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

Retinoblastoma Clinical Trial

— IARB1  

Official title:

A Pilot Study of Intra-Ophthalmic Artery Topotecan Infusion for the Treatment of Retinoblastoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01466855
• Other study ID #: IARB1
• Status: Terminated
• Phase: Early Phase 1
• Start date: October 2011
• Est. completion date: October 2015

Study information

• Verified date: February 2017
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 36
• Est. completion date: October 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 15 Years

Eligibility

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.

Related Conditions & MeSH terms

• Retinoblastoma

Intervention

Drug:
• Intra-Ophthalmic Artery Topotecan Infusion
Topotecan via intra-ophthalmic artery delivery infused over 30 minutes on Day 1 of every 21-day cycle.

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1-year event-free survival (event defined as the need for external beam radiation or enucleation)		1 year
Primary	Response rate of retinoblastoma to topotecan when administered directly into the ophthalmic artery.	EUA and retCAM imaging will be used to assess response rate.	Up to 18 weeks
Primary	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.)	For non-verbal infants we will employ Teller cards or Reacts to Light (if vision is too poor for Teller cards); For pre-school age verbal toddlers/children we will employ LEA Symbols or HOTV, and possibly Allen figures; 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.	Up to 12 months
Primary	Patterns of response of retinoblastoma to topotecan when administered directly into the ophthalmic artery.	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.	Up to 18 weeks
Secondary	Visual pathway function	Evaluation of visual pathway function will be measured using visual acuity, electroretinogram, visual evoked potential, and functional magnetic resonance imaging.	Up to 12 months
Secondary	Pharmacokinetics (Cmax and AUC) of topotecan when administered directly into the ophthalmic artery.		Samples taken 15 and 60 minutes after topotecan administration on Day 1 of Cycle 1 (optional for patients)
Secondary	Histologic findings in the eyes ultimately requiring enucleation.	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.	At time of enucleation, only if indicated