RetinoblastomaEarly Phase 1IARB1NCT01466855
A Study of Intra-Ophthalmic Artery Topotecan Infusion for the Treatment of Retinoblastoma
A Early Phase 1 study testing Intra-Ophthalmic Artery Topotecan Infusion in people with Retinoblastoma, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
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). Read more about this study
- Who is it for?
- Ages Up to 15 years
- Conditions the study is for
- Retinoblastoma
- What is being tested?
- Intra-Ophthalmic Artery Topotecan Infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2011to Oct 2015
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 15 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age: 15 years of age or younger
- 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).
- Therapeutic Options: Chemotherapy, External Beam Radiation therapy and/or Enucleation
- 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.
- 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.
- Patients must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study, as described below:
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- 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) 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)
- 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
- 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
- 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.
- 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).
Who cannot join
- Extra-ocular retinoblastoma or retinoblastoma involving the anterior chamber
- Retinoblastoma that could otherwise be treated with laser therapy, cryotherapy, or plaque therapy only
- Structural brain abnormality
- Uncontrolled infection, defined as requiring intravenous antibiotics at the time of enrollment
- Concomitant Medications
- Growth factors that support platelet or white cell number or function must not have been administered within 3 days prior to enrollment.
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- 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.
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
About this study
Official title: A Pilot Study of Intra-Ophthalmic Artery Topotecan Infusion for the Treatment of Retinoblastoma
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
- Conditions
- Retinoblastoma
- Being tested
- Intra-Ophthalmic Artery Topotecan Infusion
- Keywords
- Retinoblastoma
- Medical subject headings
- Retinoblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intra-Ophthalmic Artery Topotecan InfusionDrug
Topotecan via intra-ophthalmic artery delivery infused over 30 minutes on Day 1 of every 21-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Treatment of Retinoblastoma | Experimental | Study of Intra-Ophthalmic Artery Topotecan infusion for the Treatment of Retinoblastoma. Receives: Drug: Intra-Ophthalmic Artery Topotecan Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
1-year event-free survival (event defined as the need for external beam radiation or enucleation)
Measured: 1 year
Response rate of retinoblastoma to topotecan when administered directly into the ophthalmic artery.
EUA and retCAM imaging will be used to assess response rate.
Measured: Up to 18 weeks
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.
Measured: Up to 12 months
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.
Measured: Up to 18 weeks
Secondary outcomes (3)
Visual pathway function
Evaluation of visual pathway function will be measured using visual acuity, electroretinogram, visual evoked potential, and functional magnetic resonance imaging.
Measured: Up to 12 months
Pharmacokinetics (Cmax and AUC) of topotecan when administered directly into the ophthalmic artery.
Measured: Samples taken 15 and 60 minutes after topotecan administration on Day 1 of Cycle 1 (optional for patients)
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.
Measured: At time of enucleation, only if indicated
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2011 (estimated)
- Study startOct 2011
- Primary completionOct 2015
- Study completionOct 2015
Why it stopped: Competing studies
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for RetinoblastomaStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- James Geller, MD, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01466855
- Sponsor's protocol ID
- IARB1
- Acronym
- IARB1
- Status last verified
- Feb 2017
- First submitted
- 19 Oct 2011
- Last updated
- 14 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Abruzzo TA, Geller JI, Kimbrough DA, Michaels S, Correa ZM, Cornell K, Augsburger JJ. Adjunctive techniques for optimization of ocular hemodynamics in children undergoing ophthalmic artery infusion chemotherapy. J Neurointerv Surg. 2015 Oct;7(10):770-6. doi: 10.1136/neurintsurg-2014-011295. Epub 2014 Sep 1.
PubMed 25179634
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Intra-Ophthalmic Artery Topotecan Infusion for the Treatment of Retinoblastoma
- ClinicalTrials.gov ID
- NCT01466855
- Acronym / sponsor ID
- IARB1 / IARB1
- Conditions
- Retinoblastoma
- Keywords
- Retinoblastoma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Competing studies
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Study start
- Oct 2011
- Primary completion
- Oct 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 8 Nov 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment of Retinoblastoma | Experimental | Drug: Intra-Ophthalmic Artery Topotecan InfusionStudy of Intra-Ophthalmic Artery Topotecan infusion for the Treatment of Retinoblastoma. |
Who may qualify
- Ages
- Up to 15 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (23 listed)
- Age: 15 years of age or younger
- 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).
- Therapeutic Options: Chemotherapy, External Beam Radiation therapy and/or Enucleation
- 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.
- 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.
Key exclusion criteria (9 listed)
- Extra-ocular retinoblastoma or retinoblastoma involving the anterior chamber
- Retinoblastoma that could otherwise be treated with laser therapy, cryotherapy, or plaque therapy only
- Structural brain abnormality
- Uncontrolled infection, defined as requiring intravenous antibiotics at the time of enrollment
- Concomitant Medications
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intra-Ophthalmic Artery Topotecan InfusionTopotecan via intra-ophthalmic artery delivery infused over 30 minutes on Day 1 of every 21-day cycle. | Drug | Treatment of Retinoblastoma |
Primary outcome
1-year event-free survival (event defined as the need for external beam radiation or enucleation)
Time frame: 1 year
Response rate of retinoblastoma to topotecan when administered directly into the ophthalmic artery.
Time frame: Up to 18 weeks
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
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
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.
3 secondary outcomes
Visual pathway function
Time frame: Up to 12 months
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)
Histologic findings in the eyes ultimately requiring enucleation.
Time frame: At time of enucleation, only if indicated
Results and safety
The study was stopped early (reason given: Competing studies). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2020.
- Derived from this study: PubMed 25179634Abruzzo TA, Geller JI, Kimbrough DA, Michaels S, Correa ZM, Cornell K, Augsburger JJ. Adjunctive techniques for optimization of ocular hemodynamics in children undergoing ophthalmic artery infusion chemotherapy. J Neurointerv Surg. 2015 Oct;7(10):770-6. doi: 10.1136/neurintsurg-2014-011295. Epub 2014 Sep 1.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Geller, MD principal investigator
Children's Hospital Medical Center, Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Intra-Ophthalmic Artery Topotecan Infusion in people with Retinoblastoma, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Competing studies). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1-year event-free survival (event defined as the need for external beam radiation or enucleation) (time frame: 1 year). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01466855, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2020.