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


Phase 3
N/A
21 Years
Open (Enrolling)
Both
Stage I Adrenocortical Carcinoma, Stage II Adrenocortical Carcinoma, Stage III Adrenocortical Carcinoma, Stage IV Adrenocortical Carcinoma

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Trial Information

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


PRIMARY OBJECTIVES:

I. 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:

I. 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 SURGEY: 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.


Inclusion Criteria:



- 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

- 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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Event-free survival (EFS)

Outcome Description:

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.

Outcome Time Frame:

At 2 years

Safety Issue:

No

Principal Investigator

Carlos Rodriguez-Galindo

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

ARAR0332

NCT ID:

NCT00304070

Start Date:

September 2006

Completion Date:

Related Keywords:

  • Stage I Adrenocortical Carcinoma
  • Stage II Adrenocortical Carcinoma
  • Stage III Adrenocortical Carcinoma
  • Stage IV Adrenocortical Carcinoma
  • Adrenal Cortex Neoplasms
  • Carcinoma
  • Adrenocortical Carcinoma

Name

Location

Baylor College of MedicineHouston, Texas  77030
Cleveland Clinic FoundationCleveland, Ohio  44195
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
Washington University School of MedicineSaint Louis, Missouri  63110
Tripler Army Medical CenterHonolulu, Hawaii  96859-5000
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
Midwest Children's Cancer CenterMilwaukee, Wisconsin  53226
Sinai Hospital of BaltimoreBaltimore, Maryland  21225
Geisinger Medical CenterDanville, Pennsylvania  17822-0001
Newark Beth Israel Medical CenterNewark, New Jersey  07112
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
Hackensack University Medical CenterHackensack, New Jersey  07601
Children's Hospital Los AngelesLos Angeles, California  90027-0700
Children's National Medical CenterWashington, District of Columbia  20010-2970
All Children's HospitalSt. Petersburg, Florida  33701
Saint Jude Midwest AffiliatePeoria, Illinois  61637
University of Oklahoma Health Sciences CenterOklahoma City, Oklahoma  73104
St. Jude Children's Research HospitalMemphis, Tennessee  38105-2794
Driscoll Children's HospitalCorpus Christi, Texas  78466
Southern California Permanente Medical GroupDowney, California  90242
Children's Hospital Central CaliforniaMadera, California  93638-8762
Kosair Children's HospitalLouisville, Kentucky  40202-3830
Children's Hospital Medical Center of AkronAkron, Ohio  44308
Overlook HospitalSummit, New Jersey  07902-0220
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Methodist Children's Hospital of South TexasSan Antonio, Texas  78229-3993
Primary Children's Medical CenterSalt Lake City, Utah  84113-1100
Nationwide Children's HospitalColumbus, Ohio  43205-2696
Children's Hospital of Pittsburgh of UPMCPittsburgh, Pennsylvania  15213
Lee Memorial Health SystemFort Myers, Florida  33902
University of VirginiaCharlottesville, Virginia  22908
University of Alabama at BirminghamBirmingham, Alabama  35294-3300
Children's Hospital of AlabamaBirmingham, Alabama  35233
Connecticut Children's Medical CenterHartford, Connecticut  06106
University of North CarolinaChapel Hill, North Carolina  27599
Duke University Medical CenterDurham, North Carolina  27710
University of RochesterRochester, New York  14642
Wayne State UniversityDetroit, Michigan  48202
BI-LO Charities Children's Cancer CenterGreenville, South Carolina  29605
University of Arizona Health Sciences CenterTucson, Arizona  85724
University Of VermontBurlington,, Vermont  05403
University of Texas Southwestern Medical CenterDallas, Texas  
University of KentuckyLexington, Kentucky  40536-0098
Tulane University Health Sciences CenterNew Orleans, Louisiana  70112
University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470
Seattle Children's HospitalSeattle, Washington  98105
Childrens Memorial HospitalChicago, Illinois  60614
Michigan State University - Breslin Cancer CenterEast Lansing, Michigan  48824-1313
Nevada Cancer Research Foundation CCOPLas Vegas, Nevada  89106
Cook Children's Medical CenterFort Worth, Texas  76104
West Virginia University CharlestonCharleston, West Virginia  25304
The Children's Medical Center of DaytonDayton, Ohio  45404
University of Miami Miller School of Medicine-Sylvester Cancer CenterMiami, Florida  33136
University of Minnesota Medical Center-FairviewMinneapolis, Minnesota  55455
Southern Illinois UniversitySpringfield, Illinois  62702
Walter Reed National Military Medical CenterBethesda, Maryland  20889
Riley Hospital for ChildrenIndianapolis, Indiana  46202
Miller Children's HospitalLong Beach, California  90806
Childrens Hospital of Orange CountyOrange, California  92868-3874
Saint Joseph Children's Hospital of TampaTampa, Florida  33607
The Childrens Mercy HospitalKansas City, Missouri  64108
Rainbow Babies and Childrens HospitalCleveland, Ohio  44106
Palmetto Health RichlandColumbia, South Carolina  29203
Childrens Hospital-King's DaughtersNorfolk, Virginia  23507
Children's Hospital ColoradoAurora, Colorado  80045
Lucile Packard Children's Hospital Stanford UniversityPalo Alto, California  94304
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical CenterDenver, Colorado  80218
Greenville Cancer Treatment CenterGreenville, South Carolina  29605