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Intra-arterial Melphalan in Treating Younger Patients With Unilateral Retinoblastoma

Primary Purpose

Unilateral Retinoblastoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Melphalan
Sponsored by
Children's Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Unilateral Retinoblastoma

Eligibility Criteria

6 Months - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Children's Hospital Los Angeles
  • UCSF Medical Center-Parnassus
  • UCSF Medical Center-Mission Bay
  • Yale University
  • University of Miami Miller School of Medicine-Sylvester Cancer Center
  • Children's Healthcare of Atlanta - Egleston
  • Dana-Farber Cancer Institute
  • Duke University Medical Center
  • Cincinnati Children's Hospital Medical Center
  • Children's Hospital of Philadelphia
  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (melphalan)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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
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.

Full Information

First Posted
March 25, 2014
Last Updated
October 6, 2023
Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02097134
Brief Title
Intra-arterial Melphalan in Treating Younger Patients With Unilateral Retinoblastoma
Official Title
A Multi-institutional Feasibility Study of Intra-arterial Chemotherapy Given in the Ophthalmic Artery of Children With Retinoblastoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
October 31, 2014 (Actual)
Primary Completion Date
June 30, 2017 (Actual)
Study Completion Date
September 30, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Unilateral Retinoblastoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (melphalan)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Melphalan
Other Intervention Name(s)
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
Intervention Description
Given IA
Primary Outcome Measure Information:
Title
Number of Patients Experiencing Feasibility Failure
Description
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.
Time Frame
Up to 4 months
Secondary Outcome Measure Information:
Title
Incidence of Grade 3 or Higher CTCAE Adverse Events Associated With Multiple Doses of IA Chemotherapy
Description
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.
Time Frame
Up to 30 days after completion of study treatment
Title
Probability of Ocular Salvage
Description
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.
Time Frame
2 years
Title
Rate of Metastases of Retinoblastoma
Description
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
Time Frame
Up to 2 years
Title
Vision Acuity, Assessed According to the Amblyopia Treatment Study Visual Acuity Testing Protocol
Description
Estimated by the average visual acuity amongst patients evaluated with a 95% confidence interval.
Time Frame
1 year after therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Accepts Healthy Volunteers
No
Eligibility 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Murali M Chintagumpala
Organizational Affiliation
Children's Oncology Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
UCSF Medical Center-Parnassus
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
UCSF Medical Center-Mission Bay
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
University of Miami Miller School of Medicine-Sylvester Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Children's Healthcare of Atlanta - Egleston
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

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Intra-arterial Melphalan in Treating Younger Patients With Unilateral Retinoblastoma

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