Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Cisplatin-Based Chemotherapy and/or Surgery in Treating Young Patients With Adrenocortical Tumor

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Active	Under 22 at diagnosis	NCI	COG-ARAR0332 ARAR0332, NCT00304070

Objectives

Primary

1. Describe the outcome of patients with stage I adrenocortical tumor (ACT) treated with surgery alone.
2. Describe the outcome of patients with stage II ACT treated with radical adrenalectomy plus regional retroperitoneal lymph node dissection.
3. Describe the outcome of patients with unresectable or metastatic ACT treated with mitotane and a cisplatin-based chemotherapy regimen.

Secondary

1. Determine the feasibility and complications associated with the use of radical adrenalectomy and regional node dissection in these patients.
2. Determine the toxicity of mitotane when administered with cisplatin, etoposide, and doxorubicin hydrochloride in patients with residual disease after surgery, inoperable tumors, or metastatic disease at diagnosis.
3. Determine, prospectively, the frequency of tumor spillage during surgery in these patients.
4. Determine the frequency of lymph node involvement in these patients.
5. Compare the incidence and type of germline p53 mutation in non-Brazilian children and children from Southern Brazil.
6. Characterize the cooperating molecular alterations associated with ACT.
7. Determine the presence of embryonal markers in children with ACT.

Entry Criteria

Disease Characteristics:

• Histologically confirmed adrenocortical carcinoma
  • Newly diagnosed disease within the past 3 weeks
  • Any disease stage allowed

Prior/Concurrent Therapy:

• No previous chemotherapy for adrenocortical carcinoma

Patient Characteristics:

• Lansky performance status 60-100% (for patients ≤ 16 years old)
• Karnofsky performance status 60-100% (for patients > 16 years old)
• Absolute neutrophil count ≥ 750/mm³
• Platelet count ≥ 75,000/mm³
• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR serum creatinine based on age as follows:
  • ≤ 0.8 mg/dL (for patients ≤ 5 years old)
  • ≤ 1.0 mg/dL (for patients 6 to 10 years old)
  • ≤ 1.2 mg/dL (for patients 11 to 15 years old)
  • ≤ 1.5 mg/dL (for patients > 15 years old)
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST or ALT < 2.5 times ULN
• Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide angiogram
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

Expected Enrollment

A total of 235 patients will be accrued for this study.

Outcomes

Primary tumor measurement
Measurable metastatic disease
Response of metastatic target lesions
Nonmeasurable metastatic disease
Overall response

Outline

This is a multicenter study. Patients are stratified according to disease stage ( I vs II vs III or IV).

• Stratum I (stage I disease): Patients undergo primary tumor resection and retroperitoneal lymph node sampling followed by observation. Patients who have undergone prior surgery without nodal sampling undergo observation only.



• Stratum II (stage II disease): Patients undergo primary tumor resection and extended regional lymph node dissection followed by observation. Patients who have undergone prior surgery with simple resection of the primary tumor undergo exploratory surgery with extended regional lymph node dissection followed by observation.



• Stratum III (stage III or IV disease):
  • Induction chemotherapy: Patients receive cisplatin-based chemotherapy comprising oral mitotane once daily on days 1-21; cisplatin IV over 6 hours on days 1-2; etoposide IV over 1 hour on days 1-3; and doxorubicin hydrochloride IV over 1 hour on days 4-5. Patients also receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 6 and continuing until blood counts recover OR pegfilgrastim SC once on day 6. Treatment repeats every 21 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease or partial response proceed to surgery. Patients with a complete response proceed directly to continuation chemotherapy.
  
  
  
  • Surgery: Patients with stage III disease undergo extended surgery and regional lymph node dissection. Patients with stage IV disease undergo primary tumor resection (if feasible) with regional lymph node dissection and resection of the metastases. Patients then proceed to continuation chemotherapy.
  
  
  
  • Continuation chemotherapy: Patients receive additional cisplatin-based chemotherapy (as in induction chemotherapy) for 4-6 courses followed by mitotane alone for an additional 2 months. Patients with stage IV disease then proceed to additional surgery when feasible.
  
  
  
  • Additional Surgery: Patients with stage IV disease may undergo additional primary tumor resection with regional lymph node dissection and resection (or re-resection) of the metastases.
  
  
  

After completion of study treatment, patients are followed periodically for at least 5 years.

