Overview

This trial is active, not recruiting.

Conditions stage i adrenocortical carcinoma, stage ii adrenocortical carcinoma, stage iii adrenocortical carcinoma, stage iv adrenocortical carcinoma
Treatments doxorubicin hydrochloride, conventional surgery, cisplatin, mitotane, etoposide, filgrastim
Phase phase 3
Sponsor Children's Oncology Group
Collaborator National Cancer Institute (NCI)
Start date September 2006
End date December 2015
Trial size 78 participants
Trial identifier NCT00304070, ARAR0332, CDR0000467191, COG-ARAR0332, NCI-2009-00413, U10CA098543

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
conventional surgery surgery, conventional
Patients undergo surgery
(Experimental)
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.
conventional surgery surgery, conventional
Patients undergo surgery
(Experimental)
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.
doxorubicin hydrochloride ADM
Given IV
conventional surgery surgery, conventional
Patients undergo surgery
cisplatin CACP
Given IV
mitotane DDD
Given orally
etoposide EPEG
Given IV
filgrastim G-CSF
Given subcutaneously

Primary Outcomes

Measure
Event-free survival (EFS)
time frame: At 2 years

Secondary Outcomes

Measure
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
Frequency of Tumor Spillage and Lymph Node Involvement
time frame: At upfront surgery
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
Molecular alterations and embryonal markers in children with ACT.
time frame: At time of surgery

Eligibility Criteria

Male or female participants up to 21 years old.

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

Additional Information

Official title Treatment of Adrenocortical Tumors With Surgery Plus Lymph Node Dissection and Multiagent Chemotherapy: A Groupwide Phase III Study
Principal investigator Carlos Rodriguez-Galindo
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in March 2016.
Information provided to ClinicalTrials.gov by Children's Oncology Group.