Advanced Intra-Ocular RetinoblastomaPhase 1NCT02116959

Alternating Systemic Chemotherapy and Intra-Arterial Melphalan (IAM) Chemotherapy in Children With Intra-Ocular Retinoblastoma

A Phase 1 study testing Melphalan, Carboplatin and Etoposide in people with Advanced Intra-Ocular Retinoblastoma and Retinoblastoma, run by University of California, San Francisco at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

The purpose of this study is to test the safety of the treatment combination of alternating standard chemotherapy and another (melphalan) chemotherapy at different interval schedules. Researchers want to find out what effects, good and/or bad, the treatment combination has on the patients and their retinoblastoma. Read more about this study

Who is it for?: Ages 3 months to 18 years
Conditions the study is for: Advanced Intra-Ocular Retinoblastoma, Retinoblastoma
What is being tested?: Melphalan, Carboplatin and Etoposide
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 6 participants
Where: 1 siteUnited States
Study dates: 23 Jul 2014to 25 May 2019
Phase: 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 3 months to 18 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

Age greater than or equal to 3 months up to 18 years.
Intraocular retinoblastoma not previously treated with systemic chemotherapy, radiation therapy, or IA therapy. Local retinal therapy such as laser photocoagulation and cryotherapy will be permitted.
Unilateral or bilateral retinoblastoma (RB) patients are eligible
Patients will be registered on study based on the local exam under anesthesia (EUA) done for diagnostic purposes prior to study entry. The EUA done at study entry should be done within 14 days prior to study entry
Patients may have had enucleation of one eye, as long as the remaining eye meets the eligibility criteria
Involved eye(s) must meet the definition for International Classification of Retinoblastoma

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For unilateral retinoblastoma (see Appendix 1 for International Classification of Retinoblastoma):
Group A eye that has failed local therapy
Group B eye that has failed local therapy
Group C eye that has failed local therapy
Group D eye
Group E eye that is not buphthalmic, is not planned for enucleation after first cycle of chemotherapy, and is in a child less than 1 year of age
For bilateral retinoblastoma (see Appendix 1 for International Classification of Retinoblastoma):
Group A and Group A eyes that have failed local therapy
Group A and Group B eyes that have failed local therapy
Group A and Group C eyes
Group A and Group D eyes
Group A and Group E eyes in which the Group E eye is not planned for enucleation after first cycle of chemotherapy
Group B and Group B eyes that have failed local therapy
Group B and Group C eyes
Group B and Group D eyes
Group B and Group E eyes in which the Group E eye is not planned for enucleation after first cycle of chemotherapy
Group C and Group C eyes
Group C and Group D eyes
Group C and Group E eyes even if early enucleation is planned for the Group E eye.
Group D and Group D eyes
Group D and Group E eyes even if early enucleation is planned for the Group E eye.
Group E and Group E eyes if at least one eye is not planned for enucleation.
Adequate Renal Function defined as: creatinine clearance or radioisotope Glomerular filtration rate (GFR) ³ 70 milliliter (mL)/min/1.73 m2 OR a serum creatinine based on age and gender derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the Center for Disease Control (CDC).
Adequate hematological function defined as:
Absolute Neutrophil Count > 1000/microliter
Platelet Count > 100,000/microliter
Adequate liver function defined as total bilirubin should be less than or equal to 1.5 x upper limit of normal (ULN) for age and serum glutamic-oxaloacetic transaminase (SGOT) / aspartate aminotransferase (AST) and serum glutamic-pyruvic transaminase (SGPT)
/ alanine aminotransferase (ALT) < 5 x upper limit of normal (ULN) for age
Adequate coagulation system as defined as an international normalized ratio (INR) of less than 1.4 and a partial thromboplastin time (PTT) of less than 34
Women and men of child-bearing potential must agree to use adequate contraception such as hormonal or barrier method of birth control or abstinence prior to study entry and for the duration of study participation. Should the subject or the subject's partner become pregnant or suspect pregnancy while on protocol therapy, the treating physician must be informed immediately.

