Unilateral RetinoblastomaPhase 1NCT02097134
Intra-arterial Melphalan in Treating Younger Patients With Unilateral Retinoblastoma
A Phase 1 study testing Melphalan in people with Unilateral Retinoblastoma, run by Children's Oncology Group at 12 sites in United States.
Trial summary
This pilot clinical trial studies whether unilateral group D retinoblastoma, or retinoblastoma affecting one eye that has spread to the inner jelly like part of the eye, can be treated with a new technique for delivering chemotherapy directly into the blood vessel that supplies the affected eye. Read more about this study
- Who is it for?
- Ages 6 months and older
- Conditions the study is for
- Unilateral Retinoblastoma
- What is being tested?
- Melphalan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 12 sitesUnited States
- Study dates
- 31 Oct 2014to 30 Sep 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 6 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Newly diagnosed patients with unilateral group D retinoblastoma
- Magnetic resonance imaging (MRI) (or computed tomography [CT] if MRI is not available) of the brain must be performed within 14 days prior to study entry
- Diagnostic examination under anesthesia (EUA) must be performed within 14 days prior to study entry
- Rapid central review confirmation of group D disease based on RetCam images from diagnostic EUA must be obtained before starting treatment
- Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2
- Patients must have a life expectancy of >= 8 weeks
Show all 19Show fewer
- Patients must have adequate renal function, defined as:
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or
- A serum creatinine based on age/gender as follows:
- 1 month to < 6 months: 0.4 mg/dL
- 6 months to < 1 year: 0.5 mg/dL
- 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 < 16 years: 1.5 mg/dL (male); 1.4 mg/dL (female)
- >= 16 years: 1.7 mg/dL (male); 1.4 mg/dL (female)
- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x upper limit of normal (ULN) for age
Who cannot join
- Patients with bilateral disease
- Unilateral retinoblastoma with group A, B, C, or E eyes
- Prior chemotherapy or radiation therapy for this disease (laser and cryotherapy are allowed and are not considered exclusion criteria)
- Clinical or neuroimaging evidence of extraocular disease or orbital optic nerve involvement
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Duke University Medical Center
Durham, North Carolina, 27710
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
M D Anderson Cancer Center
Houston, Texas, 77030
Children's Hospital Los Angeles
Los Angeles, California, 90027
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Yale University
New Haven, Connecticut, 06520
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
UCSF Medical Center-Parnassus
San Francisco, California, 94143
UCSF Medical Center-Mission Bay
San Francisco, California, 94158
About this study
Official title: A Multi-institutional Feasibility Study of Intra-arterial Chemotherapy Given in the Ophthalmic Artery of Children With Retinoblastoma
This pilot clinical trial studies whether unilateral group D retinoblastoma, or retinoblastoma affecting one eye that has spread to the inner jelly like part of the eye, can be treated with a new technique for delivering chemotherapy directly into the blood vessel that supplies the affected eye. This new technique is called intra-arterial injection. Giving melphalan via intra-arterial injection may make it less likely that children will need surgery to remove the eye and may reduce the amount of treatment side effects.
Read the detailed description
PRIMARY OBJECTIVES:
- To study the feasibility of delivering melphalan directly into the ophthalmic artery in children with newly diagnosed unilateral group D retinoblastoma, who would otherwise be considered for enucleation.
SECONDARY OBJECTIVES:
- To estimate the ocular salvage rate after treatment with intra-arterial melphalan in children with newly diagnosed unilateral retinoblastoma with group D disease.
II. To evaluate the toxicities and adverse events associated with delivering multiple doses of intra-arterial chemotherapy.
III. To evaluate vision outcomes in children treated with intra-arterial chemotherapy.
IV. To monitor the rate of the development of metastatic disease while on protocol therapy.
TERTIARY OBJECTIVES:
- To evaluate the effects of intra-arterial therapy on the histopathology of eyes enucleated for progression.
OUTLINE:
Patients receive melphalan intra-arterially (IA) on day 1. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then periodically for 2 years.
- Conditions
- Unilateral Retinoblastoma
- Being tested
- Melphalan
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MelphalanDrug
Also called Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard
Given IA
| Study group | Role | What they receive |
|---|---|---|
| Treatment (melphalan) | Experimental | Patients receive melphalan IA on day 1. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: Melphalan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Experiencing Feasibility Failure
Feasibility failure is defined as a) interventional radiologist is unable to access the ophthalmic artery for the 1st chemotherapy administration for any reason; b) patient develops central retinal artery occlusion after the 1st or 2nd course that does not reopen by the time the next injection is due; or c) the patient cannot receive all three treatments because of Common Terminology Criteria for Adverse Events (CTCAE) complications grade III or IV that are considered possibly, probably or likely related treatment.
Measured: Up to 4 months
Secondary outcomes (4)
Incidence of Grade 3 or Higher CTCAE Adverse Events Associated With Multiple Doses of IA Chemotherapy
The percentage of patients with at least 1 occurrence of grade 3 or higher CTCAE adverse experience will be provided. Ineligible patients or patients who do not receive any protocol therapy are excluded from reporting of adverse events.
Measured: Up to 30 days after completion of study treatment
Probability of Ocular Salvage
A patient will be considered an ocular-salvage success if enucleation because of disease progression or toxicity is not required during the 2 years following enrollment.
Measured: 2 years
Rate of Metastases of Retinoblastoma
The percentage of patients who experience metastases of retinoblastoma will be estimated. Ineligible patients or patients who do not receive any protocol therapy are excluded from this analysis
Measured: Up to 2 years
Vision Acuity, Assessed According to the Amblyopia Treatment Study Visual Acuity Testing Protocol
Estimated by the average visual acuity amongst patients evaluated with a 95% confidence interval.
Measured: 1 year after therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2014 (estimated)
- Study start31 Oct 2014
- Primary completion30 Jun 2017
- Study completion30 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Unilateral RetinoblastomaStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe 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
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Murali M Chintagumpala, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02097134
- Sponsor's protocol ID
- ARET12P1
- Other IDs
- NCI-2014-00618, ARET12P1, ARET12P1, ARET12P1, U10CA180886, U10CA098543
- Status last verified
- Oct 2023
- First submitted
- 25 Mar 2014
- Last updated
- 13 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-institutional Feasibility Study of Intra-arterial Chemotherapy Given in the Ophthalmic Artery of Children With Retinoblastoma
- ClinicalTrials.gov ID
- NCT02097134
- Acronym / sponsor ID
- ARET12P1
- Conditions
- Unilateral Retinoblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 31 Oct 2014 (actual)
- Primary completion
- 30 Jun 2017 (actual)
- Study completion
- 30 Sep 2023 (actual)
- First posted
- 26 Mar 2014 (estimated)
- Results
- Posted 26 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This pilot clinical trial studies whether unilateral group D retinoblastoma, or retinoblastoma affecting one eye that has spread to the inner jelly like part of the eye, can be treated with a new technique for delivering chemotherapy directly into the blood vessel that supplies the affected eye. This new technique is called intra-arterial injection. Giving melphalan via intra-arterial injection may make it less likely that children will need surgery to remove the eye and may reduce the amount of treatment side effects.
Detailed description
PRIMARY OBJECTIVES:
- To study the feasibility of delivering melphalan directly into the ophthalmic artery in children with newly diagnosed unilateral group D retinoblastoma, who would otherwise be considered for enucleation.
SECONDARY OBJECTIVES:
- To estimate the ocular salvage rate after treatment with intra-arterial melphalan in children with newly diagnosed unilateral retinoblastoma with group D disease.
II. To evaluate the toxicities and adverse events associated with delivering multiple doses of intra-arterial chemotherapy.
III. To evaluate vision outcomes in children treated with intra-arterial chemotherapy.
IV. To monitor the rate of the development of metastatic disease while on protocol therapy.
TERTIARY OBJECTIVES:
- To evaluate the effects of intra-arterial therapy on the histopathology of eyes enucleated for progression.
OUTLINE:
Patients receive melphalan intra-arterially (IA) on day 1. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then periodically for 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (melphalan) | Experimental | Drug: MelphalanPatients receive melphalan IA on day 1. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 6 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (19 listed)
- Newly diagnosed patients with unilateral group D retinoblastoma
- Magnetic resonance imaging (MRI) (or computed tomography [CT] if MRI is not available) of the brain must be performed within 14 days prior to study entry
- Diagnostic examination under anesthesia (EUA) must be performed within 14 days prior to study entry
- Rapid central review confirmation of group D disease based on RetCam images from diagnostic EUA must be obtained before starting treatment
- Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2
Key exclusion criteria (4 listed)
- Patients with bilateral disease
- Unilateral retinoblastoma with group A, B, C, or E eyes
- Prior chemotherapy or radiation therapy for this disease (laser and cryotherapy are allowed and are not considered exclusion criteria)
- Clinical or neuroimaging evidence of extraocular disease or orbital optic nerve involvement
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 |
|---|---|---|
| MelphalanAlso: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine MustardGiven IA | Drug | Treatment (melphalan) |
Primary outcome
Number of Patients Experiencing Feasibility Failure
Time frame: Up to 4 months
Feasibility failure is defined as a) interventional radiologist is unable to access the ophthalmic artery for the 1st chemotherapy administration for any reason; b) patient develops central retinal artery occlusion after the 1st or 2nd course that does not reopen by the time the next injection is due; or c) the patient cannot receive all three treatments because of Common Terminology Criteria for Adverse Events (CTCAE) complications grade III or IV that are considered possibly, probably or likely related treatment.
4 secondary outcomes
Incidence of Grade 3 or Higher CTCAE Adverse Events Associated With Multiple Doses of IA Chemotherapy
Time frame: Up to 30 days after completion of study treatment
Probability of Ocular Salvage
Time frame: 2 years
Rate of Metastases of Retinoblastoma
Time frame: Up to 2 years
Vision Acuity, Assessed According to the Amblyopia Treatment Study Visual Acuity Testing Protocol
Time frame: 1 year after therapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Murali M Chintagumpala principal investigator
Children's Oncology Group
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Melphalan in people with Unilateral Retinoblastoma, run by Children's Oncology Group at 12 sites 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 19 inclusion and 4 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: finished, as of the sponsor's last update on 13 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Patients Experiencing Feasibility Failure (time frame: Up to 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Oct 2023.