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Carlos Rodriguez-Galindo, MD, Protocol chair		Ph: 901-595-2203 Email: Carlos.Rodriguez-Galindo@stjude.org
Raul Ribeiro, MD, Protocol co-chair		Ph: 901-495-3694 Email: raul.ribeiro@stjude.org

U.S.A.
Alabama
	Birmingham
	Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
		Clinical Trials Office - Lurleen Wallace Comprehensive Cancer	Ph:  205-934-0309
Arkansas
	Little Rock
	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
		Clinical Trial Office - Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Ph:  501-686-8274
California
	Downey
	Southern California Permanente Medical Group
		Robert Cooper	Ph:  323-783-5307
	Long Beach
	Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
		Jerry Finklestein	Ph:  562-492-1062
	Madera
	Children's Hospital Central California
		Vonda Crouse	Ph:  559-353-5480
Colorado
	Aurora
	Children's Hospital Center for Cancer and Blood Disorders
		Kelly Maloney	Ph:  720-777-6673
Connecticut
	Farmington
	Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
		Clinical Trials Office - Carole and Ray Neag Comprehensive Cancer Center	Ph:  800-579-7822
Delaware
	Wilmington
	Alfred I. duPont Hospital for Children
		Clinical Trials Office - Alfred I. duPont Hospital for Children	Ph:  302-651-5755
District of Columbia
	Washington
	Children's National Medical Center
		Clinical Trials Office - Children's National Medical Center	Ph:  202-884-2549
Florida
	Fort Myers
	Lee Cancer Care of Lee Memorial Health System
		Clinical Trials Office - Lee Cancer Care of Lee Memorial Health System	Ph:  877-680-0008
	Jacksonville
	Nemours Children's Clinic
		Eric Sandler	Ph:  904-697-3793
	Pensacola
	Sacred Heart Cancer Center at Sacred Heart Hospital
		Clinical Trials Office - Sacred Heart Cancer Center	Ph:  850-416-4611
	St. Petersburg
	All Children's Hospital
		Gregory Hale	Ph:  727-767-4176
	Tampa
	St. Joseph's Cancer Institute at St. Joseph's Hospital
		Clinical Trials Office - St. Joseph's Cancer Institute	Ph:  800-882-4123
	West Palm Beach
	Kaplan Cancer Center at St. Mary's Medical Center
		Narayana Gowda	Ph:  561-844-6363
Hawaii
	Tripler AMC
	Tripler Army Medical Center
		Melissa Forouhar	Ph:  253-986-6144
Illinois
	Chicago
	Children's Memorial Hospital - Chicago
		Stewart Goldman	Ph:  773-880-4598x3270
	University of Chicago Cancer Research Center
		Clinical Trials Office - University of Chicago Cancer Research Center	Ph:  773-834-7424
	Peoria
	Saint Jude Midwest Affiliate
		Stephen Smith	Ph:  309-624-4945
	Springfield
	Simmons Cooper Cancer Institute
		Clinical Trials Office - Simmons Cooper Cancer Institute	Ph:  217-545-7929
Indiana
	Indianapolis
	Indiana University Melvin and Bren Simon Cancer Center
		Clinical Trials Office - Indiana University Cancer Center	Ph:  317-274-2552
Kentucky
	Lexington
	Lucille P. Markey Cancer Center at University of Kentucky
		Clinical Trials Office - Markey Cancer Center at University of Kentucky Chandler Medical Center	Ph:  859-257-3379
	Louisville
	Kosair Children's Hospital
		Clinical Trials Office - Kosair Children's Hospital	Ph:  502-629-5500
			Email: CancerResource@nortonhealthcare.org
Louisiana
	Alexandria
	Tulane Cancer Center Office of Clinical Research
		Clinical Trials Office - Tulane Cancer Center	Ph:  504-988-6121
Maryland
	Baltimore
	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
		Joseph Wiley	Ph:  410-601-5864
Massachusetts
	Boston
	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
		Suzanne Shusterman	Ph:  617-632-4901
Michigan
	Detroit
	Barbara Ann Karmanos Cancer Institute
		Clinical Trials Office - Barbara Ann Karmanos Cancer Institute	Ph:  313-576-9363
	Lansing
	Breslin Cancer Center at Ingham Regional Medical Center
		Clinical Trials Office - Breslin Cancer Center at Ingham Regional Medical Center	Ph:  517-334-2765
Missouri
	Kansas City
	Children's Mercy Hospital
		Maxine Hetherington	Ph:  816-234-3265