Who cannot join

Any evidence of extraocular retinoblastoma clinically or by magnetic resonance imaging (MRI) of brain and orbits with and without gadolinium. MRI may be done within 21 days prior to study entry.
1. Evidence of systemic metastases on bilateral bone marrow, lumbar puncture, bone scan (or Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) scan), and/or any other additional tests done at study entry.
Patients who have previously been treated with chemotherapy (with the exception of second inclusion criteria) radiation therapy, or intra-arterial therapy.
Eyes with tumors that are amenable to local therapy with laser or cryotherapy without threat to vision
Any technical factor that would prohibit use of catheterization of the ophthalmic artery (e.g., small for age infant, untreatable allergy to contrast).
Abnormal cerebral vasculature noted on MR angiography that would increase the risk of the procedure, including but not limited to an incomplete Circle of Willis. Other abnormalities that are less severe than an incomplete Circle of Willis will be reviewed by the study chair in consultation with a neuro-interventional radiologist.

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Any serious ongoing condition, such as an untreated infection or organ dysfunction.
Patients receiving any medications or substances that are inhibitors or inducers of CYP450 enzyme(s) are ineligible.
Pregnant women are excluded from this study due to potential for teratogenic or abortifacient effects of therapy. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother breastfeeding should be discontinued upon start of protocol therapy.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of California, San Francisco
San Francisco, California, 94143

Other trials in United States

About this study

Official title: A Pilot Study Evaluating the Safety of Alternating Systemic Chemotherapy and Intra-Arterial Melphalan Chemotherapy in Children With Newly Diagnosed Advanced Intra-Ocular Retinoblastoma

Conditions: Advanced Intra-Ocular Retinoblastoma, Retinoblastoma
Being tested: Melphalan, Carboplatin, Etoposide, Vincristine
Keywords: Systemic, Chemotherapy, Melphalan
Medical subject headings: Retinoblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02116959
Study group	Role	What they receive
Cohort 1	Experimental	Patients will receive alternating treatments beginning with systemic chemotherapy then followed by intra-arterial (IA) therapy. Bilateral retinoblastoma patients will be in Cohort 1. For bilateral Bilateral retinoblastoma patients where one eye is stage A or B and the other eye is C, D, or E, only the higher stage eye (C, D, E) will be treated with IA chemotherapy unless the stage A or B eye is not amenable or has failed local therapy. Receives: Drug: Melphalan; Drug: Carboplatin; Drug: Etoposide; Drug: Vincristine
Cohort 2	Experimental	Patients will receive only intra-arterial (IA) therapy for more limited disease. Receives: Drug: Melphalan; Drug: Carboplatin; Drug: Etoposide; Drug: Vincristine

What is being measured

The primary outcome is the main question the study is designed to answer.

Adverse Event evaluation for newly diagnosed advanced retinoblastoma treated with melphalan therapy and systemic chemotherapy
Measured: Up to 2 years
Dose-Limiting Toxicity (DLT) and minimum tolerated dosing interval for combination IAM and carboplatin, vincristine, and etoposide (CEV).
Measured: Up to 2 years

Secondary outcomes (6)

Response rates after IAM combined with systemic CEV in patients with newly diagnosed advanced intraocular retinoblastoma
Measured: Up to 2 years
Ocular event free survival with the use of combination IAM therapy and systemic CEV in this patient population.
Measured: Up to 2 years
Visual outcomes using a standardized age based assessment
Measured: Up to 2 years
Salvage rate with triple IA therapy after failure of IA melphalan
Measured: Up to 2 years
Ocular event free survival for unilateral retinoblastoma with IA chemotherapy only for Group C or Group A/B that failed local therapy.
Measured: Up to 2 years
Visual outcomes using a standardized age based assessment.
Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Jul 201425 May 2019

First posted17 Apr 2014 (estimated)
Study start23 Jul 2014
Primary completion25 May 2019
Study completion25 May 2019

Why it stopped: Low accrual

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Advanced Intra-Ocular RetinoblastomaStudies of the same condition, open and under way.
More trials run by University of California, San FranciscoThe 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: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 6 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02116959
Sponsor's protocol ID: 13087
Other IDs: NCI-2015-01749
Status last verified: Apr 2020
First submitted: 18 Feb 2014
Last updated: 16 Apr 2020
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Study at a glance

