A Study of Intra-Ophthalmic Artery Topotecan Infusion for the Treatment of Retinoblastoma (IARB1)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:
NCT01466855
First received: October 19, 2011
Last updated: June 9, 2014
Last verified: June 2014
  Purpose

This study will test if giving topotecan directly into the blood vessel of the eye will improve the treatment of retinoblastoma. This method is referred to as "selective intra-ophthalmic artery chemotherapy" (SIOAC).

The goals of this study are:

  • To find out if topotecan is an effective treatment for retinoblastoma when delivered directly to the ophthalmic artery (SIOAC delivery)
  • To find out what kind of effects (good and bad) can be expected when topotecan is given by SIOAC
  • To assess visual pathway function before and after the study therapy
  • To learn more about the pharmacology (how your body handles the drug) of topotecan when delivered directly to the ophthalmic artery

Condition Intervention
Retinoblastoma
Drug: Intra-Ophthalmic Artery Topotecan Infusion

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Intra-Ophthalmic Artery Topotecan Infusion for the Treatment of Retinoblastoma

Resource links provided by NLM:


Further study details as provided by Children's Hospital Medical Center, Cincinnati:

Primary Outcome Measures:
  • 1-year event-free survival (event defined as the need for external beam radiation or enucleation) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Response rate of retinoblastoma to topotecan when administered directly into the ophthalmic artery. [ Time Frame: Up to 18 weeks ] [ Designated as safety issue: No ]
    EUA and retCAM imaging will be used to assess response rate.

  • Local (ocular) toxicities associated with the proposed regimen. Toxicities assessed using clinical examinations (EUA and Teller cards and Allan figures or Snellen visual acuity charts or other measures as appropriate for child's age.) [ Time Frame: Up to 12 months ] [ Designated as safety issue: Yes ]
    1. For non-verbal infants we will employ Teller cards or Reacts to Light (if vision is too poor for Teller cards)
    2. For pre-school age verbal toddlers/children we will employ LEA Symbols or HOTV, and possibly Allen figures
    3. For older children capable of reading an alphabet we will employ Snellen visual acuity charts. Standard methods to assess color vision will also be employed when feasible.

  • Patterns of response of retinoblastoma to topotecan when administered directly into the ophthalmic artery. [ Time Frame: Up to 18 weeks ] [ Designated as safety issue: No ]
    Physical examination of the tumors will be recorded at baseline and at every tumor assessment visit. Tumors will be classified as having Type I, II, III, IV, V or O response based on characteristic features identified during physical examination.


Secondary Outcome Measures:
  • Visual pathway function [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
    Evaluation of visual pathway function will be measured using visual acuity, electroretinogram, visual evoked potential, and functional magnetic resonance imaging.

  • Pharmacokinetics (Cmax and AUC) of topotecan when administered directly into the ophthalmic artery. [ Time Frame: Samples taken 15 and 60 minutes after topotecan administration on Day 1 of Cycle 1 (optional for patients) ] [ Designated as safety issue: No ]
  • Histologic findings in the eyes ultimately requiring enucleation. [ Time Frame: At time of enucleation, only if indicated ] [ Designated as safety issue: No ]
    Any eye requiring enucleation will be assessed for the presence or absence of 'high risk' features defined as scleral or massive choroidal invasion of viable tumor, anterior chamber involvement, invasion of the optic nerve posterior to the lamina cribrosa, ciliary body or iris invasion.


Estimated Enrollment: 36
Study Start Date: October 2011
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment of Retinoblastoma
Study of Intra-Ophthalmic Artery Topotecan infusion for the Treatment of Retinoblastoma.
Drug: Intra-Ophthalmic Artery Topotecan Infusion
Topotecan via intra-ophthalmic artery delivery infused over 30 minutes on Day 1 of every 21-day cycle.

  Eligibility

Ages Eligible for Study:   up to 15 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age: 15 years of age or younger
  2. Diagnosis: Patients with untreated Group C/D/E unilateral Retinoblastoma at presentation without an indication for immediate enucleation (neovascular glaucoma or orbital pain) (Stratum A), or patients with a history of bilateral retinoblastoma and recurrent and/or refractory intraocular retinoblastoma where chemotherapy, external beam radiation and/or enucleation remain the only known option for disease control (Stratum B).
  3. Therapeutic Options: Chemotherapy, External Beam Radiation therapy and/or Enucleation
  4. Lansky ≥ 50 for patients ≤ 10 years of age; Karnofsky ≥ 50 for patients > 10 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
  5. Prior Therapy: Stratum A: No prior therapy is allowed. Stratum B: 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. Prior radiation therapy is permitted.
  6. 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.
  7. Adequate Bone Marrow Function Defined as:

    • Peripheral absolute neutrophil count (ANC) greater than or equal to 750/uL
    • Platelet count greater than or equal to 75,000/uL (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to enrollment)
    • Hemoglobin greater than or equal to 8.0 gm/dL (may receive RBC transfusions)
  8. Adequate Renal Function Defined as:

    -Maximum serum creatinine based on age as follows: 1 to < 2 years- 0.6 mg/dL; 2 to < 6 years - 0.8 mg/dL; 6 to < 10 years- 1 mg/dL; 10 to < 13 years- 1.2 mg/dL; 13 to 15 years- 1.5 mg/dL for boys and 1.4 mg/dL for girls.

    OR

    Creatinine clearance or radioisotope GFR greater than or equal to 70ml/min/1.73 m2

  9. Adequate Liver Function Defined As:

    • Bilirubin (sum of conjugated + unconjugated) less than or equal to 1.5 x upper limit of normal (ULN) for age
    • SGPT (ALT) less than or equal to 5 x upper limit of normal (ULN) for age
    • Serum albumin greater than or equal to 2 g/dL
  10. Informed Consent: All patients and/or their parents or legal guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
  11. Patients of child-bearing potential must have a negative pregnancy test and agree to use an effective birth control method (abstinence is an acceptable form of birth control).

Exclusion Criteria:

  1. Extra-ocular retinoblastoma or retinoblastoma involving the anterior chamber
  2. Retinoblastoma that could otherwise be treated with laser therapy, cryotherapy, or plaque therapy only
  3. Structural brain abnormality
  4. Uncontrolled infection, defined as requiring intravenous antibiotics at the time of enrollment
  5. Concomitant Medications

    • Growth factors that support platelet or white cell number or function must not have been administered within 3 days prior to enrollment.
    • Patients who are currently receiving non-FDA approved drugs, or who have received a non-FDA approved drug within 7 days prior to enrollment, are ineligible.
    • Patients who are currently receiving other anti-cancer agents are ineligible.
  6. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01466855

Locations
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Investigators
Principal Investigator: James Geller, MD Children's Hospital Medical Center, Cincinnati
  More Information

No publications provided

Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT01466855     History of Changes
Other Study ID Numbers: IARB1
Study First Received: October 19, 2011
Last Updated: June 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Hospital Medical Center, Cincinnati:
Retinoblastoma

Additional relevant MeSH terms:
Retinoblastoma
Eye Diseases
Eye Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Retinal Diseases
Retinal Neoplasms
Topotecan
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 20, 2014