Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

RATIONALE: Giving chemotherapy before an autologous stem cell transplant stops the growth of tumor cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and/or bone marrow and stored. More chemotherapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Radiation therapy uses high energy x-rays to kill tumor cells. Giving radiation therapy after combination chemotherapy and/or autologous stem cell transplant may kill any remaining tumor cells.

PURPOSE: This phase III trial is studying the side effects and how well giving combination chemotherapy together with autologous stem cell transplant and/or radiation therapy works in treating young patients with extraocular retinoblastoma..

Further Study Information

OBJECTIVES:

• 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.

• To estimate the response rate to the induction phase of the regimen.

• To evaluate the toxicities associated with this regimen.

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.

Eligibility 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 or CNS lesion consistent with trilateral retinoblastoma allowed provided the following:

• Unequivocal leptomeningeal disease is present on brain or spine by MRI scan

• Primary tumor is ≥ 2 cm in diameter, predominantly solid, and demonstrates enhancement on the post-Gadolinium images

• 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)

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2

• ANC ≥ 750/μL*

• Platelet count ≥ 75,000/μL* (transfusion independent)

• Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

• 0.4 mg/dL (1 month to < 6 months of age)

• 0.5 mg/dL (6 months to < 1 year of age)

• 0.6 mg/dL (1 years to < 2 years of age)

• 0.8 mg/dL (2 years to < 6 years of age)

• 1.0 mg/dL (6 years to < 10 years of age)

• 1.2 mg/dL (10 years to < 13 years of age)

• 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 years to < 16 years of age)

• 1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)

