Irinotecan and Temozolomide in Treating Young Patients With Recurrent Neuroblastoma

NCT00311584 | Completed Phase 2 Results DMC

• 3 other identifiers: ANBL0421CDR0000465487COG-ANBL0421
• Study Type: interventional
• Target: 59
• Locations: 3 countries
• Sites: 128

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.

Conditions

Neuroblastoma

Keywords

recurrent neuroblastoma

Outcome Measures

Primary Outcomes (1)

• Overall Response - Complete Response (CR), Very Good Partial Response (VGPR) and Partial Response (PR)

  The patient's best overall response obtained during Reporting Periods 1 and 2 will be scored as "best response". Patients enrolled on Stratum 1 with bone marrow disease, a responder has no tumor cells detectable by routine morphology on 2 subsequent bilateral bone marrow aspirates and biopsies done at least 3 weeks apart. For patients enrolled on stratum 1 with MIBG only disease, response will be assessed using the Curie scale. Patients who have complete resolution of all MIBG positive lesions (CR) or resolution of at least one MIBG positive lesion with persistence of other lesions (PR) will be considered responders. For Stratum 2 a responder is defined to be a patient who achieves a best overall response of CR, VGPR or PR from CT/MRI scans from central review using (RECIST) Response Evaluation Criteria in Solid Tumor. A responder is defined to be a patient who achieves a best overall response of CR (Complete Response), VGPR (Very Good Partial Response) or PR (Partial Response).

  up to 6 courses of therapy, or about 6 months

Study Arms (2)

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

EXPERIMENTAL

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.

Drug: irinotecan hydrochloride; Drug: temozolomide

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

EXPERIMENTAL

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.

Drug: irinotecan hydrochloride; Drug: temozolomide

Interventions

irinotecan hydrochloride DRUG

Given IV

Also known as: CPT-11, NSC #616348

Disease eval by bone marrow or MIBG (Irinotecan/Temozolomide); Disease measurable by CT or MRI scan (Irinotecan/Temozolomide)

temozolomide DRUG

Given IV

Also known as: TEMODAR, NSC #362856

Disease eval by bone marrow or MIBG (Irinotecan/Temozolomide); Disease measurable by CT or MRI scan (Irinotecan/Temozolomide)

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (128)

Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham

Birmingham, Alabama, 35294, United States

Location

Arizona Cancer Center at University of Arizona Health Sciences Center

Tucson, Arizona, 85724-5024, United States

Location

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Southern California Permanente Medical Group

Downey, California, 90242-2814, United States

Location

Loma Linda University Cancer Institute at Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

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

Long Beach, California, 90801, United States

Location

Childrens Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital Central California

Madera, California, 93638-8762, United States

Location

Children's Hospital and Research Center Oakland

Oakland, California, 94609, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Sutter Cancer Center

Sacramento, California, 95816, United States

Location

Kaiser Permanente Medical Center - Oakland

Sacramento, California, 95825, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Stanford Cancer Center

Stanford, California, 94305-5824, United States

Location

Children's Hospital Center for Cancer and Blood Disorders

Aurora, Colorado, 80045, United States

Location

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

Farmington, Connecticut, 06360-2875, United States

Location

Alfred I. duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

Location

Lee Cancer Care of Lee Memorial Health System

Fort Myers, Florida, 33901, United States

Location

University of Florida Shands Cancer Center

Gainesville, Florida, 32610-0232, United States

Location

Nemours Children's Clinic

Jacksonville, Florida, 32207, United States

Location

University of Miami Sylvester Comprehensive Cancer Center - Miami

Miami, Florida, 33136, United States

Location

Miami Children's Hospital

Miami, Florida, 33155, United States

Location

Florida Hospital Cancer Institute at Florida Hospital Orlando

Orlando, Florida, 32803-1273, United States

Location

Sacred Heart Cancer Center at Sacred Heart Hospital

Pensacola, Florida, 32504, United States

Location

All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

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

Tampa, Florida, 33607, United States

Location

Kaplan Cancer Center at St. Mary's Medical Center

West Palm Beach, Florida, 33407, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Cancer Research Center of Hawaii

Honolulu, Hawaii, 96813, United States

Location

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

Boise, Idaho, 83712-6297, United States

Location

University of Illinois Cancer Center

Chicago, Illinois, 60612-7243, United States

Location

Children's Memorial Hospital - Chicago

Chicago, Illinois, 60614, United States

Location

University of Chicago Cancer Research Center

Chicago, Illinois, 60637-1470, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202-5289, United States

Location

Blank Children's Hospital

Des Moines, Iowa, 50309, United States

Location

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, 52242-1002, United States

Location

Lucille P. Markey Cancer Center at University of Kentucky

Lexington, Kentucky, 40536-0093, United States

Location

Kosair Children's Hospital

Louisville, Kentucky, 40232, United States

Location

Children's Hospital of New Orleans

New Orleans, Louisiana, 70118, United States

Location

Alvin and Lois Lapidus Cancer Institute at Sinai Hospital

Baltimore, Maryland, 21215, United States

Location

Floating Hospital for Children at Tufts - New England Medical Center

Boston, Massachusetts, 02111, United States

Location

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

Boston, Massachusetts, 02115, United States

Location

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

Ann Arbor, Michigan, 48109-0286, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-1379, United States

