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
Last Update Posted : March 15, 2018
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. This may give children with unilateral retinoblastoma a lower chance of needing surgery to remove the eye and 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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
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
Study Start Date : April 2014
Actual Primary Completion Date : June 30, 2017
Estimated Study Completion Date : June 30, 2018

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. Incidence of IA 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. Catheter insertion complication rate [ Time Frame: Up to 48 hours after catheter insertion procedures ]
    Defined as (1) thrombosis of the femoral artery; (2) dissection of any artery; (3) hematoma at the site of insertion of 3 centimeters or more in diameter; (4) emboli cerebral; or (5) any embolus in the lower extremity that results in vascular insufficiency.

  2. Histopathology of eyes enucleated for progression [ Time Frame: Up to 5 years ]
    The proportion of enucleated eyes with various characteristics, such as viable vitreous seeds, invasion into the optic nerve, ischemic atrophy involving the outer retina and choroid, and extensive choroidal and outer retinal atrophy will be calculated, as well as the 95% confidence intervals.

  3. Incidence of grade 3 or higher CTCAE adverse events associated with multiple doses of IA chemotherapy [ Time Frame: Up to 5 years ]
    The occurrence of each grade 3 or higher CTCAE adverse experience will be recorded in each patient-cycle. The percentage of patients with each toxicity will be tabulated per cycle according to the methodology in place for the study progress report at the time.

  4. Probability of ocular salvage [ Time Frame: 2 years ]
  5. Rate of metastases of retinoblastoma [ Time Frame: Up to 2 years ]
  6. 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

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Ages Eligible for Study:   6 Months and older   (Child, Adult, Senior)
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

United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
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, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
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
Houston, Texas, United States, 77030
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Murali Chintagumpala, MD Children's Oncology Group

Responsible Party: Children's Oncology Group Identifier: NCT02097134     History of Changes
Other Study ID Numbers: ARET12P1
NCI-2014-00618 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ARET12P1 ( Other Identifier: Children's Oncology Group )
ARET12P1 ( Other Identifier: CTEP )
U10CA180886 ( U.S. NIH Grant/Contract )
U10CA098543 ( U.S. NIH Grant/Contract )
COG-ARET12P1 ( Other Identifier: Children's Oncology Group )
First Posted: March 26, 2014    Key Record Dates
Last Update Posted: March 15, 2018
Last Verified: March 2018

Additional relevant 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
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