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A Phase 1 Dose Escalation Study of Reolysin, a Replication Competent Reovirus, in Pediatric Patients With Relapsed or Refractory Solid Tumors

Phase 1
3 Years
21 Years
Open (Enrolling)
Unspecified Childhood Solid Tumor, Protocol Specific

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Trial Information

A Phase 1 Dose Escalation Study of Reolysin, a Replication Competent Reovirus, in Pediatric Patients With Relapsed or Refractory Solid Tumors


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

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


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.

Inclusion Criteria:

- Diagnosis of relapsed or refractory solid tumors

- Must have had histologic verification of malignancy at original diagnosis or

- 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

- 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

- 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

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

- No concurrent acetaminophen

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum-tolerated dose (MTD), defined as the maximum dose at which fewer than one-third of patients experience DLT, graded using the NCI CTCAE version 4.0

Outcome Time Frame:

Up to 28 days

Safety Issue:


Principal Investigator

E. Anders Kolb

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

December 2010

Completion Date:

Related Keywords:

  • Unspecified Childhood Solid Tumor, Protocol Specific
  • Neoplasms



Baylor College of MedicineHouston, Texas  77030
Washington University School of MedicineSaint Louis, Missouri  63110
Midwest Children's Cancer CenterMilwaukee, Wisconsin  53226
Children's Hospital Los AngelesLos Angeles, California  90027-0700
Children's National Medical CenterWashington, District of Columbia  20010-2970
University of Oklahoma Health Sciences CenterOklahoma City, Oklahoma  73104
St. Jude Children's Research HospitalMemphis, Tennessee  38105-2794
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Montefiore Medical CenterBronx, New York  10467-2490
Children's Hospital of Pittsburgh of UPMCPittsburgh, Pennsylvania  15213
University of Alabama at BirminghamBirmingham, Alabama  35294-3300
Children's Hospital of AlabamaBirmingham, Alabama  35233
University of Texas Southwestern Medical CenterDallas, Texas  
Oregon Health and Science UniversityPortland, Oregon  97201
Seattle Children's HospitalSeattle, Washington  98105
Childrens Memorial HospitalChicago, Illinois  60614
Columbia University Medical CenterNew York, New York  10032
Cook Children's Medical CenterFort Worth, Texas  76104
University of Minnesota Medical Center-FairviewMinneapolis, Minnesota  55455
Children's Oncology GroupArcadia, California  91006-3776
C S Mott Children's HospitalAnn Arbor, Michigan  48109
Riley Hospital for ChildrenIndianapolis, Indiana  46202
Phoenix Childrens HospitalPhoenix, Arizona  85016
Childrens Hospital of Orange CountyOrange, California  92868-3874
Alfred I duPont Hospital for ChildrenWilmington, Delaware  19803
Nemours Children's Clinic - JacksonvilleJacksonville, Florida  32207-8426
University of California San Francisco Medical Center-ParnassusSan Francisco, California  94143