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

Purpose

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.

Condition	Intervention	Phase
Stage I Adrenocortical Carcinoma Stage II Adrenocortical Carcinoma Stage III Adrenocortical Carcinoma Stage IV Adrenocortical Carcinoma	Drug: doxorubicin hydrochloride Procedure: conventional surgery Drug: cisplatin Drug: mitotane Drug: etoposide Biological: filgrastim	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Treatment of Adrenocortical Tumors With Surgery Plus Lymph Node Dissection and Multiagent Chemotherapy: A Groupwide Phase III Study

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Mitotane Cisplatin Doxorubicin Doxorubicin hydrochloride Etoposide Etoposide phosphate Filgrastim Lenograstim Granulocyte colony-stimulating factor

Genetic and Rare Diseases Information Center resources: Adrenocortical Carcinoma

U.S. FDA Resources

Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:

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.

Secondary Outcome Measures:

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 ]


Enrollment:	78
Study Start Date:	September 2006
Primary Completion Date:	December 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.	Procedure: conventional surgery Patients undergo surgery Other Name: surgery, conventional
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.	Procedure: conventional surgery Patients undergo surgery Other Name: surgery, conventional
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.	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

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Eligibility


Ages Eligible for Study:	up to 21 Years (Child, Adult)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00304070

Show 80 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Carlos Rodriguez-Galindo	Children's Oncology Group

More Information


Responsible Party:	Children's Oncology Group
ClinicalTrials.gov Identifier:	NCT00304070 History of Changes
Other Study ID Numbers:	ARAR0332 NCI-2009-00413 CDR0000467191 COG-ARAR0332 U10CA098543
Study First Received:	March 15, 2006
Last Updated:	March 17, 2016
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:


Carcinoma Adrenocortical Carcinoma Adrenal Cortex Neoplasms Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Adenocarcinoma Adrenal Gland Neoplasms Endocrine Gland Neoplasms Neoplasms by Site Adrenal Cortex Diseases Adrenal Gland Diseases Endocrine System Diseases Liposomal doxorubicin Etoposide phosphate	Cisplatin Doxorubicin Etoposide Mitotane Lenograstim Antineoplastic Agents Antibiotics, Antineoplastic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Phytogenic Adjuvants, Immunologic Immunologic Factors Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 23, 2016