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NCT00304070

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

Completed Phase 3 Results posted Last updated 28 February 2024
What this trial tests

Phase 3 trial testing Cisplatin in Stage I Adrenal Cortical Carcinoma AJCC v7 in 78 participants. Completed in 30 June 2023.

Timeline
3 May 2007
Primary endpoint
31 December 2015
30 June 2023

Quick facts

Lead sponsorChildren's Oncology Group
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment78
Start date3 May 2007
Primary completion31 December 2015
Estimated completion30 June 2023
Sites91 locations across Canada, United States, Australia, Brazil

Drugs / interventions tested

Conditions studied

Sponsor

Children's Oncology Group — full company profile →

Who can join

Under 21, any sex, with Stage I Adrenal Cortical Carcinoma AJCC v7 or Stage II Adrenal Cortical Carcinoma AJCC v7. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Five Year Event-free Survival (EFS) Primary · Up to five years after enrollment

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.

GroupValue95% CI
Stratum 10.860.62 – 0.95
Stratum 20.530.26 – 0.74
Stratum 30.510.33 – 0.66
Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Secondary · Up to 182 Days After Enrollment

The proportion of patients assigned to receive chemotherapy that experience CTC Version 4 grade 3 or higher anemia at any time during protocol therapy

Incidence of Abdominal Infection
GroupValue95% CI
Stratum 31
Incidence of Abdominal Pain
GroupValue95% CI
Stratum 32
Incidence of Acidosis
GroupValue95% CI
Stratum 31
Activated Partial Thromboplastin Time Prolonged
GroupValue95% CI
Stratum 31
Incidence of Adrenal Insufficiency
GroupValue95% CI
Stratum 35
Incidence of Alanine Aminotransferase Increased
GroupValue95% CI
Stratum 32
Incidence of Allergic Reaction
GroupValue95% CI
Stratum 31
Incidence of Anemia
GroupValue95% CI
Stratum 322
Complications Associated With Radical Adrenalectomy and RLND Secondary · 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 is estimated as the proportion of evaluable patients that have a complication.

GroupValue95% CI
All Patients1
Frequency of Lymph Node Involvement by Imaging. Secondary · At study enrollment

The number eligible patients who have lymph node involvement by imaging at study enrollment.

GroupValue95% CI
All Patients71
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. Secondary · At study enrollment

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.

C229R mutation in p53 in Patients from Brazil
GroupValue95% CI
All Patients0
C229R mutation in Patients not from Brazil
GroupValue95% CI
All Patients2
E180K mutation in p53 in Patients from Brazil
GroupValue95% CI
All Patients0
E180K mutation in Patients not from Brazil
GroupValue95% CI
All Patients1
G245C mutation in p53 in Patients from Brazil
GroupValue95% CI
All Patients0
G245C mutation in Patients not from Brazil
GroupValue95% CI
All Patients1
I254T mutation in p53 in Patients from Brazil
GroupValue95% CI
All Patients1
I254T mutation in Patients not from Brazil
GroupValue95% CI
All Patients0
Molecular Alterations and Embryonal Markers in Children With ACT - A43 del33bp Mutation of (Beta)-Catenin. Secondary · Patients who had surgery at time of enrollment.

The number of eligible patients who have A43 del33bp mutation of (beta)-catenin.

children with ACT - wild type (beta)-catenin
GroupValue95% CI
All Patients51
A43 del33bp mutation of (beta)-catenin
GroupValue95% CI
All Patients1
Frequency of Tumor Spillage at the Time of Tumor Resection Secondary · Up to one year or while on protocol therapy, whichever is less

The number of eligible patients who have surgical resection of the primary tumor and have tumor spillage at the time of resection.

