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Stage I Adrenal Cortical Carcinoma AJCC v7Phase 3NCT00304070

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

A Phase 3 study testing Cisplatin, Conventional Surgery and Doxorubicin Hydrochloride in people with Stage I Adrenal Cortical Carcinoma AJCC v7 and Stage II Adrenal Cortical Carcinoma AJCC v7, run by Children's Oncology Group at 91 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase III clinical trial is studying how well cisplatin-based chemotherapy and/or surgery works in treating young patients with stage I, stage II, stage III or stage IV adrenocortical cancer. Read more about this study

Who is it for?
Ages Up to 21 years
What is being tested?
Cisplatin, Conventional Surgery and Doxorubicin Hydrochloride
Could I receive a placebo?
No, everyone receives an active treatment
How many people
78 participants
Where
91 sitesin 4 countries
Study dates
3 May 2007to 30 Jun 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Histologically confirmed adrenocortical carcinoma
  • Newly diagnosed disease within the past 3 weeks
  • Any disease stage allowed
  • Lansky performance status 60-100% (for patients ≤ 16 years old)
  • Karnofsky performance status 60-100% (for patients > 16 years old)
  • Absolute neutrophil count ≥ 750/mm^3
Show all 23Show fewer
  • Platelet count ≥ 75,000/mm^3
  • Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR serum creatinine based on age as follows:
  • 0.4 mg/dL (1 month to < 6 months)
  • 0.5 mg/dL (6 months to < 1 year of age)
  • 0.6 mg/dL (1 to < 2 years of age
  • 0.8 mg/dL (2 to < 6 years of age)
  • 1.0 mg/dL (6 to < 10 years of age)
  • 1.2 mg/dL (10 to < 13 years of age)
  • 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
  • 1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)
  • 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
  • No previous chemotherapy for adrenocortical carcinoma

Who cannot join

None listed.

Trial locations and contacts

91 sites in 4 countries.

91 sites in 4 countries

United States81 sites

  • Children's Hospital Medical Center of Akron

    Akron, Ohio, 44308

  • Albany Medical Center

    Albany, New York, 12208

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Sinai Hospital of Baltimore

    Baltimore, Maryland, 21215

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889-5600

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • University of Vermont and State Agricultural College

    Burlington, Vermont, 05405

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • West Virginia University Charleston Division

    Charleston, West Virginia, 25304

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60611

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Rainbow Babies and Childrens Hospital

    Cleveland, Ohio, 44106

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Prisma Health Richland Hospital

    Columbia, South Carolina, 29203

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • Driscoll Children's Hospital

    Corpus Christi, Texas, 78411

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • Dayton Children's Hospital

    Dayton, Ohio, 45404

  • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

    Denver, Colorado, 80218

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Kaiser Permanente Downey Medical Center

    Downey, California, 90242

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Michigan State University Clinical Center

    East Lansing, Michigan, 48824-7016

  • University of Connecticut

    Farmington, Connecticut, 06030

  • Lee Memorial Health System

    Fort Myers, Florida, 33901

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

  • BI-LO Charities Children's Cancer Center

    Greenville, South Carolina, 29605

  • Greenville Cancer Treatment Center

    Greenville, South Carolina, 29605

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Connecticut Children's Medical Center

    Hartford, Connecticut, 06106

  • Tripler Army Medical Center

    Honolulu, Hawaii, 96859

  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

    Houston, Texas, 77030

  • Indiana University/Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • Nemours Children's Clinic-Jacksonville

    Jacksonville, Florida, 32207

  • Children's Mercy Hospitals and Clinics

    Kansas City, Missouri, 64108

  • Alliance for Childhood Diseases/Cure 4 the Kids Foundation

    Las Vegas, Nevada, 89135

  • Nevada Cancer Research Foundation NCORP

    Las Vegas, Nevada, 89169

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • Miller Children's and Women's Hospital Long Beach

    Long Beach, California, 90806

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Norton Children's Hospital

    Louisville, Kentucky, 40202

  • Valley Children's Hospital

    Madera, California, 93636

  • Saint Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53226

  • University of Minnesota/Masonic Cancer Center

    Minneapolis, Minnesota, 55455

  • Morristown Medical Center

    Morristown, New Jersey, 07960

  • Tulane University Health Sciences Center

    New Orleans, Louisiana, 70112

  • Newark Beth Israel Medical Center

    Newark, New Jersey, 07112

  • Children's Hospital of The King's Daughters

    Norfolk, Virginia, 23507

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Children's Hospital of Orange County