New Jersey
	Hackensack
	Hackensack University Medical Center Cancer Center
		Clinical Trials Office - Hackensack University Medical Center Cancer Center	Ph:  201-996-2879
	Morristown
	Overlook Hospital
		Hazem Mahmoud	Ph:  973-971-6720
New York
	Albany
	Albany Medical Center Hospital
		Vikramjit Kanwar	Ph:  518-262-5513x25265
North Carolina
	Chapel Hill
	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
		Clinical Trials Office - Lineberger Comprehensive Cancer Center	Ph:  877-668-0683; 919-966-4432
Ohio
	Akron
	Akron Children's Hospital
		Clinical Trials Office - Akron Children's Hospital	Ph:  330-543-3193
	Cincinnati
	Cincinnati Children's Hospital Medical Center
		Clinical Trials Office - Cincinnati Children's Hospital Medical Center	Ph:  513-636-0161
	Cleveland
	Cleveland Clinic Taussig Cancer Center
		Clinical Trials Office - Cleveland Clinic Taussig Cancer Center	Ph:  866-223-8100
	Rainbow Babies and Children's Hospital
		John Letterio	Ph:  216-844-3345
	Columbus
	Nationwide Children's Hospital
		Amanda Termuhlen	Ph:  614-722-3552
	Dayton
	Children's Medical Center - Dayton
		Emmett Broxson	Ph:  937-641-3111
Oklahoma
	Oklahoma City
	Oklahoma University Cancer Institute
		Rene McNall-Knapp	Ph:  405-271-5311
Pennsylvania
	Danville
	Geisinger Cancer Institute at Geisinger Health
		Clinical Trials Office - Geisinger Cancer Institute	Ph:  570-271-5251
	Philadelphia
	Children's Hospital of Philadelphia
		Richard Aplenc	Ph:  267-426-7252
	Pittsburgh
	Children's Hospital of Pittsburgh
		Clinical Trials Office - Children's Hospital of Pittsburgh	Ph:  412-692-5573
South Carolina
	Columbia
	Palmetto Health South Carolina Cancer Center
		Clinical Trials Office - Palmetto Health South Carolina Cancer Center	Ph:  803-434-3680
Tennessee
	Memphis
	St. Jude Children's Research Hospital
		Clinical Trials Office - St. Jude Children's Research Hospital	Ph:  901-595-4644
Texas
	Corpus Christi
	Driscoll Children's Hospital
		Clinical Trials Office - Driscoll Children's Hospital	Ph:  361-694-5311
	Houston
	Baylor University Medical Center - Houston
		Patrick Thompson	Ph:  832-824-4029
	San Antonio
	Methodist Children's Hospital of South Texas
		Michael Grimley	Ph:  210-575-7268
Utah
	Salt Lake City
	Primary Children's Medical Center
		Phillip Barnette	Ph:  801-662-4700
Virginia
	Norfolk
	Children's Hospital of The King's Daughters
		Eric Lowe	Ph:  757-668-7243
Washington
	Seattle
	Children's Hospital and Regional Medical Center - Seattle
		Julie Park	Ph:  206-987-1947
West Virginia
	Charleston
	West Virginia University Health Sciences Center - Charleston
		Allen Chauvenet	Ph:  304-388-1552
Wisconsin
	Milwaukee
	Midwest Children's Cancer Center at Children's Hospital of Wisconsin
		Bruce Camitta	Ph:  414-456-4106
Canada
	Quebec
	Centre Hospitalier Universitaire de Quebec
		Bruno Michon	Ph:  418-656-4141
Alberta
	Calgary
	Alberta Children's Hospital
		Douglas Strother	Ph:  403-955-7272
British Columbia
	Vancouver
	Children's & Women's Hospital of British Columbia
		Mason Bond	Ph:  604-875-2322
Nova Scotia
	Halifax
	IWK Health Centre
		Margaret Yhap	Ph:  902-470-8778
Ontario
	Hamilton
	McMaster Children's Hospital at Hamilton Health Sciences
		Carol Portwine	Ph:  905-521-2100x73464
	Toronto
	Hospital for Sick Children
		Sylvain Baruchel	Ph:  416-813-7795
Quebec
	Montreal
	Hopital Sainte Justine
		Yvan Samson	Ph:  418-656-4141x47191
		Yvan Samson	Ph:  514-345-4969
	Montreal Children's Hospital at McGill University Health Center
		Sharon Abish	Ph:  514-412-4400x22219

Registry Information
Official Title		Treatment of Adrenocortical Tumors With Surgery Plus Lymph Node Dissection and Multiagent Chemotherapy
Trial Start Date		2006-09-18
Trial Completion Date		2011-07-16 (estimated)
Registered in ClinicalTrials.gov		NCT00304070
Date Submitted to PDQ		2006-01-19
Information Last Verified		2009-05-13
NCI Grant/Contract Number		CA98543