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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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

Brief 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. 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.

Detailed Summary:

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 undergo
Sponsor: Children's Oncology Group

Current Primary Outcome: Event-free survival (EFS) [ Time Frame: At 2 years ]

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.


Original Primary Outcome:

Current Secondary Outcome:

  • 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 ]
  • Toxicity Associated with Chemotherapy using NCI CTCAE v. 4.0 [ Time Frame: Assessed up to 182 days ]
  • Feasibility and Complications Associated with Radical Adrenalectomy and RLND [ Time Frame: Up to 1 month after surgery ]
    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 ]
    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 ]
    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 ]


Original Secondary Outcome:

Information By: Children's Oncology Group

Dates:
Date Received: March 15, 2006
Date Started: September 2006
Date Completion:
Last Updated: March 17, 2016
Last Verified: March 2016