Clinical trial NCT00311584: Irinotecan and Temozolomide in Treating Young Patients With Recurrent Neuroblastoma
Official title: A Phase II Study of Irinotecan + Temozolomide in Children With Recurrent Neuroblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuroblastoma
Keywords: recurrent neuroblastoma
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-04-06
Enrollment: 59
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as irinotecan and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving irinotecan together with temozolomide works in treating young patients with recurrent neuroblastoma.

Detailed description: OBJECTIVES:

Primary

* 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.

Secondary

* 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 studies.
* 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.

Eligibility criteria: DISEASE CHARACTERISTICS:

* 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 chemotherapy
* Must meet 1 of the following criteria for documentation of disease:

  * Unidimensionally measurable tumor ≥ 20 mm by MRI (Magnetic Resonance Imaging), CT scan (Computed Tomography), 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 (metaiodobenzylguanidine scan, a radiopharmaceutical) 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 neuroblastoma
    * 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

PATIENT CHARACTERISTICS:

* 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

PRIOR CONCURRENT THERAPY:

* 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 levetiracetam allowed
* Concurrent palliative radiation therapy to sites not used to measure tumor response allowed
* No prior allogeneic stem cell transplantation (SCT)

  * Prior autologous 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

Primary outcomes:
measure: Overall Response - Complete Response (CR), Very Good Partial Response (VGPR) and Partial Response (PR)
timeFrame: up to 6 courses of therapy, or about 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
state: Alabama
city: Tucson
country: United States
facility: Arizona Cancer Center at University of Arizona Health Sciences Center
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
state: Arkansas
city: Downey
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Cancer Institute at Loma Linda University Medical Center
state: California
city: Long Beach
country: United States
facility: Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
state: California
city: Los Angeles
country: United States
facility: Childrens Hospital Los Angeles
state: California
city: Madera
country: United States
facility: Children's Hospital Central California
state: California
city: Oakland
country: United States
facility: Children's Hospital and Research Center Oakland
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Sacramento
country: United States
facility: Sutter Cancer Center
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente Medical Center - Oakland
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Aurora
country: United States
facility: Children's Hospital Center for Cancer and Blood Disorders
state: Colorado
city: Farmington
country: United States
facility: Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
state: Connecticut
city: Wilmington
country: United States
facility: Alfred I. duPont Hospital for Children
state: Delaware
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Fort Myers
country: United States
facility: Lee Cancer Care of Lee Memorial Health System
state: Florida
city: Gainesville
country: United States
facility: University of Florida Shands Cancer Center
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center - Miami
state: Florida
city: Miami
country: United States
facility: Miami Children's Hospital
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute at Florida Hospital Orlando
state: Florida
city: Pensacola
country: United States
facility: Sacred Heart Cancer Center at Sacred Heart Hospital
state: Florida
city: St. Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Tampa
country: United States
facility: St. Joseph's Cancer Institute at St. Joseph's Hospital
state: Florida
city: West Palm Beach
country: United States
facility: Kaplan Cancer Center at St. Mary's Medical Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Honolulu
country: United States
facility: Cancer Research Center of Hawaii
state: Hawaii
city: Boise
country: United States
facility: Mountain States Tumor Institute at St. Luke's Regional Medical Center
state: Idaho
city: Chicago
country: United States
facility: University of Illinois Cancer Center
state: Illinois
city: Chicago
country: United States
facility: Children's Memorial Hospital - Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Des Moines
country: United States
facility: Blank Children's Hospital
state: Iowa
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
city: Lexington
country: United States
facility: Lucille P. Markey Cancer Center at University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: Kosair Children's Hospital
state: Kentucky
city: New Orleans
country: United States
facility: Children's Hospital of New Orleans
state: Louisiana
city: Baltimore
country: United States
facility: Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
state: Maryland
city: Boston
country: United States
facility: Floating Hospital for Children at Tufts - New England Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: C.S. Mott Children's Hospital at University of Michigan Medical Center