    Orange, California, 92868

  • Nemours Children's Clinic - Orlando

    Orlando, Florida, 32806

  • Lucile Packard Children's Hospital Stanford University

    Palo Alto, California, 94304

  • Nemours Children's Clinic - Pensacola

    Pensacola, Florida, 32504

  • Sacred Heart Hospital

    Pensacola, Florida, 32504

  • Saint Jude Midwest Affiliate

    Peoria, Illinois, 61637

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • University of Rochester

    Rochester, New York, 14642

  • Primary Children's Hospital

    Salt Lake City, Utah, 84113

  • Methodist Children's Hospital of South Texas

    San Antonio, Texas, 78229

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Southern Illinois University School of Medicine

    Springfield, Illinois, 62702

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Johns Hopkins All Children's Hospital

    St. Petersburg, Florida, 33701

  • Overlook Hospital

    Summit, New Jersey, 07902

  • Saint Joseph's Hospital/Children's Hospital-Tampa

    Tampa, Florida, 33607

  • Banner University Medical Center - Tucson

    Tucson, Arizona, 85719

  • New York Medical College

    Valhalla, New York, 10595

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

  • Saint Mary's Hospital

    West Palm Beach, Florida, 33407

  • Alfred I duPont Hospital for Children

    Wilmington, Delaware, 19803

Other trials in United States

Canada7 sites

  • Alberta Children's Hospital

    Calgary, Alberta, T3B 6A8

  • IWK Health Centre

    Halifax, Nova Scotia, B3K 6R8

  • McMaster Children's Hospital at Hamilton Health Sciences

    Hamilton, Ontario, L8N 3Z5

  • Centre Hospitalier Universitaire Sainte-Justine

    Montreal, Quebec, H3T 1C5

  • Centre Hospitalier Universitaire de Quebec

    Québec, G1V 4G2

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

  • British Columbia Children's Hospital

    Vancouver, British Columbia, V6H 3V4

Other trials in Canada

Brazil2 sites

  • Boldrini Children's Cancer Center

    Campinas, São Paulo, 13083210

  • Instituto De Oncologia Pediatrica

    São Paulo, 04023-062

Other trials in Brazil

Australia1 site

  • Princess Margaret Hospital for Children

    Perth, Western Australia, 6008

Other trials in Australia

About this study

Official title: Treatment of Adrenocortical Tumors With Surgery Plus Lymph Node Dissection and Multiagent Chemotherapy: A Groupwide Phase III Study

This phase III clinical trial is studying how well cisplatin-based chemotherapy and/or surgery works in treating young patients with stage I, stage II, stage III or stage IV adrenocortical cancer. Drugs used in chemotherapy, such as cisplatin, 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. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving it after surgery may kill any tumor cells that remain after surgery.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Describe the outcome of patients with stage I adrenocortical tumor (ACT) treated with surgery alone.

II. Describe the outcome of patients with stage II ACT treated with radical adrenalectomy plus regional retroperitoneal lymph node dissection.

III. Describe the outcome of patients with unresectable or metastatic ACT treated with mitotane and a cisplatin-based chemotherapy regimen.

SECONDARY OBJECTIVES:

  1. Determine the feasibility and complications associated with the use of radical adrenalectomy and regional node dissection (RLND) in these patients.

II. 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.

III. Determine, prospectively, the frequency of tumor spillage during surgery in these patients.

IV. Determine the frequency of lymph node involvement in these patients. V. Compare the incidence and type of germline p53 mutation in non-Brazilian children and children from Southern Brazil.

VI. Characterize the cooperating molecular alterations associated with ACT. VII. Determine the presence of embryonal markers in children with ACT.

OUTLINE:

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 four times 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.

Medical subject headings
Adrenocortical Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CisplatinDrug

    Also called Abiplatin, Blastolem, Briplatin, CDDP

    Given IV

  • Conventional SurgeryProcedure or surgery

    Patients undergo surgery

  • Doxorubicin HydrochlorideDrug

    Also called 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin

    Given IV

  • EtoposideDrug

    Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar

    Given IV

  • FilgrastimBiological

    Also called Filgrastim-aafi, Filgrastim-ayow, G-CSF, Neupogen

    Given subcutaneously

  • MitotaneDrug

    Also called (o,p)-DDD, 1, 1-Dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane, 1-Chloro-2-[2,2-dichloro-1-(4-chlorophenyl)ethyl]benzene, 2, 2-Bis(2-chlorophenyl-4-chlorophenyl)-1,1-dichloroethane

