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A Phase II Study of Irinotecan + Temozolomide in Children With Recurrent Neuroblastoma

Phase 2
21 Years
Not Enrolling

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Trial Information

A Phase II Study of Irinotecan + Temozolomide in Children With Recurrent Neuroblastoma



- Determine the response rate in pediatric patients with relapsed neuroblastoma (NB)
treated with irinotecan hydrochloride and temozolomide.

- Determine the toxicities associated with irinotecan and temozolomide in patients
treated with this regimen.


- Evaluate the impact of p53 loss of function on response rate and event-free survival
from start of relapse therapy.

- Collect data for ongoing analyses of UGT1A1 polymorphisms in these patients.

- Collect and bank serum and nucleic acid specimen to facilitate future biomarker

- Evaluate the feasibility of collecting blood samples on a group wide basis for
assessment of changes in circulating markers of angiogenesis.

- Assess, preliminarily, the effects of irinotecan hydrochloride and temozolomide on
circulating markers of angiogenesis.

OUTLINE: This is a multicenter study.

Patients are stratified according to disease status (measurable disease [measured by
conventional CT scan and/or MRI] vs evaluable disease [tumor detected by conventional
morphologic analysis of bone marrow aspirate/biopsy AND/OR abnormal uptake at ≥ 1 site on
MIBG scan]).

Patients receive irinotecan hydrochloride IV over 1 hour on days 1-5 and 8-12 and oral
temozolomide on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence
of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 10 years.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Inclusion Criteria


- Histologically confirmed neuroblastoma AND/OR demonstration of tumor cells in the
bone marrow with increased urinary catecholamines at initial diagnosis

- Patients with elevated catecholamines only are not eligible

- Meets 1 of the following criteria:

- Recurrent disease following aggressive, multidrug, frontline chemotherapy,
defined as chemotherapy given with ≥ 2 agents, including an alkylating agent and
a platinum-containing compound

- Resistant/refractory disease during aggressive, multidrug, frontline

- Must meet 1 of the following criteria for documentation of disease:

- Unidimensionally measurable tumor ≥ 20 mm by MRI, CT scan, or x-ray OR ≥ 10 mm
by spiral CT scan within 4 weeks prior to study entry

- Patients with residual stable tumor upon completion of frontline therapy
must undergo biopsy to document presence of a viable neuroblastoma

- If the measurable target lesion was previously radiated, a biopsy must be
performed ≥ 4 weeks after radiation was completed AND the biopsy must
demonstrate viable neuroblastoma

- MIBG scan with positive uptake at ≥ 1 site within 4 weeks prior to study entry

- Patients with residual stable MIBG-positive lesions upon completion of
frontline therapy must undergo biopsy to document presence of viable

- If the patient has only 1 MIBG-positive lesion, and that lesion was
previously radiated, a biopsy must be performed ≥ 4 weeks after radiation
was completed AND the biopsy must demonstrate viable neuroblastoma

- Bone marrow with tumor cells on routine morphology (not by neuron-specific
enolase staining only) of bilateral aspirate and/or biopsy on 1 bone marrow
sample within 2 weeks prior to study entry

- No extensive marrow disease

- No myelodysplastic syndrome


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

- Life expectancy ≥ 8 weeks

- Absolute neutrophil count ≥ 750/mm^3

- Platelet count ≥ 75,000/mm^3 (transfusion independent)

- Hemoglobin ≥ 8.5 mg/dL (transfusion allowed)

- Creatinine adjusted according to age as follows:

- No greater than 0.4 mg/dL (≤ 5 months)

- No greater than 0.5 mg/dL (6 months -11 months)

- No greater than 0.6 mg/dL (1 year-23 months)

- No greater than 0.8 mg/dL (2 years-5 years)

- No greater than 1.0 mg/dL (6 years-9 years)

- No greater than 1.2 mg/dL (10 years-12 years)

- No greater than 1.4 mg/dL (13 years and over [female])

- No greater than 1.5 mg/dL (13 years to 15 years [male])

- No greater than 1.7 mg/dL (16 years and over [male]) OR

- Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min

- Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age

- ALT < 2.5 times ULN for age

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Seizure disorder allowed provided seizures are well controlled on non-EIAC medication

- No active diarrhea or uncontrolled infection

- No other malignancy, including secondary malignancy


- See Disease Characteristics

- Prior front-line therapy (e.g., surgery, chemotherapy, immunotherapy, radiotherapy,
or retinoids) allowed

- Recovered from prior therapy

- More than 4 weeks since prior radiation therapy to the site of any lesion that will
be identified as a target lesion to measure tumor response

- At least 2 weeks since prior myelosuppressive therapy (4 weeks for nitrosourea)

- At least 1 week since prior therapy with an antineoplastic biologic agent or retinoid

- At least 1 week since prior growth factors

- At least 1 week since prior and no other concurrent anticancer agents

- At least 1 week since prior and no concurrent enzyme-inducing anticonvulsants (EIAC),
including phenytoin, phenobarbital, valproic acid, or carbamazepine

- Concurrent gabapentin or levetiracetum allowed

- Concurrent palliative radiation therapy to sites not used to measure tumor response

- No prior allogeneic stem cell transplantation (SCT)

- Prior autologus SCT allowed

- No prior second-line chemotherapy for relapsed or refractory disease

- No concurrent immunomodulating agents

- Concurrent steroids for transfusion/infusion reactions or for treatment of edema
associated with CNS lesions allowed

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall response (complete and partial response)

Safety Issue:


Principal Investigator

Rochelle Bagatell, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Arizona


United States: Federal Government

Study ID:




Start Date:

April 2006

Completion Date:

Related Keywords:

  • Neuroblastoma
  • recurrent neuroblastoma
  • Neuroblastoma



Roswell Park Cancer Institute Buffalo, New York  14263
Children's Hospital of Philadelphia Philadelphia, Pennsylvania  19104
Mayo Clinic Cancer Center Rochester, Minnesota  55905
University of Chicago Cancer Research Center Chicago, Illinois  60637
Barbara Ann Karmanos Cancer Institute Detroit, Michigan  48201
Duke Comprehensive Cancer Center Durham, North Carolina  27710
Hurley Medical Center Flint, Michigan  48503
Medical City Dallas Hospital Dallas, Texas  75230
University of Texas Health Science Center at San Antonio San Antonio, Texas  78284-7811
Midwest Children's Cancer Center Milwaukee, Wisconsin  53226
CCOP - Kalamazoo Kalamazoo, Michigan  49007-3731
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center Farmington, Connecticut  06360-2875
Van Elslander Cancer Center at St. John Hospital and Medical Center Grosse Pointe Woods, Michigan  48236
Penn State Cancer Institute at Milton S. Hershey Medical Center Hershey, Pennsylvania  17033-0850
Vanderbilt-Ingram Cancer Center Nashville, Tennessee  37232-6838
Newark Beth Israel Medical Center Newark, New Jersey  07112
New York Medical College Valhalla, New York  10595
Holden Comprehensive Cancer Center at University of Iowa Iowa City, Iowa  52242-1002
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill Chapel Hill, North Carolina  27599-7570
CCOP - Scott and White Hospital Temple, Texas  76508
Cancer Research Center of Hawaii Honolulu, Hawaii  96813
Cleveland Clinic Taussig Cancer Center Cleveland, Ohio  44195
Sutter Cancer Center Sacramento, California  95816
Children's Hospital of Orange County Orange, California  92668
Children's National Medical Center Washington, District of Columbia  20010-2970
Children's Mercy Hospital Kansas City, Missouri  64108
Children's Hospital of Pittsburgh Pittsburgh, Pennsylvania  15213
Children's Hospital and Regional Medical Center - Seattle Seattle, Washington  98105
Nemours Children's Clinic Jacksonville, Florida  32207
Miami Children's Hospital Miami, Florida  33155-4069
All Children's Hospital St. Petersburg, Florida  33701
Children's Memorial Hospital - Chicago Chicago, Illinois  60614
Children's Hospital of New Orleans New Orleans, Louisiana  70118
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute Boston, Massachusetts  02115
St. Christopher's Hospital for Children Philadelphia, Pennsylvania  19134-1095
Driscoll Children's Hospital Corpus Christi, Texas  78466
Cook Children's Medical Center - Fort Worth Fort Worth, Texas  76104
Fletcher Allen Health Care - University Health Center Campus Burlington, Vermont  05401
Southern California Permanente Medical Group Downey, California  90242
Children's Hospital Central California Madera, California  93638-8762
Kosair Children's Hospital Louisville, Kentucky  40202-3830
Sunrise Hospital and Medical Center Las Vegas, Nevada  89109-2306
Children's Medical Center - Dayton Dayton, Ohio  45404
Palmetto Health South Carolina Cancer Center Columbia, South Carolina  29203
East Tennessee Children's Hospital Knoxville, Tennessee  37901
Covenant Children's Hospital Lubbock, Texas  79410
Children's Hospital of the King's Daughters Norfolk, Virginia  23507
Arizona Cancer Center at University of Arizona Health Sciences Center Tucson, Arizona  85724
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences Little Rock, Arkansas  72205
Blumenthal Cancer Center at Carolinas Medical Center Charlotte, North Carolina  28232-2861
Overlook Hospital Summit, New Jersey  07902-0220
