Intra-arterial Melphalan in Treating Younger Patients With Unilateral Retinoblastoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Children's Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT02097134
First received: March 25, 2014
Last updated: April 24, 2014
Last verified: April 2014
  Purpose

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 Intervention
Intraocular Retinoblastoma
Drug: melphalan

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Incidence of IA feasibility failure [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
    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:
  • Probability of ocular salvage [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Rate of metastases of retinoblastoma [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Incidence of grade 3 or higher CTCAE adverse events associated with multiple doses of IA chemotherapy [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    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.

  • Vision acuity, assessed according to the Amblyopia Treatment Study Visual Acuity Testing Protocol [ Time Frame: 1 year after therapy ] [ Designated as safety issue: No ]
    Estimated by the average visual acuity amongst patients evaluated with a 95% confidence interval.

  • Histopathology of eyes enucleated for progression [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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.

  • Catheter insertion complication rate [ Time Frame: Up to 48 hours after catheter insertion procedures ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 50
Study Start Date: April 2014
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • Alkeran
  • CB-3025
  • L-PAM
  • L-phenylalanine mustard
  • L-Sarcolysin

Detailed Description:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

TERTIARY OBJECTIVES:

I. 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.

  Eligibility

Ages Eligible for Study:   6 Months and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 (male); 1.4 (female) mg/dL
      • >= 16 years: 1.7 (male); 1.4 (female) mg/dL
  • 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02097134

Locations
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Murali M. Chintagumpala, MD    713-798-1354    burton@bcm.edu   
Principal Investigator: Murali M. Chintagumpala, MD         
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Murali Chintagumpala, MD Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT02097134     History of Changes
Other Study ID Numbers: ARET12P1, NCI-2014-00618, COG-ARET12P1, ARET12P1, U10CA098543, U10CA180886
Study First Received: March 25, 2014
Last Updated: April 24, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Retinoblastoma
Eye Diseases
Eye Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Retinal Diseases
Retinal Neoplasms
Melphalan
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014