    Given orally

  • PegfilgrastimBiological

    Also called Filgrastim SD-01, filgrastim-SD/01, Fulphila, HSP-130

    Given subcutaneously

Study groups in NCT00304070
Study groupRoleWhat they receive
Stratum I (surgery, observation)ExperimentalPatients undergo primary tumor resection and retroperitoneal lymph node sampling followed by observation. Patients who have undergone prior surgery without nodal sampling undergo observation only.
Receives: Procedure: Conventional Surgery
Stratum II (exploratory surgery, observation)ExperimentalPatients 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.
Receives: Procedure: Conventional Surgery
Stratum III (chemotherapy, surgery)ExperimentalPatients receive combination chemotherapy with filgrastim (G-CSF) for up to 30 weeks (10 courses) followed by mitotane alone for an additional 2 months. Some patients undergo surgery after chemotherapy course 2 or 4. Some patients undergo additional surgery after finishing all chemotherapy.
Receives: Drug: Cisplatin; Procedure: Conventional Surgery; Drug: Doxorubicin Hydrochloride; Drug: Etoposide; Biological: Filgrastim; Drug: Mitotane; Biological: Pegfilgrastim

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Five Year Event-free Survival (EFS)

    The model used for comparison will be an exponential model with a constant failure rate of 0.053 (stratum I), 0.347 (stratum II), 0.602 (stratum III and IV) per year for the first two years and 0 after that. The one-sample one-sided log-rank test comparing the observed data with the hypothesized model (Woolson, 1981) of size 0.05 will be used to assess whether the data are consistent with the target models. Since this test has independent increments, the method of Lan and DeMets will be used to derive the p-values for testing procedure.

    Measured: Up to five years after enrollment

Secondary outcomes (6)

  1. Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

    The proportion of patients assigned to receive chemotherapy that experience CTC Version 4 grade 3 or higher anemia at any time during protocol therapy

    Measured: Up to 182 Days After Enrollment

  2. Complications Associated With Radical Adrenalectomy and RLND

    Any patient who dies because of surgery or has a grade 3 or 4 toxicity possibly, probably or likely related to surgery will be considered as having experienced a surgical complication. The complication rate is estimated as the proportion of evaluable patients that have a complication.

    Measured: Up to 1 month after surgery

  3. Frequency of Lymph Node Involvement by Imaging.

    The number eligible patients who have lymph node involvement by imaging at study enrollment.

    Measured: At study enrollment

  4. Incidence and Type of Germline TP53 Mutations in Non-Brazilian Children and Children From Southern Brazil by Deoxyribonucleic Acid (DNA) Sequencing and Affymetrix Gene Chip Analysis.

    The proportion of patients in each subpopulation are compared.This test is dependent on the number of patients from whom blood can be obtained as well as the frequency of the relevant mutation in each group.

    Measured: At study enrollment

  5. Molecular Alterations and Embryonal Markers in Children With ACT - A43 del33bp Mutation of (Beta)-Catenin.

    The number of eligible patients who have A43 del33bp mutation of (beta)-catenin.

    Measured: Patients who had surgery at time of enrollment.

  6. Frequency of Tumor Spillage at the Time of Tumor Resection

    The number of eligible patients who have surgical resection of the primary tumor and have tumor spillage at the time of resection.

    Measured: Up to one year or while on protocol therapy, whichever is less

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Mar 2006 (estimated)
  2. Study start3 May 2007
  3. Primary completion31 Dec 2015
  4. Study completion30 Jun 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
78 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00304070
Sponsor's protocol ID
ARAR0332
Other IDs
NCI-2009-00413, COG-ARAR0332, ARAR0332, CDR0000467191, ARAR0332, ARAR0332, U10CA180886, U10CA098543
Status last verified
Feb 2024
First submitted
15 Mar 2006
Last updated
28 Feb 2024
Individual data sharing
Yes: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive

Publications

  • Pinto EM, Maxwell KN, Halalsheh H, Phillips A, Powers J, MacFarland S, Walsh MF, Breen K, Formiga MN, Kriwacki R, Nichols KE, Mostafavi R, Wang J, Clay MR, Rodriguez-Galindo C, Ribeiro RC, Zambetti GP. Clinical and Functional Significance of TP53 Exon 4-Intron 4 Splice Junction Variants. Mol Cancer Res. 2022 Feb;20(2):207-216. doi: 10.1158/1541-7786.MCR-21-0583. Epub 2021 Oct 21.

    PubMed 34675114

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cisplatin, Conventional Surgery and Doxorubicin Hydrochloride in people with Stage I Adrenal Cortical Carcinoma AJCC v7 and Stage II Adrenal Cortical Carcinoma AJCC v7, run by Children's Oncology Group at 91 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 91 sites in United States, Canada, Brazil, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Five Year Event-free Survival (EFS) (time frame: Up to five years after enrollment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00304070, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2024.

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