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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00304070
First received: March 15, 2006
Last updated: August 5, 2014
Last verified: August 2014

March 15, 2006
August 5, 2014
September 2006
September 2015   (final data collection date for primary outcome measure)
Event-free survival (EFS) [ Time Frame: At 2 years ] [ Designated as safety issue: No ]
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.
Not Provided
Complete list of historical versions of study NCT00304070 on ClinicalTrials.gov Archive Site
  • Toxicity Associated with mitotane using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Weekly for up to 4 weeks ] [ Designated as safety issue: Yes ]
  • Toxicity Associated with Chemotherapy using NCI CTCAE v. 4.0 [ Time Frame: Assessed up to 182 days ] [ Designated as safety issue: No ]
  • Feasibility and Complications Associated with Radical Adrenalectomy and RLND [ Time Frame: Up to 1 month after surgery ] [ Designated as safety issue: Yes ]
    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 will be estimated as the proportion of evaluable patients that have a complication.
  • Frequency of Tumor Spillage and Lymph Node Involvement [ Time Frame: At upfront surgery ] [ Designated as safety issue: No ]
    The percent of patients who have tumor spillage, and the associated 95% confidence interval, will be the indices of this outcome. Similar considerations apply for the determination of the proportion of patients with lymph node involvement.
  • 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 [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    The proportion of patients in each subpopulation will be compared using the exact conditional test of proportions of size 0.05. The power of 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.
  • Molecular alterations and embryonal markers in children with ACT. [ Time Frame: At time of surgery ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Cisplatin-Based Chemotherapy and/or Surgery in Treating Young Patients With Adrenocortical Tumor
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.

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.

Interventional
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Stage I Adrenocortical Carcinoma
  • Stage II Adrenocortical Carcinoma
  • Stage III Adrenocortical Carcinoma
  • Stage IV Adrenocortical Carcinoma
  • Drug: doxorubicin hydrochloride
    Given IV
    Other Names:
    • ADM
    • ADR
    • Adria
    • Adriamycin PFS
    • Adriamycin RDF
  • Procedure: conventional surgery
    Patients undergo surgery
    Other Name: surgery, conventional
  • Drug: cisplatin
    Given IV
    Other Names:
    • CACP
    • CDDP
    • CPDD
    • DDP
  • Drug: mitotane
    Given orally
    Other Names:
    • DDD
    • Lysodren
    • o,p'-DDD
  • Drug: etoposide
    Given IV
    Other Names:
    • EPEG
    • VP-16
    • VP-16-213
  • Biological: filgrastim
    Given subcutaneously
    Other Names:
    • G-CSF
    • Neupogen
  • Experimental: Stratum I (surgery, observation)
    Patients undergo conventional surgery (primary tumor resection and retroperitoneal lymph node sampling) followed by observation. Patients who have undergone prior surgery without nodal sampling undergo observation only.
    Intervention: Procedure: conventional surgery
  • Experimental: Stratum II (exploratory surgery, observation)
    Patients undergo conventional surgery (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.
    Intervention: Procedure: conventional surgery
  • Experimental: Stratum III (chemotherapy, surgery)
    Patients receive combination chemotherapy with a total of 8 cycles of chemotherapy with cisplatin, etoposide and doxorubicin hydrochloride, filgrastim (G-CSF). The first 2 to 4 cycles are called the induction phase, followed by mitotane alone for an additional 2 months. Some patients undergo conventional surgery after chemotherapy course 2 or 4. Some patients undergo additional conventional surgery after finishing all chemotherapy.
    Interventions:
    • Drug: doxorubicin hydrochloride
    • Procedure: conventional surgery
    • Drug: cisplatin
    • Drug: mitotane
    • Drug: etoposide
    • Biological: filgrastim
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
78
Not Provided
September 2015   (final data collection date for primary outcome measure)

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
Both
up to 21 Years
No
Contact information is only displayed when the study is recruiting subjects
Canada,   United States,   Brazil,   Australia
 
NCT00304070
ARAR0332, NCI-2009-00413, CDR0000467191, COG-ARAR0332, U10CA098543
Not Provided
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Carlos Rodriguez-Galindo Children's Oncology Group
Children's Oncology Group
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP