Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy, Autologous Stem Cell Transplant, and/or Radiation Therapy in Treating Young Patients With Extraocular Retinoblastoma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Active 10 and under NCI COG-ARET0321 ARET0321, NCT00554788

Objectives

1. To estimate the proportion of children with extraocular retinoblastoma who achieve long-term event-free survival after treatment with aggressive multimodality therapy compared to historical controls.
2. To estimate the response rate to the induction phase of the regimen.
3. To evaluate the toxicities associated with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed extraocular retinoblastoma, meeting 1 of the following criteria:
  • Stage 2 or 3 disease (regional extraocular disease)
  • Stage 4a disease (disseminated metastatic disease not involving the CNS, including extradural/dural disease without parenchymal or leptomeningeal disease)
  • Stage 4b disease (CNS disease, including trilateral retinoblastoma)



• Extraocular disease includes any of the following:
  • Orbital disease
  • Optic nerve involvement at the surgical margin
  • Regional nodal disease
  • Overt distant metastatic disease (at sites such as bone, bone marrow, liver, and/or the CNS)

Prior/Concurrent Therapy:

• No prior chemotherapy or radiotherapy for extraocular retinoblastoma
  • Prior chemotherapy and/or radiation therapy for intraocular retinoblastoma allowed
• No other concurrent anticancer chemotherapy, radiotherapy, or immunomodulating agents (including steroids)
  • Corticosteroid therapy is allowed only for treatment of increased intracranial pressure in patients with CNS tumors
  • Dexamethasone should not be prescribed as an anti-emetic

Patient Characteristics:

• ANC ≥ 750/μL*
• Platelet count ≥ 75,000/μL* (transfusion independent)
• Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST or ALT < 2.5 times ULN

 [Note: *Inadequate ANC and/or platelet count due to bone marrow metastatic disease allowed]

Expected Enrollment

Outcomes

Event-free survival

Response rate
Toxicity

Outline

This is a multicenter study. Patients are stratified according to disease stage (stage 2 or 3 [regional extraocular disease] vs stage 4a [disseminated metastatic disease not involving the CNS, including extradural/dural disease without parenchymal or leptomeningeal disease] vs stage 4b [CNS disease, including trilateral retinoblastoma]).

• Induction chemotherapy: Patients receive vincristine IV on days 0, 7, and 14, cisplatin IV over 6 hours on day 0, cyclophosphamide IV over 1 hour and etoposide IV over 1 hour on days 1 and 2, and filgrastim (G-CSF) subcutaneously (SC) beginning on day 3 and continuing until blood counts recover. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of induction chemotherapy, patients with stage 2 or 3 disease who have at least a partial response proceed to radiotherapy. Patients with stage 4a or 4b disease who have at least a partial response proceed to high-dose consolidation chemotherapy and autologous stem cell infusion.



• Stem cell harvesting (stage 4a or 4b disease only): Peripheral blood stem cells (preferred) or bone marrow cells are collected after at least 1 course of induction chemotherapy.



• High-dose consolidation chemotherapy (stage 4a or 4b disease only): Patients receive carboplatin IV over 4 hours on days -8 to -6 and thiotepa IV over 3 hours and etoposide IV over 3 hours on days -5 to -3.



• Autologous stem cell infusion (stage 4a or 4b disease only): Patients undergo autologous stem cell infusion on day 0. Patients then receive G-CSF SC beginning on day 1 and continuing until blood counts recover.



• Radiotherapy: Patients with stage 2 or 3 disease (orbital and/or regional involvement) undergo radiotherapy to sites that were initially involved beginning within 42 days after the start of course 4 of induction chemotherapy. Patients with stage 4a or 4b disease undergo radiotherapy to sites initially involved based on response beginning approximately 42 days after autologous stem cell infusion. Patients with stage 4a disease who achieve a complete response to induction chemotherapy or with less than 5 mm of residual tumor at the time of planned irradiation, or patients with stage 4b disease who achieve a complete response to induction chemotherapy do not undergo radiotherapy.

After completion of study therapy, patients are followed every 3 months for 1 year and then annually thereafter.

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Ira Dunkel, MD, Protocol chair		Ph: 212-639-2153; 800-525-2225 Email: dunkeli@mskcc.org
Eric Grabowski, MD, ScD, Protocol co-chair		Ph: 617-726-2737; 877-726-5130 Email: grabowski.eric@mgh.harvard.edu

U.S.A.
Connecticut
	Farmington
	Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
		Clinical Trials Office - Carole and Ray Neag Comprehensive Cancer Center	Ph:  800-579-7822
Florida
	St. Petersburg
	All Children's Hospital
		Jerry Barbosa	Ph:  727-767-4176
	West Palm Beach
	Kaplan Cancer Center at St. Mary's Medical Center
		Narayana Gowda	Ph:  561-844-6363
Georgia
	Atlanta
	Winship Cancer Institute of Emory University
		Howard Katzenstein	Ph:  404-785-0853
Indiana
	Indianapolis
	Indiana University Melvin and Bren Simon Cancer Center
		Clinical Trials Office - Indiana University Cancer Center	Ph:  317-274-2552
Kentucky
	Lexington
	Lucille P. Markey Cancer Center at University of Kentucky
		Clinical Trials Office - Markey Cancer Center at University of Kentucky Chandler Medical Center	Ph:  859-257-3379
Mississippi
	Jackson
	University of Mississippi Cancer Clinic
		Gail Megason	Ph:  601-984-5220
Missouri
	Kansas City
	Children's Mercy Hospital
		Maxine Hetherington	Ph:  816-234-3265
New York
	New York
	Memorial Sloan-Kettering Cancer Center
		Peter Steinherz	Ph:  212-639-7951
North Carolina
	Charlotte
	Blumenthal Cancer Center at Carolinas Medical Center
		Clinical Trials Office - Blumenthal Cancer Center at Carolinas Medical Center	Ph:  704-355-2884
Ohio
	Cincinnati
	Cincinnati Children's Hospital Medical Center
		Clinical Trials Office - Cincinnati Children's Hospital Medical Center	Ph:  513-636-0161
Oklahoma
	Oklahoma City
	Oklahoma University Cancer Institute
		Rene McNall-Knapp	Ph:  405-271-5311
Pennsylvania
	Hershey
	Penn State Cancer Institute at Milton S. Hershey Medical Center
		Clinical Trials Office - Penn State Cancer Institute at Milton S. Hershey Medical Center	Ph:  717-531-3779
			Email: CTO@hmc.psu.edu
	Philadelphia
	Children's Hospital of Philadelphia
		Peter Adamson	Ph:  215-590-6359
South Carolina
	Charleston
	Hollings Cancer Center at Medical University of South Carolina
		Clinical Trials Office - Hollings Cancer Center at Medical University of South Carolina	Ph:  843-792-9321
Texas
	Fort Worth
	Cook Children's Medical Center - Fort Worth
		Clinical Trials Office - Cook's Children's Medical Center	Ph:  682-885-2103
	Houston
	M. D. Anderson Cancer Center at University of Texas
		Clinical Trials Office - M. D. Anderson Cancer Center at the University of Texas	Ph:  713-792-3245
Australia
Western Australia
	Perth
	Princess Margaret Hospital for Children
		Catherine Cole	Ph:  011-6189340-8238
Canada
Quebec
	Montreal
	Montreal Children's Hospital at McGill University Health Center
		Sharon Abish	Ph:  514-412-4400x22219

Registry Information
Official Title		A Trial of Intensive Multi-Modality Therapy for Extra-Ocular Retinoblastoma
Trial Start Date		2008-02-04
Trial Completion Date		2009-07-13 (estimated)
Registered in ClinicalTrials.gov		NCT00554788
Date Submitted to PDQ		2007-10-16
Information Last Verified		2008-10-07
NCI Grant/Contract Number		CA98543