Location

Hurley Medical Center

Flint, Michigan, 48503, United States

Location

Butterworth Hospital at Spectrum Health

Grand Rapids, Michigan, 49503-2560, United States

Location

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

Grosse Pointe Woods, Michigan, 48236, United States

Location

CCOP - Kalamazoo

Kalamazoo, Michigan, 49007-5341, United States

Location

Breslin Cancer Center at Ingham Regional Medical Center

Lansing, Michigan, 48910, United States

Location

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, 55404, United States

Location

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

University of Mississippi Cancer Clinic

Jackson, Mississippi, 39216-4505, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, 63110, United States

Location

Children's Hospital

Omaha, Nebraska, 68114-4113, United States

Location

Sunrise Hospital and Medical Center

Las Vegas, Nevada, 89109-2306, United States

Location

Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, 07601, United States

Location

Overlook Hospital

Morristown, New Jersey, 07962, United States

Location

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

New Brunswick, New Jersey, 08903, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87131-5636, United States

Location

Maimonides Cancer Center at Maimonides Medical Center

Brooklyn, New York, 11219, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

New York, New York, 10032, United States

Location

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

Rochester, New York, 14642, United States

Location

Stony Brook University Cancer Center

Stony Brook, New York, 11794-9446, United States

Location

SUNY Upstate Medical University Hospital

Syracuse, New York, 13210, United States

Location

Albert Einstein Cancer Center at Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

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

Chapel Hill, North Carolina, 27599-7295, United States

Location

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, 28232-2861, United States

Location

Presbyterian Cancer Center at Presbyterian Hospital

Charlotte, North Carolina, 28233-3549, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308-1062, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106-5000, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205-2696, United States

Location

Children's Medical Center - Dayton

Dayton, Ohio, 45404-1815, United States

Location

Lehigh Valley Hospital - Muhlenberg

Bethlehem, Pennsylvania, 18107, United States

Location

Geisinger Cancer Institute at Geisinger Health

Danville, Pennsylvania, 17822-0001, United States

Location

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-9786, United States

Location

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134-1095, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Palmetto Health South Carolina Cancer Center

Columbia, South Carolina, 29203, United States

Location

East Tennessee Children's Hospital

Knoxville, Tennessee, 37901, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

Dell Children's Medical Center of Central Texas

Austin, Texas, 78723, United States

Location

Driscoll Children's Hospital

Corpus Christi, Texas, 78411, United States

Location

Medical City Dallas Hospital

Dallas, Texas, 75230, United States

Location

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

Dallas, Texas, 75390, United States

Location

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, 76104, United States

Location

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

Location

Covenant Children's Hospital

Lubbock, Texas, 79410, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78207, United States

Location

Methodist Children's Hospital of South Texas

San Antonio, Texas, 78229-3993, United States

Location

CCOP - Scott and White Hospital

Temple, Texas, 76508, United States

Location

Primary Children's Medical Center

Salt Lake City, Utah, 84113-1100, United States

Location

Fletcher Allen Health Care - University Health Center Campus

Burlington, Vermont, 05401, United States

Location

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507-1971, United States

Location

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, 23298-0037, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

Providence Cancer Center at Sacred Heart Medical Center

Spokane, Washington, 99220-2555, United States

Location

West Virginia University Health Sciences Center - Charleston

Charleston, West Virginia, 25302, United States

Location

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, 54307-3508, United States

Location

Midwest Children's Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

John Hunter Hospital

Newcastle, New South Wales, 2310, Australia

Location

Westmead Institute for Cancer Research at Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Royal Children's Hospital

Brisbane, Queensland, 4029, Australia

Location

Royal Children's Hospital

Parkville, Victoria, 3052, Australia

Location

Princess Margaret Hospital for Children

Perth, Western Australia, 6001, Australia

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 1Z2, Canada

Location

Children's & Women's Hospital of British Columbia

Vancouver, British Columbia, V6H 3V4, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

IWK Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada

Location

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, L8N 3Z5, Canada

Location

Children's Hospital of Western Ontario

London, Ontario, N6A 4G5, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Montreal Children's Hospital at McGill University Health Center

Montreal, Quebec, H3H 1P3, Canada

Location

Hopital Sainte Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Allan Blair Cancer Centre at Pasqua Hospital

Regina, Saskatchewan, S4T 7T1, Canada

Location

Saskatoon Cancer Centre at the University of Saskatchewan

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Centre Hospitalier Universitaire de Quebec

Québec, G1V 4G2, Canada

Location

Related Publications (1)

• 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.

  PMID: 21115869 RESULT

MeSH Terms

Conditions

Neuroblastoma

Interventions

Irinotecan; Temozolomide

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Results Reporting Coordinator
• Organization: Children's Oncology Group

resultsreportingcoordinator@childrensoncologygroup.org

626-447-0064

Study Officials

• Rochelle Bagatell, MD

  University of Arizona

  STUDY CHAIR

• Cynthia S. Kretschmar, MD

  Floating Hospital for Children at Tufts - New England Medical Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2006
• First Posted: April 6, 2006
• Study Start: April 1, 2006
• Primary Completion: March 1, 2009
• Study Completion: December 1, 2013
• Last Updated: September 30, 2014
• Results First Posted: January 16, 2014

Record last verified: 2014-09

Locations

CA (13); US (110); AU (5)