study therapy To use a special MRI scan to measure brain function involved in vision processing, both before and after the study therapy In this study, the investigators are also testing a new experimental way of giving carboplatin "subtenon carboplatin". The carboplatin will be given directly in the eye through a needle placed under the covering of the eye. This is to try to get more carboplatin to the retinoblastoma inside the eye.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Retinoblastoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Topotecan/Vincristine with subtenon Carboplatin
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
subtenon Carboplatin
Other Intervention Name(s)
Paraplatin
Intervention Description
Available in 50mg, 150mg, 450 mg, 600mg vials. It is provided as a premixed aqueous solution or lyophilized powder for injection given on day 1/week 10 (cycles 1-3).
Intervention Type
Drug
Intervention Name(s)
Topotecan Hydrochloride
Other Intervention Name(s)
Hycamtin
Intervention Description
Each vial contains topotecan hydrochloride equivalent to 4 mg of topotecan as free base. Given intravenously on days 1-5 of each week (cycles 1-6).
Intervention Type
Drug
Intervention Name(s)
Vincristine
Other Intervention Name(s)
Oncovin
Intervention Description
Each vial contains vincristine sulfate, 1 mg; mannitol, 100 mg; sterile water for injection; Acetic acid and sodium acetate are added for pH control. Given intravenously on day 1/week 1 (cycles 1-6).
Intervention Type
Drug
Intervention Name(s)
Filgrastim
Other Intervention Name(s)
Neupogen
Intervention Description
Supplied as a clear solution in 300 mcg/ml 1 ml or 1.6 ml vials and prefilled syringes containing 300mcg/0.5mL or 480mcg/0.8mL. Given intravenously on day 6 of each week (cycles 1-6).
Primary Outcome Measure Information:
Title
To estimate the event-free survival, where an event is defined at the ocular level as the need for non-protocol therapy defined as additional non-protocol chemotherapy, external beam radiation, or enucleation.
Time Frame
at 1 year
Title
To estimate the patterns of response, and response rate of locally refractory retinoblastoma to combination intravenous and peri-ocular chemotherapy.
Time Frame
at 1 yr
Secondary Outcome Measure Information:
Title
To describe the toxicities associated with the proposed regimen.
Time Frame
at 1 yr
Title
To describe the histologic findings in the eyes ultimately requiring enucleation.
Time Frame
at 1 yr
Title
To describe the visual acuity of patients with advanced intraocular retinoblastoma before and after the proposed therapy.
Time Frame
at 1 yr
Title
To describe primary visual cortex function in patients with retinoblastoma via functional Magnetic Resonance Imaging (fMRI) technique both before and after the proposed therapy.
Time Frame
at 1 yr

10. Eligibility

Sex
All
Maximum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age: ≤ 10 years of age Diagnosis: Patients must have a history of bilateral Retinoblastoma AND Recurrent/Refractory Intra-Ocular Retinoblastoma considered not amenable to cure with local therapies alone (photocoagulation with argon laser, cryotherapy, transpupillary thermotherapy, radioactive plaque therapy). Therapeutic Options: Patient's disease status is one for which there are no known options proven to provide a high chance for ocular salvage or cure other than external beam radiation or enucleation. Remaining visual function in target eye (s) is required Life Expectancy of > 8 weeks Lansky ≥ 50 Prior Therapy: Patients must have local relapsed/refractory disease after receiving standard upfront therapy involving at least one chemotherapeutic regimen. There is no limit to prior chemotherapeutic regimens permitted. Patients may have received previous intravenous carboplatin, but may not have received prior subtenon carboplatin or intravenous topotecan. Patients must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study, as described below: Myelosuppressive chemotherapy: patients must not have received myelosuppressive chemotherapy within 3 weeks of study enrollment Biologic therapies: Patients must not have received biologic anti-cancer agents within one week of study enrollment Radiation therapy: Four weeks must have elapsed since external beam radiation therapy, if given. Adequate Bone Marrow Function Defined as: Peripheral absolute neutrophil count (ANC) ≥ 750/µL Platelet count ≥ 75,000/µL (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to enrollment) Hemoglobin ≥ 8.0 gm/dL (may receive RBC transfusions) Adequate Renal Function Defined as: Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 OR threshold creatinine values based on age/gender derived from the Schwartz formula for estimating GFR Adequate Liver Function Defined As: Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age SGPT (ALT) ≤ 5 x upper limit of normal (ULN) for age Serum albumin ≥ 2 g/dL Exclusion Criteria: Extra-ocular retinoblastoma Asynchronous involvement of the contralateral eye, previously untreated Uncontrolled infection at time of protocol entry Concomitant Medications: Growth factors that support platelet or white cell number or function must not have been administered within the past 3 days Patients who are currently receiving investigational drugs, or who have received an investigational drug within the last 7 days, are ineligible Patients who are currently receiving other anti-cancer agents are ineligible Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James Geller, MD
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Pilot Study of Topotecan/Vincristine With Subconjunctival Carboplatin for Patients With Bilateral Retinoblastoma

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