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Butterworth Hospital at Spectrum Health
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: Van Elslander Cancer Center at St. John Hospital and Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: CCOP - Kalamazoo
state: Michigan
city: Lansing
country: United States
facility: Breslin Cancer Center at Ingham Regional Medical Center
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: Masonic Cancer Center at University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Cancer Clinic
state: Mississippi
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: St. Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: Omaha
country: United States
facility: Children's Hospital
state: Nebraska
city: Las Vegas
country: United States
facility: Sunrise Hospital and Medical Center
state: Nevada
city: Hackensack
country: United States
facility: Hackensack University Medical Center Cancer Center
state: New Jersey
city: Morristown
country: United States
facility: Overlook Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Bronx
country: United States
facility: Albert Einstein Cancer Center at Albert Einstein College of Medicine
state: New York
city: Brooklyn
country: United States
facility: Maimonides Cancer Center at Maimonides Medical Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Cancer Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Blumenthal Cancer Center at Carolinas Medical Center
state: North Carolina
city: Charlotte
country: United States
facility: Presbyterian Cancer Center at Presbyterian Hospital
state: North Carolina
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Dayton
country: United States
facility: Children's Medical Center - Dayton
state: Ohio
city: Bethlehem
country: United States
facility: Lehigh Valley Hospital - Muhlenberg
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Cancer Institute at Geisinger Health
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Hollings Cancer Center at Medical University of South Carolina
state: South Carolina
city: Columbia
country: United States
facility: Palmetto Health South Carolina Cancer Center
state: South Carolina
city: Knoxville
country: United States
facility: East Tennessee Children's Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Austin
country: United States
facility: Dell Children's Medical Center of Central Texas
state: Texas
city: Corpus Christi
country: United States
facility: Driscoll Children's Hospital
state: Texas
city: Dallas
country: United States
facility: Medical City Dallas Hospital
state: Texas
city: Dallas
country: United States
facility: Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center - Fort Worth
state: Texas
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
city: Lubbock
country: United States
facility: Covenant Children's Hospital
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: San Antonio
country: United States
facility: Methodist Children's Hospital of South Texas
state: Texas
city: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Medical Center
state: Utah
city: Burlington
country: United States
facility: Fletcher Allen Health Care - University Health Center Campus
state: Vermont
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughters
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Massey Cancer Center
state: Virginia
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
city: Spokane
country: United States
facility: Providence Cancer Center at Sacred Heart Medical Center
state: Washington
city: Charleston
country: United States
facility: West Virginia University Health Sciences Center - Charleston
state: West Virginia
city: Green Bay
country: United States
facility: St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Midwest Children's Cancer Center
state: Wisconsin
city: Newcastle
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Institute for Cancer Research at Westmead Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Royal Children's Hospital
state: Queensland
city: Parkville
country: Australia
facility: Royal Children's Hospital
state: Victoria
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: Children's & Women's Hospital of British Columbia
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster Children's Hospital at Hamilton Health Sciences
state: Ontario
city: London
country: Canada
facility: Children's Hospital of Western Ontario
state: Ontario
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: Montreal Children's Hospital at McGill University Health Center
state: Quebec
city: Montreal
country: Canada
facility: Hopital Sainte Justine
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre at Pasqua Hospital
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre at the University of Saskatchewan
state: Saskatchewan
city: Quebec
country: Canada
facility: Centre Hospitalier Universitaire de Quebec
Study officials:
affiliation: University of Arizona
name: Rochelle Bagatell, MD
role: STUDY_CHAIR
affiliation: Floating Hospital for Children at Tufts - New England Medical Center
name: Cynthia S. Kretschmar, MD
role: STUDY_CHAIR
References:
citation: Bagatell R, London WB, Wagner LM, Voss SD, Stewart CF, Maris JM, Kretschmar C, Cohn SL. Phase II study of irinotecan and temozolomide in children with relapsed or refractory neuroblastoma: a Children's Oncology Group study. J Clin Oncol. 2011 Jan 10;29(2):208-13. doi: 10.1200/JCO.2010.31.7107. Epub 2010 Nov 29.