• 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

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

Trial Contact Information

Trial Lead Organizations/Sponsors

Children's Oncology Group

Ira Dunkel

Study Chair

Eric F. Grabowski

U.S.A.
Alabama
	Birmingham
	Children's Hospital of Alabama at University of Alabama at Birmingham
		Alyssa T Reddy	Ph: 205-934-0309
Arkansas
	Little Rock
	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
		David L Becton	Ph: 501-364-7373
California
	Arcadia
	Children's Oncology Group
		Ira J Dunkel	Ph: 212-639-2153
			Email: dunkeli@mskcc.org
	Downey
	Southern California Permanente Medical Group
		Robert M Cooper	Ph: 626-564-3455
	Los Angeles
	Childrens Hospital Los Angeles
		Rima F Jubran	Ph: 323-361-4110
	Palo Alto
	Lucile Packard Children's Hospital at Stanford University Medical Center
		Neyssa M Marina	Ph: 650-498-7061
			Email: clinicaltrials@med.stanford.edu
	San Francisco
	UCSF Helen Diller Family Comprehensive Cancer Center
		Katherine K Matthay	Ph: 877-827-3222
Colorado
	Aurora
	Children's Hospital Colorado Center for Cancer and Blood Disorders
		Kelly W Maloney	Ph: 720-777-6672
Connecticut
	Hartford
	Connecticut Children's Medical Center
		Michael S Isakoff	Ph: 860-545-9981
Delaware
	Wilmington
	Alfred I. duPont Hospital for Children
		Christopher N Frantz	Ph: 302-651-5755
District of Columbia
	Washington
	Children's National Medical Center
		Jeffrey S Dome	Ph: 202-884-2549
Florida
	Jacksonville
	Nemours Children's Clinic
		Eric S Sandler	Ph: 904-697-3529
	Miami
	University of Miami Sylvester Comprehensive Cancer Center - Miami
		Julio C Barredo	Ph: 866-574-5124
			Email: Sylvester@emergingmed.com
	Orlando
	Nemours Children's Clinic - Orlando
		Ramamoorthy Nagasubramanian	Ph: 407-650-7150
	Pensacola
	Nemours Children's Clinic - Pensacola
		Jeffrey H Schwartz	Ph: 904-697-3529
	Saint Petersburg
	All Children's Hospital
		Gregory A Hale	Ph: 727-767-2423
			Email: HamblinF@allkids.org
	Tampa
	St. Joseph's Children's Hospital of Tampa
		Hans-Christoph Rossbach	Ph: 800-882-4123
Georgia
	Atlanta
	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
		Howard M Katzenstein	Ph: 888-785-1112
Illinois
	Chicago
	Ann and Robert H. Lurie Children's Hospital of Chicago
		David O Walterhouse	Ph: 773-880-4562
	University of Illinois Cancer Center
		Mary L Schmidt	Ph: 312-355-3046
Indiana
	Indianapolis
	Riley's Children Cancer Center at Riley Hospital for Children
		Robert J Fallon	Ph: 317-274-2552
Iowa
	Iowa City
	Holden Comprehensive Cancer Center at University of Iowa
		Raymond Tannous	Ph: 800-237-1225
Kentucky
	Lexington
	University of Kentucky Chandler Medical Center
		Martha F Greenwood	Ph: 859-257-3379
Maryland
	Bethesda
	National Naval Medical Center
		Anne B Warwick	Ph: 301-319-2100
Mississippi
	Jackson
	University of Mississippi Cancer Clinic
		Gail C Megason	Ph: 601-815-6700
Missouri
	Kansas City
	Children's Mercy Hospital
		Maxine L Hetherington	Ph: 816-234-3265
Nevada
	Las Vegas
	CCOP - Nevada Cancer Research Foundation
		Jonathan Bernstein	Ph: 702-384-0013
New York
	New York
	Memorial Sloan-Kettering Cancer Center
		Peter G Steinherz	Ph: 212-639-7202
	Valhalla
	New York Medical College
		Mehmet F Ozkaynak	Ph: 914-594-3794
North Carolina
	Charlotte
	Blumenthal Cancer Center at Carolinas Medical Center
		Joel A Kaplan	Ph: 704-355-2884
	Presbyterian Cancer Center at Presbyterian Hospital
		Paulette C Bryant	Ph: 704-384-5369
	Durham
	Duke Cancer Institute
		Susan G Kreissman	Ph: 888-275-3853
Ohio
	Akron
	Akron Children's Hospital
		Steven J Kuerbitz	Ph: 330-543-3193
	Cincinnati
	Cincinnati Children's Hospital Medical Center
		John P Perentesis	Ph: 513-636-2799
	Cleveland
	Cleveland Clinic Taussig Cancer Center
		Tanya M Tekautz	Ph: 866-223-8100
	Seidman Cancer Center at University Hospitals/Case Medical Center
		Yousif (Joe) H Matloub	Ph: 216-844-5437
	Dayton
	Dayton Children's - Dayton
		Emmett H Broxson	Ph: 800-228-4055
Oklahoma
	Oklahoma City
	Oklahoma University Cancer Institute
		Rene Y McNall-Knapp	Ph: 405-271-4272
			Email: julie-traylor@ouhsc.edu
Pennsylvania
	Hershey
	Penn State Children's Hospital
		John F Kuttesch	Ph: 505-272-6972
			Email: CTO@hmc.psu.edu
	Philadelphia
	Children's Hospital of Philadelphia
		Kim E Nichols	Ph: 215-590-2810
	Pittsburgh
	Children's Hospital of Pittsburgh of UPMC
		Arthur K Ritchey	Ph: 412-692-5573
Tennessee
	Memphis
	St. Jude Children's Research Hospital
		Wayne L Furman	Ph: 901-595-4644
Texas
	Dallas
	Medical City Dallas Hospital
		Carl Lenarsky	Ph: 972-566-5588
	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
		Naomi J Winick	Ph: 214-648-7097
	Fort Worth
	Cook Children's Medical Center - Fort Worth
		Mary Meaghan P Granger	Ph: 682-885-2103
	Houston
	Dan L. Duncan Cancer Center at Baylor College of Medicine
		Lisa R Bomgaars	Ph: 713-798-1354
			Email: burton@bcm.edu
	Univeristy of Texas M.D. Anderson Cancer Center
		Cynthia E Herzog	Ph: 713-792-3245
	San Antonio
	Methodist Children's Hospital of South Texas
		Jaime Estrada	Ph: 210-575-7000
	University of Texas Health Science Center at San Antonio
		Anne-Marie R Langevin	Ph: 210-567-0653
			Email: che@uthscsa.edu
Virginia
	Richmond
	Virginia Commonwealth University Massey Cancer Center
		Kamar Godder	Ph: 804-628-1939
Wisconsin
	Green Bay
	St. Vincent Hospital Regional Cancer Center
		John R Hill	Ph: 920-433-8889
	Milwaukee
	Midwest Children's Cancer Center at Children's Hospital of Wisconsin
		Michael E Kelly	Ph: 414-805-4380
Argentina
	Buenos Aires
	Hospital de Pediatria Garrahan
		Guillermo L Chantada	Ph: (54-11) 4308-4300 Interno/s:1301 / 1302
Australia
New South Wales
	Sydney
	Children's Hospital at Westmead
		Geoffrey B McCowage	Ph: 61-2-9845 1400
Western Australia
	Perth
	Princess Margaret Hospital for Children
		Catherine H Cole	Ph: (08) 9340 8330
			Email: admin@childcancerresearch.com.au
Canada
Nova Scotia
	Halifax
	IWK Health Centre
		Margaret C Yhap	Ph: 902-470-8394
Quebec
	Montreal
	Hopital Sainte Justine
		Yvan Samson	Ph: 514-345-4931
Egypt
Cairo
	El Saida Zenab
	Children's Cancer Hospital
		Ira J Dunkel	Ph: (212) 639-7202

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00554788
Information obtained from ClinicalTrials.gov on November 20, 2012

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