From the registry record, last updated by the sponsor on 16 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Pilot Study Evaluating the Safety of Alternating Systemic Chemotherapy and Intra-Arterial Melphalan Chemotherapy in Children With Newly Diagnosed Advanced Intra-Ocular Retinoblastoma
ClinicalTrials.gov ID: NCT02116959
Acronym / sponsor ID: 13087
Conditions: Advanced Intra-Ocular Retinoblastoma, Retinoblastoma
Keywords: Systemic, Chemotherapy, Melphalan
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: Low accrual
Enrolment: 6 participants (actual)
Lead sponsor: University of California, San FranciscoUniversity, hospital or other
Study start: 23 Jul 2014 (actual)
Primary completion: 25 May 2019 (actual)
Study completion: 25 May 2019 (actual)
First posted: 17 Apr 2014 (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.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Cohort 1	Experimental	Drug: Melphalan, Drug: Carboplatin, Drug: Etoposide, Drug: VincristinePatients will receive alternating treatments beginning with systemic chemotherapy then followed by intra-arterial (IA) therapy. Bilateral retinoblastoma patients will be in Cohort 1. For bilateral Bilateral retinoblastoma patients where one eye is stage A or B and the other eye is C, D, or E, only the higher stage eye (C, D, E) will be treated with IA chemotherapy unless the stage A or B eye is not amenable or has failed local therapy.
Cohort 2	Experimental	Drug: Melphalan, Drug: Carboplatin, Drug: Etoposide, Drug: VincristinePatients will receive only intra-arterial (IA) therapy for more limited disease.

Who may qualify

Ages: 3 months to 18 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (36 listed)

Age greater than or equal to 3 months up to 18 years.
Intraocular retinoblastoma not previously treated with systemic chemotherapy, radiation therapy, or IA therapy. Local retinal therapy such as laser photocoagulation and cryotherapy will be permitted.
Unilateral or bilateral retinoblastoma (RB) patients are eligible
Patients will be registered on study based on the local exam under anesthesia (EUA) done for diagnostic purposes prior to study entry. The EUA done at study entry should be done within 14 days prior to study entry
Patients may have had enucleation of one eye, as long as the remaining eye meets the eligibility criteria

Key exclusion criteria (9 listed)

Any evidence of extraocular retinoblastoma clinically or by magnetic resonance imaging (MRI) of brain and orbits with and without gadolinium. MRI may be done within 21 days prior to study entry.
1. Evidence of systemic metastases on bilateral bone marrow, lumbar puncture, bone scan (or Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) scan), and/or any other additional tests done at study entry.
Patients who have previously been treated with chemotherapy (with the exception of second inclusion criteria) radiation therapy, or intra-arterial therapy.
Eyes with tumors that are amenable to local therapy with laser or cryotherapy without threat to vision
Any technical factor that would prohibit use of catheterization of the ophthalmic artery (e.g., small for age infant, untreatable allergy to contrast).

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
Melphalan	Drug	Cohort 1, Cohort 2
Carboplatin	Drug	Cohort 1, Cohort 2
Etoposide	Drug	Cohort 1, Cohort 2
Vincristine	Drug	Cohort 1, Cohort 2

Primary outcome

Adverse Event evaluation for newly diagnosed advanced retinoblastoma treated with melphalan therapy and systemic chemotherapy
Time frame: Up to 2 years
Dose-Limiting Toxicity (DLT) and minimum tolerated dosing interval for combination IAM and carboplatin, vincristine, and etoposide (CEV).
Time frame: Up to 2 years

6 secondary outcomes

Response rates after IAM combined with systemic CEV in patients with newly diagnosed advanced intraocular retinoblastoma
Time frame: Up to 2 years
Ocular event free survival with the use of combination IAM therapy and systemic CEV in this patient population.
Time frame: Up to 2 years
Visual outcomes using a standardized age based assessment
Time frame: Up to 2 years
Salvage rate with triple IA therapy after failure of IA melphalan
Time frame: Up to 2 years
Ocular event free survival for unilateral retinoblastoma with IA chemotherapy only for Group C or Group A/B that failed local therapy.
Time frame: Up to 2 years
Visual outcomes using a standardized age based assessment.
Time frame: Up to 2 years

Results and safety

The study was stopped early (reason given: Low accrual). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2020.
Individual participant dataSharing planned: No

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.

Anuradha Banerjee, MD principal investigator

University of California, San Francisco

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 36 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 16 Apr 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?

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?

The study was stopped early (reason given: Low accrual). 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?

Adverse Event evaluation for newly diagnosed advanced retinoblastoma treated with melphalan therapy and systemic chemotherapy (time frame: Up to 2 years). The study lists 2 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 NCT02116959.

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 16 Apr 2020.