NCT00304070 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2024-02-28

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Five Year Event-free Survival (EFS)

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outcome · POSTED

Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

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outcome · POSTED

Complications Associated With Radical Adrenalectomy and RLND

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outcome · POSTED

Frequency of Lymph Node Involvement by Imaging.

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outcome · POSTED

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.

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outcome · POSTED

Molecular Alterations and Embryonal Markers in Children With ACT - A43 del33bp Mutation of (Beta)-Catenin.

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outcome · POSTED

Frequency of Tumor Spillage at the Time of Tumor Resection

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility 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
healthy Volunteers: false
maximum Age: 21 Years
sex: ALL
std Ages: CHILD
ADULT

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Procedure: Conventional Surgery
label
Stratum I (surgery, observation)
type
EXPERIMENTAL
description
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.
intervention Names
Procedure: Conventional Surgery
label
Stratum II (exploratory surgery, observation)
type
EXPERIMENTAL
description
Patients receive combination chemotherapy with filgrastim (G-CSF) for up to 30 weeks (10 courses) followed by mitotane alone for an additional 2 months. Some patients undergo surgery after chemotherapy course 2 or 4. Some patients undergo additional surgery after finishing all chemotherapy.
intervention Names
Drug: Cisplatin
Procedure: Conventional Surgery
Drug: Doxorubicin Hydrochloride
Drug: Etoposide
Biological: Filgrastim
Drug: Mitotane
Biological: Pegfilgrastim
label
Stratum III (chemotherapy, surgery)
type
EXPERIMENTAL

interventions

arm Group Labels
Stratum III (chemotherapy, surgery)
description
Given IV
name
Cisplatin
other Names
Abiplatin
Blastolem
Briplatin
CDDP
Cis-diammine-dichloroplatinum
Cis-diamminedichloridoplatinum
Cis-diamminedichloro Platinum (II)
Cis-diamminedichloroplatinum
Cis-dichloroammine Platinum (II)
Cis-platinous Diamine Dichloride
Cis-platinum
Cis-platinum II
type
DRUG
arm Group Labels
Stratum I (surgery, observation)
Stratum II (exploratory surgery, observation)
Stratum III (chemotherapy, surgery)
description
Patients undergo surgery
name
Conventional Surgery
type
PROCEDURE
arm Group Labels
Stratum III (chemotherapy, surgery)
description
Given IV
name
Doxorubicin Hydrochloride
other Names
5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)
ADM
Adriacin
Adriamycin
Adriamycin Hydrochloride
Adriamycin PFS
Adriamycin RDF
ADRIAMYCIN, HYDROCHLORIDE
Adriamycine
Adriblastina
Adriblastine
Adrimedac
type
DRUG
arm Group Labels
Stratum III (chemotherapy, surgery)
description
Given IV
name
Etoposide
other Names
Demethyl Epipodophyllotoxin Ethylidine Glucoside
EPEG
Lastet
Toposar
Vepesid
VP 16
VP 16-213
VP-16
VP-16-213
VP16
type
DRUG
arm Group Labels
Stratum III (chemotherapy, surgery)
description
Given subcutaneously
name
Filgrastim
other Names
Filgrastim-aafi
Filgrastim-ayow
G-CSF
Neupogen
Nivestym
r-metHuG-CSF
Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
Releuko
rG-CSF
Tevagrastim
type
BIOLOGICAL
arm Group Labels
Stratum III (chemotherapy, surgery)
description
Given orally
name
Mitotane
other Names
(o,p)-DDD
1, 1-Dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane
1-Chloro-2-[2,2-dichloro-1-(4-chlorophenyl)ethyl]benzene
2, 2-Bis(2-chlorophenyl-4-chlorophenyl)-1,1-dichloroethane
2, 4'-Dichlorodiphenyldichloroethane
CB 313
CB-313
Chloditan
Chlodithane
DDD
Ethane, 2-(o-chlorophenyl)-2-(p-chlorophenyl)-1,1-dichloro-
Khloditan
type
DRUG
arm Group Labels
Stratum III (chemotherapy, surgery)
description
Given subcutaneously
name
Pegfilgrastim
other Names
Filgrastim SD-01
filgrastim-SD/01
Fulphila
HSP-130
Jinyouli
Neulasta
Neulastim
Nyvepria
PEG-filgrastim
Pegcyte
Pegfilgrastim Biosimilar HSP-130
Pegfilgrastim Biosimilar Nyvepria
type
BIOLOGICAL

Study design

allocation

NON_RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 78
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

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.
measure
Five Year Event-free Survival (EFS)
time Frame
Up to five years after enrollment

secondary Outcomes

description
The proportion of patients assigned to receive chemotherapy that experience CTC Version 4 grade 3 or higher anemia at any time during protocol therapy
measure
Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
time Frame
Up to 182 Days After Enrollment
description
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 is estimated as the proportion of evaluable patients that have a complication.
measure
Complications Associated With Radical Adrenalectomy and RLND
time Frame
Up to 1 month after surgery
description
The number eligible patients who have lymph node involvement by imaging at study enrollment.
measure
Frequency of Lymph Node Involvement by Imaging.
time Frame
At study enrollment
description
The proportion of patients in each subpopulation are compared.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.
measure
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 study enrollment
description
The number of eligible patients who have A43 del33bp mutation of (beta)-catenin.
measure
Molecular Alterations and Embryonal Markers in Children With ACT - A43 del33bp Mutation of (Beta)-Catenin.
time Frame
Patients who had surgery at time of enrollment.
description
The number of eligible patients who have surgical resection of the primary tumor and have tumor spillage at the time of resection.
measure
Frequency of Tumor Spillage at the Time of Tumor Resection
time Frame
Up to one year or while on protocol therapy, whichever is less

Full study description

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 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 SURGERY: 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.

Source references

references

citation
Pinto EM, Maxwell KN, Halalsheh H, Phillips A, Powers J, MacFarland S, Walsh MF, Breen K, Formiga MN, Kriwacki R, Nichols KE, Mostafavi R, Wang J, Clay MR, Rodriguez-Galindo C, Ribeiro RC, Zambetti GP. Clinical and Functional Significance of TP53 Exon 4-Intron 4 Splice Junction Variants. Mol Cancer Res. 2022 Feb;20(2):207-216. doi: 10.1158/1541-7786.MCR-21-0583. Epub 2021 Oct 21.
pmid
34675114
type
DERIVED