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

Basic Trial Information

Trial Description

Summary

This phase I trial is studying the side effects and the best dose of viral therapy in treating young patients with relapsed or refractory solid tumors. A virus called wild-type reovirus, which has been changed in a certain way, may be able to kill tumor cells without damaging normal cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving wild-type reovirus together with cyclophosphamide may kill more tumor cells.

Further Study Information

PRIMARY OBJECTIVES:

I. To estimate the maximum-tolerated dose (MTD) and/or recommended phase II dose of wild-type reovirus (Reolysin) in children with relapsed or refractory solid tumors.

II. To define and describe the toxicities of Reolysin in these patients. III. To define the toxicity and tolerability of combining Reolysin with oral cyclophosphamide in these patients.

IV. To characterize the pharmacokinetics (time course of viral clearance) of Reolysin in children with refractory cancer.

SECONDARY OBJECTIVES:

I. To define the antitumor activity of Reolysin within the confines of a phase I study.

II. To evaluate the development of neutralizing antibodies to Reolysin following intravenous administration of Reolysin alone and in combination with cyclophosphamide.

III. To assess the biologic activity of Reolysin.

OUTLINE: This is a dose-escalation study of wild-type reovirus (Reolysin).

Patients receive Reolysin IV over 60 minutes once daily on days 1-5. Some patients also receive oral cyclophosphamide on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for up to 1 year.

Eligibility Criteria

Inclusion Criteria:

• Diagnosis of relapsed or refractory solid tumors

• Must have had histologic verification of malignancy at original diagnosis or relapse

• Disease for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life

• No primary central nervous system (CNS) tumors or lymphomas

• Measurable or evaluable disease

• No known germline mutations affecting Ras activation (e.g., cardio-facial-cutaneous syndrome, Noonan syndrome, Costello syndrome)

• No known metastatic CNS disease

• Karnofsky performance status (PS) 50-100% for patients > 16 years of age OR Lansky PS 50-100% for patients ≤ 16 years of age

• Absolute neutrophil count (ANC) >= 1,000/mm^3

• Platelet count ≥ 100,000/mm³ (transfusion independent, defined as ≥ 7 days since platelet transfusion prior to enrollment)

• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min OR serum creatinine based on age and/or gender as follows:

• 0.8 mg/dL (3 to < 6 years of age)

• 1.0 mg/dL (6 to < 10 years of age)

• 1.2 mg/dL (10 to < 13 years of age)

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

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

• Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 times upper limit of normal (ULN)

• Alanine aminotransferase (ALT) =< 110 U/L (ULN for ALT is 45 U/L)

• Serum albumin ≥ 2 g/dL

• Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by gated radionuclide study

• Pulmonary function tests (PFTs), including diffusion capacity of carbon monoxide (DLCO), normal for patients with respiratory symptoms (e.g., dyspnea at rest, known requirement for supplemental oxygen)

• Full PFTs not required for patients without respiratory symptoms

• Seizure disorder allowed provided it is well controlled with anticonvulsants

• Nervous system disorders (NCI CTCAE v. 4) resulting from prior therapy must be ≤ grade 2

• Not pregnant or nursing

• Fertile patients must use effective contraception

• No uncontrolled infections

• No chronic diarrhea, urinary incontinence during the day or at night, or patients who are not completely toilet trained

• No household contacts (living with patient during the 4 weeks of treatment) who are pregnant, immunosuppressed, or infants < 3 months of age

• No patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

• No known HIV infection, hepatitis B or C, or any pre-existing infection

• Recovered from acute toxic effects of all prior anti-cancer chemotherapy and immunizations

• More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea)

• At least 14 days since prior long-acting growth factor (e.g., Neulasta) or ≥ 7 days since short-acting growth factor

• At least 7 days since prior biologic agent (anti-neoplastic agent)

• At least 16 weeks since prior immunotherapy (e.g., tumor vaccines)

• At least 3 half-lives since prior monoclonal antibody

• At least 2 weeks since prior palliative radiotherapy (small port)

• At least 24 weeks since prior total body irradiation, craniospinal radiotherapy, or ≥ 50% of radiotherapy to the pelvis