Loma Linda University Cancer Institute at Loma Linda University Medical Center Loma Linda, California  92354
Jonathan Jaques Children's Cancer Center at Miller Children's Hospital Long Beach, California  90801
Kaiser Permanente Medical Center - Oakland Sacramento, California  95825
Lee Cancer Care of Lee Memorial Health System Fort Myers, Florida  33901
University of Florida Shands Cancer Center Gainesville, Florida  32610-0232
Florida Hospital Cancer Institute at Florida Hospital Orlando Orlando, Florida  32803-1273
Sacred Heart Cancer Center at Sacred Heart Hospital Pensacola, Florida  32504
St. Joseph's Cancer Institute at St. Joseph's Hospital Tampa, Florida  33607
Kaplan Cancer Center at St. Mary's Medical Center West Palm Beach, Florida  33407
Winship Cancer Institute of Emory University Atlanta, Georgia  30322
Blank Children's Hospital Des Moines, Iowa  50309
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital Baltimore, Maryland  21215
Floating Hospital for Children at Tufts - New England Medical Center Boston, Massachusetts  02111
Breslin Cancer Center at Ingham Regional Medical Center Lansing, Michigan  48910
Hackensack University Medical Center Cancer Center Hackensack, New Jersey  07601
Albert Einstein Cancer Center at Albert Einstein College of Medicine Bronx, New York  10461
Stony Brook University Cancer Center Stony Brook, New York  11794-8174
SUNY Upstate Medical University Hospital Syracuse, New York  13210
Presbyterian Cancer Center at Presbyterian Hospital Charlotte, North Carolina  28233-3549
Cincinnati Children's Hospital Medical Center Cincinnati, Ohio  45229-3039
Rainbow Babies and Children's Hospital Cleveland, Ohio  44106-5000
Hollings Cancer Center at Medical University of South Carolina Charleston, South Carolina  29425
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas Dallas, Texas  75390
Methodist Children's Hospital of South Texas San Antonio, Texas  78229-3993
Primary Children's Medical Center Salt Lake City, Utah  84113-1100
Providence Cancer Center at Sacred Heart Medical Center Spokane, Washington  99220-2555
St. Vincent Hospital Regional Cancer Center Green Bay, Wisconsin  54307-3508
James P. Wilmot Cancer Center at University of Rochester Medical Center Rochester, New York  14642
Childrens Hospital Los Angeles Los Angeles, California  90027
Children's Hospital and Research Center Oakland Oakland, California  94609
UCSF Helen Diller Family Comprehensive Cancer Center San Francisco, California  94115
Children's Hospital Center for Cancer and Blood Disorders Aurora, Colorado  80045
Alfred I. duPont Hospital for Children Wilmington, Delaware  19803
Mountain States Tumor Institute at St. Luke's Regional Medical Center Boise, Idaho  83712-6297
University of Illinois Cancer Center Chicago, Illinois  60612-7243
Indiana University Melvin and Bren Simon Cancer Center Indianapolis, Indiana  46202-5289
Lucille P. Markey Cancer Center at University of Kentucky Lexington, Kentucky  40536-0093
C.S. Mott Children's Hospital at University of Michigan Medical Center Ann Arbor, Michigan  48109-0286
Butterworth Hospital at Spectrum Health Grand Rapids, Michigan  49503-2560
Masonic Cancer Center at University of Minnesota Minneapolis, Minnesota  55455
Children's Hospitals and Clinics of Minnesota - Minneapolis Minneapolis, Minnesota  55404
University of Mississippi Cancer Clinic Jackson, Mississippi  39216-4505
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis St. Louis, Missouri  63110
Children's Hospital Omaha, Nebraska  68114-4113
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School New Brunswick, New Jersey  08903
University of New Mexico Cancer Center Albuquerque, New Mexico  87131-5636
Maimonides Cancer Center at Maimonides Medical Center Brooklyn, New York  11219
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center New York, New York  10032
Akron Children's Hospital Akron, Ohio  44308-1062
Nationwide Children's Hospital Columbus, Ohio  43205-2696
Geisinger Cancer Institute at Geisinger Health Danville, Pennsylvania  17822-0001
Dell Children's Medical Center of Central Texas Austin, Texas  78723
M. D. Anderson Cancer Center at University of Texas Houston, Texas  77030-4009
Virginia Commonwealth University Massey Cancer Center Richmond, Virginia  23298-0037
West Virginia University Health Sciences Center - Charleston Charleston, West Virginia  25302
Stanford Cancer Center Stanford, California  94305-5824
University of Miami Sylvester Comprehensive Cancer Center - Miami Miami, Florida  33136
Lehigh Valley Hospital - Muhlenberg Bethlehem, Pennsylvania  18017
Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham Birmingham, Alabama  35294