Irinotecan and Temozolomide in Treating Young Patients With Recurrent Neuroblastoma

NCT ID: NCT00311584

Last Updated: 2014-09-30

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

59 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-04-30

Study Completion Date

2013-12-31

Brief Summary

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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

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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.

Conditions

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Neuroblastoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Disease measurable by CT or MRI scan (Irinotecan/Temozolomide)

Measurable by CT scan (Computed Tomography) or MRI scan (Magnetic Resonance Imaging). Patients receive irinotecan hydrochloride IV (10 mg/m2/dose) over 1 hour on days 1-5 and 8-12 and oral temozolomide (100 mg/m2/dose) on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

irinotecan hydrochloride

Intervention Type DRUG

Given IV

temozolomide

Intervention Type DRUG

Given IV

Disease eval by bone marrow or MIBG (Irinotecan/Temozolomide)

Evaluation by bone marrow or MIBG scan (metaiodobenzylguanidine scan, a radiopharmaceutical). Patients receive irinotecan hydrochloride IV (10 mg/m2/dose) over 1 hour on days 1-5 and 8-12 and oral temozolomide (100 mg/m2/dose) on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

irinotecan hydrochloride

Intervention Type DRUG

Given IV

temozolomide

Intervention Type DRUG

Given IV

Interventions

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irinotecan hydrochloride

Given IV

Intervention Type DRUG

temozolomide

Given IV

Intervention Type DRUG

Other Intervention Names

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CPT-11 NSC #616348 TEMODAR NSC #362856

Eligibility Criteria

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Inclusion Criteria

* 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
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Rochelle Bagatell, MD

Role: STUDY_CHAIR

University of Arizona

Cynthia S. Kretschmar, MD

Role: STUDY_CHAIR

Floating Hospital for Children at Tufts - New England Medical Center

Locations

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Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham

Birmingham, Alabama, United States

Site Status

Arizona Cancer Center at University of Arizona Health Sciences Center

Tucson, Arizona, United States

Site Status

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Southern California Permanente Medical Group

Downey, California, United States

Site Status

Loma Linda University Cancer Institute at Loma Linda University Medical Center

Loma Linda, California, United States

Site Status

Jonathan Jaques Children's Cancer Center at Miller Children's Hospital

Long Beach, California, United States

Site Status

Childrens Hospital Los Angeles

Los Angeles, California, United States

Site Status

Children's Hospital Central California

Madera, California, United States

Site Status

Children's Hospital and Research Center Oakland

Oakland, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

Sutter Cancer Center

Sacramento, California, United States

Site Status

Kaiser Permanente Medical Center - Oakland

Sacramento, California, United States

Site Status

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Site Status

Stanford Cancer Center

Stanford, California, United States

Site Status

Children's Hospital Center for Cancer and Blood Disorders

Aurora, Colorado, United States

Site Status

Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center

Farmington, Connecticut, United States

Site Status

Alfred I. duPont Hospital for Children

Wilmington, Delaware, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

Lee Cancer Care of Lee Memorial Health System

Fort Myers, Florida, United States

Site Status

University of Florida Shands Cancer Center

Gainesville, Florida, United States

Site Status

Nemours Children's Clinic

Jacksonville, Florida, United States

Site Status

University of Miami Sylvester Comprehensive Cancer Center - Miami

Miami, Florida, United States

Site Status

Miami Children's Hospital

Miami, Florida, United States

Site Status

Florida Hospital Cancer Institute at Florida Hospital Orlando

Orlando, Florida, United States

Site Status

Sacred Heart Cancer Center at Sacred Heart Hospital

Pensacola, Florida, United States

Site Status

All Children's Hospital

St. Petersburg, Florida, United States

Site Status

St. Joseph's Cancer Institute at St. Joseph's Hospital

Tampa, Florida, United States

Site Status

Kaplan Cancer Center at St. Mary's Medical Center

West Palm Beach, Florida, United States

Site Status

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Site Status

Cancer Research Center of Hawaii

Honolulu, Hawaii, United States

Site Status

Mountain States Tumor Institute at St. Luke's Regional Medical Center

Boise, Idaho, United States

Site Status

University of Illinois Cancer Center

Chicago, Illinois, United States

Site Status

Children's Memorial Hospital - Chicago

Chicago, Illinois, United States

Site Status

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Site Status

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

Blank Children's Hospital

Des Moines, Iowa, United States

Site Status

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, United States

Site Status

Lucille P. Markey Cancer Center at University of Kentucky

Lexington, Kentucky, United States

Site Status

Kosair Children's Hospital

Louisville, Kentucky, United States

Site Status

Children's Hospital of New Orleans

New Orleans, Louisiana, United States

Site Status

Alvin and Lois Lapidus Cancer Institute at Sinai Hospital

Baltimore, Maryland, United States

Site Status

Floating Hospital for Children at Tufts - New England Medical Center

Boston, Massachusetts, United States

Site Status

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

C.S. Mott Children's Hospital at University of Michigan Medical Center

Ann Arbor, Michigan, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Hurley Medical Center

Flint, Michigan, United States

Site Status

Butterworth Hospital at Spectrum Health

Grand Rapids, Michigan, United States

Site Status

Van Elslander Cancer Center at St. John Hospital and Medical Center

Grosse Pointe Woods, Michigan, United States

Site Status

CCOP - Kalamazoo

Kalamazoo, Michigan, United States

Site Status

Breslin Cancer Center at Ingham Regional Medical Center

Lansing, Michigan, United States

Site Status

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States

Site Status

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

University of Mississippi Cancer Clinic

Jackson, Mississippi, United States

Site Status

Children's Mercy Hospital

Kansas City, Missouri, United States

Site Status

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, United States

Site Status

Children's Hospital

Omaha, Nebraska, United States

Site Status

Sunrise Hospital and Medical Center

Las Vegas, Nevada, United States

Site Status

Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, United States

Site Status

Overlook Hospital

Morristown, New Jersey, United States

Site Status

Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

New Brunswick, New Jersey, United States

Site Status

Newark Beth Israel Medical Center

Newark, New Jersey, United States

Site Status

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Site Status

Maimonides Cancer Center at Maimonides Medical Center

Brooklyn, New York, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

New York, New York, United States

Site Status

James P. Wilmot Cancer Center at University of Rochester Medical Center

Rochester, New York, United States

Site Status

Stony Brook University Cancer Center

Stony Brook, New York, United States

Site Status

SUNY Upstate Medical University Hospital

Syracuse, New York, United States

Site Status

Albert Einstein Cancer Center at Albert Einstein College of Medicine

The Bronx, New York, United States

Site Status

New York Medical College

Valhalla, New York, United States

Site Status

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, United States

Site Status

Presbyterian Cancer Center at Presbyterian Hospital

Charlotte, North Carolina, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

Akron Children's Hospital

Akron, Ohio, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Children's Medical Center - Dayton

Dayton, Ohio, United States

Site Status

Lehigh Valley Hospital - Muhlenberg

Bethlehem, Pennsylvania, United States

Site Status

Geisinger Cancer Institute at Geisinger Health

Danville, Pennsylvania, United States

Site Status

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Palmetto Health South Carolina Cancer Center

Columbia, South Carolina, United States

Site Status

East Tennessee Children's Hospital

Knoxville, Tennessee, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Dell Children's Medical Center of Central Texas

Austin, Texas, United States

Site Status

Driscoll Children's Hospital

Corpus Christi, Texas, United States

Site Status

Medical City Dallas Hospital

Dallas, Texas, United States

Site Status

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, United States

Site Status

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, United States

Site Status

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, United States

Site Status

Covenant Children's Hospital

Lubbock, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Methodist Children's Hospital of South Texas

San Antonio, Texas, United States

Site Status

CCOP - Scott and White Hospital

Temple, Texas, United States

Site Status

Primary Children's Medical Center

Salt Lake City, Utah, United States

Site Status

Fletcher Allen Health Care - University Health Center Campus

Burlington, Vermont, United States

Site Status

Children's Hospital of The King's Daughters

Norfolk, Virginia, United States

Site Status

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, United States

Site Status

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States

Site Status

Providence Cancer Center at Sacred Heart Medical Center

Spokane, Washington, United States

Site Status

West Virginia University Health Sciences Center - Charleston

Charleston, West Virginia, United States

Site Status

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, United States

Site Status

Midwest Children's Cancer Center

Milwaukee, Wisconsin, United States

Site Status

John Hunter Hospital

Newcastle, New South Wales, Australia

Site Status

Westmead Institute for Cancer Research at Westmead Hospital

Westmead, New South Wales, Australia

Site Status

Royal Children's Hospital

Brisbane, Queensland, Australia

Site Status

Royal Children's Hospital

Parkville, Victoria, Australia

Site Status

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Site Status

University of Alberta Hospital

Edmonton, Alberta, Canada

Site Status

Children's & Women's Hospital of British Columbia

Vancouver, British Columbia, Canada

Site Status

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Site Status

IWK Health Centre

Halifax, Nova Scotia, Canada

Site Status

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, Canada

Site Status

Children's Hospital of Western Ontario

London, Ontario, Canada

Site Status

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Montreal Children's Hospital at McGill University Health Center

Montreal, Quebec, Canada

Site Status

Hopital Sainte Justine

Montreal, Quebec, Canada

Site Status

Allan Blair Cancer Centre at Pasqua Hospital

Regina, Saskatchewan, Canada

Site Status

Saskatoon Cancer Centre at the University of Saskatchewan

Saskatoon, Saskatchewan, Canada

Site Status

Centre Hospitalier Universitaire de Quebec

Québec, , Canada

Site Status

Countries

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United States Australia Canada

References

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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.

Reference Type RESULT
PMID: 21115869 (View on PubMed)

Other Identifiers

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CDR0000465487

Identifier Type: OTHER

Identifier Source: secondary_id

COG-ANBL0421

Identifier Type: OTHER

Identifier Source: secondary_id

ANBL0421

Identifier Type: -

Identifier Source: org_study_id

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