GroupValue95% CI
All Patients15

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Stratum 3
Serious: 1/39 (3%)
Deaths:

Serious adverse events (1 terms)

ReactionSystemStratum 3
PneumonitisRespiratory, thoracic and mediastinal disorders
Other adverse events (81 terms — click to expand)

ReactionSystemStratum 3
AnemiaBlood and lymphatic system disorders
Platelet count decreasedInvestigations
Neutrophil count decreasedInvestigations
Febrile neutropeniaBlood and lymphatic system disorders
White blood cell decreasedInvestigations
Hearing impairedEar and labyrinth disorders
HypokalemiaMetabolism and nutrition disorders
AnorexiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
Infections and infestations - Other, specifyInfections and infestations
Mucositis oralGastrointestinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
Adrenal insufficiencyEndocrine disorders
HypophosphatemiaMetabolism and nutrition disorders
HyperkalemiaMetabolism and nutrition disorders
Alanine aminotransferase increasedInvestigations
Cardiac disorders - Other, specifyCardiac disorders
Catheter related infectionInfections and infestations
DehydrationMetabolism and nutrition disorders
HyperglycemiaMetabolism and nutrition disorders
HypocalcemiaMetabolism and nutrition disorders
HypomagnesemiaMetabolism and nutrition disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Lymphocyte count decreasedInvestigations
Abdominal painGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
DiarrheaGastrointestinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
EsophagitisGastrointestinal disorders
Gastrointestinal disorders - Other, specifyGastrointestinal disorders
HypertensionVascular disorders
HypotensionVascular disorders
Left ventricular systolic dysfunctionCardiac disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
SepsisInfections and infestations
Vascular access complicationInjury, poisoning and procedural complications
Abdominal infectionInfections and infestations
AcidosisMetabolism and nutrition disorders
Activated partial thromboplastin time prolongedInvestigations

Most-reported serious reactions: Pneumonitis.

Data from ClinicalTrials.gov NCT00304070 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Prevalence and functional consequence of TP53 mutations in pediatric adrenocortical carcinoma: a children's oncology group study.
    Wasserman JD, Novokmet A, Eichler-Jonsson C, Ribeiro RC, et al · · 2015 · cited 162× · PMID 25584008 · DOI 10.1200/jco.2013.52.6863
  2. Genomic landscape of paediatric adrenocortical tumours.
    Pinto EM, Chen X, Easton J, Finkelstein D, et al · · 2015 · cited 155× · PMID 25743702 · DOI 10.1038/ncomms7302
  3. Treatment of Pediatric Adrenocortical Carcinoma With Surgery, Retroperitoneal Lymph Node Dissection, and Chemotherapy: The Children's Oncology Group ARAR0332 Protocol.
    Rodriguez-Galindo C, Krailo MD, Pinto EM, Pashankar F, et al · · 2021 · cited 60× · PMID 33822640 · DOI 10.1200/jco.20.02871
  4. Identification of Clinical and Biologic Correlates Associated With Outcome in Children With Adrenocortical Tumors Without Germline TP53 Mutations: A St Jude Adrenocortical Tumor Registry and Children's Oncology Group Study.
    Pinto EM, Rodriguez-Galindo C, Pounds SB, Wang L, et al · · 2017 · cited 40× · PMID 29058986 · DOI 10.1200/jco.2017.74.2460
  5. Prognostic Significance of Major Histocompatibility Complex Class II Expression in Pediatric Adrenocortical Tumors: A St. Jude and Children's Oncology Group Study.
    Pinto EM, Rodriguez-Galindo C, Choi JK, Pounds S, et al · · 2016 · cited 25× · PMID 27307598 · DOI 10.1158/1078-0432.ccr-15-2738
  6. Pediatric adrenocortical carcinoma.
    Ilanchezhian M, Varghese DG, Glod JW, Reilly KM, et al · · 2022 · cited 23× · PMID 36387865 · DOI 10.3389/fendo.2022.961650
  7. Clinical and Functional Significance of TP53 Exon 4-Intron 4 Splice Junction Variants.
    Pinto EM, Maxwell KN, Halalsheh H, Phillips A, et al · · 2022 · cited 14× · PMID 34675114 · DOI 10.1158/1541-7786.mcr-21-0583
  8. Is there a role of targeted agents in the management of adrenocortical cancers?
    Saif MW, Fallon B, Syrigos KN. · · 2012 · cited 1× · PMID 23198184 · DOI 10.1155/2012/875764

Verify or expand the search:

Other trials of Cisplatin

Trials testing the same drug.

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