• At least 6 weeks since other prior substantial bone marrow radiation

• At least 12 weeks since prior stem cell transplant or infusion with no evidence of active graft-vs-host disease

• More than 7 days since prior viral immunizations, including influenza vaccine

• Patients may not receive any viral immunizations after enrolling on study and for ≥ 28 days after their last planned Reolysin infusion

• More than 7 days since prior corticosteroids, immune modulators, or antiviral therapy

• Intravenous immune globulin (IVIG) may not be given within 2 weeks of Reolysin administration

• No prior viral-based anti-neoplastic therapies

• No other concurrent investigational drugs

• No other concurrent anticancer agents including chemotherapy, radiotherapy, immunotherapy, or biologic therapy

• No concurrent cyclosporine, tacrolimus, or other agents to prevent either graft-versus-host disease after bone marrow transplant or organ rejection after transplant

• No concurrent corticosteroids (with the exception of hydrocortisone as a treatment for anaphylaxis), immune modulators, antiviral therapy, or IVIG

• No concurrent acetaminophen

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

E. Anders Kolb

Principal Investigator

U.S.A.
Alabama
	Birmingham
	Children's Hospital of Alabama at University of Alabama at Birmingham
		Joseph G Pressey	Ph: 205-934-0309
	UAB Comprehensive Cancer Center
		Joseph G Pressey	Ph: 205-934-0309
Arizona
	Phoenix
	Phoenix Children's Hospital
		Jessica Boklan	Ph: 602-546-0920
California
	Arcadia
	Children's Oncology Group
		E. Anders Kolb	Ph: 302-651-5567
			Email: eakolb@nemours.org
	Los Angeles
	Childrens Hospital Los Angeles
		Rajkumar Venkatramani	Ph: 323-361-4110
	Orange
	Children's Hospital of Orange County
		Violet Shen	Ph: 714-997-3000
	San Francisco
	UCSF Helen Diller Family Comprehensive Cancer Center
		Steven G DuBois	Ph: 877-827-3222
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
Illinois
	Chicago
	Ann and Robert H. Lurie Children's Hospital of Chicago
		Stewart Goldman	Ph: 773-880-4562
Indiana
	Indianapolis
	Riley's Children Cancer Center at Riley Hospital for Children
		James M Croop	Ph: 317-274-2552
Michigan
	Ann Arbor
	C.S. Mott Children's Hospital at University of Michigan Medical Center
		Rajen Mody	Ph: 800-865-1125
Minnesota
	Minneapolis
	Masonic Cancer Center at University of Minnesota
		Brenda J Weigel	Ph: 612-624-2620
Missouri
	Saint Louis
	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
		Robert J Hayashi	Ph: 800-600-3606
			Email: info@siteman.wustl.edu
New York
	Bronx
	Montefiore Medical Center
		Rosanna J Ricafort	Ph: 718-904-2730
			Email: aecc@aecom.yu.edu
	New York
	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
		Julia G Bender	Ph: 212-305-8615
Ohio
	Cincinnati
	Cincinnati Children's Hospital Medical Center
		Timothy P Cripe	Ph: 614-722-2708
Oklahoma
	Oklahoma City
	Oklahoma University Cancer Institute
		Rene Y McNall-Knapp	Ph: 405-271-4272
			Email: julie-traylor@ouhsc.edu
Oregon
	Portland
	Knight Cancer Institute at Oregon Health and Science University
		Linda C. Stork	Ph: 503-494-1080
			Email: trials@ohsu.edu
Pennsylvania
	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
	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
Washington
	Seattle
	Children's Hospital and Regional Medical Center - Seattle
		Julie R Park	Ph: 866-987-2000
Wisconsin
	Milwaukee
	Midwest Children's Cancer Center at Children's Hospital of Wisconsin
		Michael E Kelly	Ph: 414-805-4380
Canada
Ontario
	Toronto
	Hospital for Sick Children
		Sylvain Baruchel	Ph: 416-813-7654ext2027
			Email: jason.mcguire@sickkids.ca
Quebec
	Montreal
	Hopital Sainte Justine
		Yvan Samson	Ph: 514-345-4931

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01240538
Information obtained from ClinicalTrials.gov on April 01, 2013

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