Working… Menu

Intra-arterial Melphalan in Treating Younger Patients With Unilateral Retinoblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02097134
Recruitment Status : Active, not recruiting
First Posted : March 26, 2014
Results First Posted : June 26, 2018
Last Update Posted : September 22, 2020
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Unilateral Retinoblastoma Drug: Melphalan Not Applicable

Detailed Description:


I. 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.


I. 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.


I. To evaluate the effects of intra-arterial therapy on the histopathology of eyes enucleated for progression.


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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-institutional Feasibility Study of Intra-arterial Chemotherapy Given in the Ophthalmic Artery of Children With Retinoblastoma
Actual Study Start Date : April 16, 2014
Actual Primary Completion Date : June 30, 2017
Estimated Study Completion Date : September 30, 2021

Arm Intervention/treatment
Experimental: Treatment (melphalan)
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.
Drug: Melphalan
Given IA
Other Names:
  • Alanine Nitrogen Mustard
  • CB-3025
  • L-PAM
  • L-Phenylalanine Mustard
  • L-sarcolysin
  • L-Sarcolysin Phenylalanine mustard
  • L-Sarcolysine
  • Melphalanum
  • Phenylalanine Mustard
  • Phenylalanine nitrogen mustard
  • Sarcoclorin
  • Sarkolysin
  • WR-19813

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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 ]
    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.

  2. Probability of Ocular Salvage [ Time Frame: 2 years ]
    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.

  3. Rate of Metastases of Retinoblastoma [ Time Frame: Up to 2 years ]
    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

  4. Vision Acuity, Assessed According to the Amblyopia Treatment Study Visual Acuity Testing Protocol [ Time Frame: 1 year after therapy ]
    Estimated by the average visual acuity amongst patients evaluated with a 95% confidence interval.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   6 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02097134

Layout table for location information
United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
UCSF Medical Center-Parnassus
San Francisco, California, United States, 94143
UCSF Medical Center-Mission Bay
San Francisco, California, United States, 94158
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06520
United States, Florida
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States, 33136
United States, Georgia
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, United States, 77030
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Layout table for investigator information
Principal Investigator: Murali Chintagumpala Children's Oncology Group
  Study Documents (Full-Text)

Documents provided by Children's Oncology Group:
Layout table for additonal information
Responsible Party: Children's Oncology Group Identifier: NCT02097134    
Other Study ID Numbers: ARET12P1
NCI-2014-00618 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ARET12P1 ( Other Identifier: Childrens Oncology Group )
ARET12P1 ( Other Identifier: CTEP )
U10CA180886 ( U.S. NIH Grant/Contract )
U10CA098543 ( U.S. NIH Grant/Contract )
First Posted: March 26, 2014    Key Record Dates
Results First Posted: June 26, 2018
Last Update Posted: September 22, 2020
Last Verified: September 2020
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Retinal Neoplasms
Eye Neoplasms
Neoplasms by Site
Eye Diseases, Hereditary
Eye Diseases
Retinal Diseases
Nitrogen Mustard Compounds
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs