Intra-arterial Chemotherapy for the Treatment of Intraocular Retinoblastoma

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01293539
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arm: 1
• Duration (Months): 65.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to show that chemotherapy delivered directly through the artery supplying the eye (ophthalmic artery) to patients with retinoblastoma is a safe and effective treatment alternative to conventional systemic chemotherapy, external beam radiation, and surgical removal of the eye.

Condition or Disease	Intervention/Treatment	Phase
Retinoblastoma	Drug: Melphalan hydrochloride	Phase 2

Detailed Description

Delivering the chemotherapeutic agent in the arterial system through the ophthalmic artery transforms the treatment of retinoblastoma from systemic chemotherapy to local chemotherapy. Administration of the drug directly to the targeted site thus avoids the complications and adverse events associated with toxicity from systemic, rather than local, chemotherapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Intra-arterial Chemotherapy for the Treatment of Intraocular Retinoblastoma
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Aug 1, 2016
• Actual Study Completion Date: Aug 1, 2016

Arms and Interventions

Arm

Intervention/Treatment

Other: Intraocular Retinoblastoma Patients Single group assignment of patients with intraocular retinoblastoma, unilateral or bilateral.

Drug: Melphalan hydrochloride; Drug administered intra-arterially (injection in the artery). Standard dose: 2.5mg (3-6 month old) 3.0 mg (6-12 month old) 4.0 mg (1-3 year old) 5.0 mg (>3 years old) Dose modification: decrease standard dose by 25% if there are signs of toxicity. Increase the dose by 25% if there is inadequate tumor response. Frequency: 2 treatment cycles at 3-4 week intervals, with a third treatment cycle administered if the tumor requires it. Dose not to exceed 0.5mg/kg, per treatment cycle.; Other Names: Alkeran

Outcome Measures

Primary Outcome Measures

1. Number of Patients Who Complete Therapy Without the Need for Additional Treatment Including Systemic Chemotherapy, External Beam Radiation, or Enucleation. [Within the first six months after the initial treatment.]

   The primary objective of this study is to show that intra-arterial delivery of the chemotherapeutic agent is successful in treating intraocular retinoblastoma, defined as avoiding systemic chemotherapy, external beam radiation, and enucleation.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients newborn to 18 years old.

• Patients with intraocular retinoblastoma, unilateral or bilateral, who would be treated either by systemic chemotherapy, EBR, or enucleation would be considered for this study.

Exclusion Criteria:

• Patients over the age of 18.

• Patients with small, localized intraocular Rb amenable to focal therapy (laser or cryotherapy).

• Patients with extraocular disease evident on MRI (extension into the optic nerve), massive choroidal/uveal invasion (grade IIC or IID per ARET0332) or disease outside the globe evident on MRI or physical examination.

• Documented hypercoagulable disorders or vasculopathies.

• Laboratory exclusion criteria: GFR < 60 mL/min/1.73 m2

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Johns Hopkins Hospital	Baltimore	Maryland	United States	21287

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Investigators

• Principal Investigator: Monica Pearl, M.D., Johns Hopkins University

Study Documents (Full-Text)

None provided.

More Information

Publications

• Abramson DH, Dunkel IJ, Brodie SE, Kim JW, Gobin YP. A phase I/II study of direct intraarterial (ophthalmic artery) chemotherapy with melphalan for intraocular retinoblastoma initial results. Ophthalmology. 2008 Aug;115(8):1398-404, 1404.e1. doi: 10.1016/j.ophtha.2007.12.014. Epub 2008 Mar 14.
• Abramson DH. Chemosurgery for retinoblastoma: what we know after 5 years. Arch Ophthalmol. 2011 Nov;129(11):1492-4. doi: 10.1001/archophthalmol.2011.354.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT01293539
• Other Study ID Numbers: J1071; NA_00040637
• First Posted: Feb 10, 2011
• Last Update Posted: Nov 27, 2018
• Last Verified: Nov 1, 2018

• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: Retinoblastoma; intra-arterial chemotherapy; angiography
• Additional relevant MeSH terms: Retinoblastoma; Melphalan

Study Results

Participant Flow

Arm/Group Title	Intra-arterial Chemotherapy
Arm/Group Description	IAC is offered to all patients with intraocular Rb who are deemed eligible after evaluation under anesthesia (EUA),with the exception of those few patients for whom focal modalities (i.e., laser or cryotherapy) would be effective.In cases of bilateral disease, both eyes would be treated sequentially during the same procedure utilizing the same femoral access site. Two cycles of IAC will be performed at 3 to 4 week intervals. Melphalan dosing: 3-6 mth-old, 2.5mg; 3-12 mth-old, 3mg; 1-3 yr-old, 4mg; >3 yr-old, 5mg. For those tumors that have shown appropriate response and are amenable to local therapies, then no additional IAC will be performed. If the tumors do not regress after 2 cycles, then a third cycle of IAC will be offered. Local therapies (laser, cryotherapy) will not be given during the EUAs conducted prior to each treatment session, but will be allowed after toxicity and response has been assessed 3-4 weeks after the final cycle of intra-arterial therapy.
Period Title: Overall Study
STARTED	10
COMPLETED	9
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Intra-arterial Chemotherapy
Arm/Group Description	IAC is offered to all patients with intraocular Rb who are deemed eligible after evaluation under anesthesia (EUA),with the exception of those few patients for whom focal modalities (i.e., laser or cryotherapy) would be effective.In cases of bilateral disease, both eyes would be treated sequentially during the same procedure utilizing the same femoral access site. Two cycles of IAC will be performed at 3 to 4 week intervals. Melphalan dosing: 3-6 mth-old, 2.5mg; 3-12 mth-old, 3mg; 1-3 yr-old, 4mg; >3 yr-old, 5mg. For those tumors that have shown appropriate response and are amenable to local therapies, then no additional IAC will be performed. If the tumors do not regress after 2 cycles, then a third cycle of IAC will be offered. Local therapies (laser, cryotherapy) will not be given during the EUAs conducted prior to each treatment session, but will be allowed after toxicity and response has been assessed 3-4 weeks after the final cycle of intra-arterial therapy.
Overall Participants	10
Age (Count of Participants)
<=18 years	10 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	7 70%
Male	3 30%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 30%
Not Hispanic or Latino	7 70%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 20%
White	7 70%
More than one race	0 0%
Unknown or Not Reported	1 10%
Region of Enrollment (Count of Participants)
United States	10 100%

Outcome Measures

1. Primary Outcome

Title	Number of Patients Who Complete Therapy Without the Need for Additional Treatment Including Systemic Chemotherapy, External Beam Radiation, or Enucleation.
Description	The primary objective of this study is to show that intra-arterial delivery of the chemotherapeutic agent is successful in treating intraocular retinoblastoma, defined as avoiding systemic chemotherapy, external beam radiation, and enucleation.
Time Frame	Within the first six months after the initial treatment.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intra-arterial Chemotherapy
Arm/Group Description	IAC is offered to all patients with intraocular Rb who are deemed eligible after evaluation under anesthesia (EUA),with the exception of those few patients for whom focal modalities (i.e., laser or cryotherapy) would be effective.In cases of bilateral disease, both eyes would be treated sequentially during the same procedure utilizing the same femoral access site. Two cycles of IAC will be performed at 3 to 4 week intervals. Melphalan dosing: 3-6 mth-old, 2.5mg; 3-12 mth-old, 3mg; 1-3 yr-old, 4mg; >3 yr-old, 5mg. For those tumors that have shown appropriate response and are amenable to local therapies, then no additional IAC will be performed. If the tumors do not regress after 2 cycles, then a third cycle of IAC will be offered. Local therapies (laser, cryotherapy) will not be given during the EUAs conducted prior to each treatment session, but will be allowed after toxicity and response has been assessed 3-4 weeks after the final cycle of intra-arterial therapy.
Measure Participants	10
Count of Participants [Participants]	10 100%

Adverse Events

Time Frame	4.5 years
Arm/Group Title	Intra-arterial Chemotherapy
Arm/Group Description	IAC is offered to all patients with intraocular Rb who are deemed eligible after evaluation under anesthesia (EUA),with the exception of those few patients for whom focal modalities (i.e., laser or cryotherapy) would be effective.In cases of bilateral disease, both eyes would be treated sequentially during the same procedure utilizing the same femoral access site. Two cycles of IAC will be performed at 3 to 4 week intervals. Melphalan dosing: 3-6 mth-old, 2.5mg; 3-12 mth-old, 3mg; 1-3 yr-old, 4mg; >3 yr-old, 5mg. For those tumors that have shown appropriate response and are amenable to local therapies, then no additional IAC will be performed. If the tumors do not regress after 2 cycles, then a third cycle of IAC will be offered. Local therapies (laser, cryotherapy) will not be given during the EUAs conducted prior to each treatment session, but will be allowed after toxicity and response has been assessed 3-4 weeks after the final cycle of intra-arterial therapy.
All Cause Mortality
	Intra-arterial Chemotherapy
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Intra-arterial Chemotherapy
	Affected / at Risk (%)	# Events
Total	3/10 (30%)
Eye disorders
Glaucoma	2/10 (20%)	2
Retinal vascular disorder	1/10 (10%)	1
Retinal vascular disorder	1/10 (10%)	1
Other (Not Including Serious) Adverse Events
	Intra-arterial Chemotherapy
	Affected / at Risk (%)	# Events
Total	6/10 (60%)
Eye disorders
Eyelid edema & erythema	1/10 (10%)	1
Eyelid function disorder	1/10 (10%)	1
Eyelid function disorder	1/10 (10%)	1
Eye pain	1/10 (10%)	1
Mild swelling	1/10 (10%)	1
Conjunctivitis	1/10 (10%)	1
Gastrointestinal disorders
Vomiting	1/10 (10%)	1
General disorders
Flu-like symptoms	1/10 (10%)	1
Fever	1/10 (10%)	1
Fever	1/10 (10%)	1
Infections and infestations
Ear infection	1/10 (10%)	1
Injury, poisoning and procedural complications
Injury - cut to lip during play	1/10 (10%)	1
Respiratory, thoracic and mediastinal disorders
Cough	2/10 (20%)	2
Cough	2/10 (20%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.