Stage I Adrenal Cortical Carcinoma AJCC v7, Stage II Adrenal Cortical Carcinoma AJCC v7, Stage III Adrenal Cortical Carcinoma AJCC v7, Stage IV Adrenal Cortical Carcinoma AJCC v7
Conditions
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.
Interventions
DRUGCisplatin
Given IV
PROCEDUREConventional Surgery
Patients undergo surgery
DRUGDoxorubicin Hydrochloride
Given IV
DRUGEtoposide
Given IV
BIOLOGICALFilgrastim
Given subcutaneously
DRUGMitotane
Given orally
BIOLOGICALPegfilgrastim
Given subcutaneously
Sponsors
National Cancer Institute (NCI)
Children's Oncology Group
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 21 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Five Year Event-free Survival (EFS) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complications Associated With Radical Adrenalectomy and RLND | 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. |
| Frequency of Lymph Node Involvement by Imaging. | At study enrollment | The number eligible patients who have lymph node involvement by imaging at study enrollment. |
| Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | 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 |
| Molecular Alterations and Embryonal Markers in Children With ACT - A43 del33bp Mutation of (Beta)-Catenin. | Patients who had surgery at time of enrollment. | The number of eligible patients who have A43 del33bp mutation of (beta)-catenin. |
| Frequency of Tumor Spillage at the Time of Tumor Resection | 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. |
| 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. | 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. |
Countries
Australia, Brazil, Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Stratum 1 Stage I Disease (surgery, observation) | 24 |
| Stratum 2 Stage II Disease (surgery, observation) | 15 |
| Stratum 3 Stage III OR IV Disease (chemotherapy) | 39 |
| Total | 78 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 3 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 3 |
| Overall Study | Progressive Disease | 3 | 7 | 4 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Stratum 1 | Stratum 2 | Stratum 3 | Total |
|---|---|---|---|---|
| Age, Continuous | 2 years | 3 years | 7 years | 5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 7 Participants | 16 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 8 Participants | 20 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 0 Participants | 7 Participants | 13 Participants |
| Race (NIH/OMB) White | 15 Participants | 12 Participants | 28 Participants | 55 Participants |
| Region of Enrollment Brazil | 12 participants | 6 participants | 12 participants | 30 participants |
| Region of Enrollment Canada | 0 participants | 2 participants | 3 participants | 5 participants |
| Region of Enrollment United States | 12 participants | 7 participants | 24 participants | 43 participants |
| Sex: Female, Male Female | 14 Participants | 10 Participants | 27 Participants | 51 Participants |
| Sex: Female, Male Male | 10 Participants | 5 Participants | 12 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 38 / 39 |
| serious Total, serious adverse events | 1 / 39 |
Outcome results
Primary
Five Year Event-free Survival (EFS)
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.
Time frame: Up to five years after enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stratum 1 | Five Year Event-free Survival (EFS) | 0.86 Estimated probability five year EFS |
| Stratum 2 | Five Year Event-free Survival (EFS) | 0.53 Estimated probability five year EFS |
| Stratum 3 | Five Year Event-free Survival (EFS) | 0.51 Estimated probability five year EFS |
Comparison: We will test the 2-year EFS is 90% using the asymptotic distribution of the complementary log-log distribution of the Kaplan-Meier (KM) estimate.p-value: 0.442-year KM estimate
Comparison: We will test the 2-year EFS is 50% using the asymptotic distribution of the complementary log-log distribution of the Kaplan-Meier (KM) estimate.p-value: 0.42-year KM estimate
Comparison: We will test the 2-year EFS is 15% using the asymptotic distribution of the complementary log-log distribution of the Kaplan-Meier (KM) estimate.p-value: 0.000008532-year KM estimate
Secondary
Complications Associated With Radical Adrenalectomy and RLND
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.
Time frame: Up to 1 month after surgery
Population: Sixty-nine eligible patients received surgery of the primary tumor site or RPLND. Complication rates were considered over the entire population regardless of Arm/Group assignment. One patient had grade 3 abdominal pain attributed to surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stratum 1 | Complications Associated With Radical Adrenalectomy and RLND | 1 participants |
Secondary
Frequency of Lymph Node Involvement by Imaging.
The number eligible patients who have lymph node involvement by imaging at study enrollment.
Time frame: At study enrollment
Population: Seventy-five eligible patients had tumor imaging done at the time of study enrollment and evaluated for the presence of lymph node involvement
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stratum 1 | Frequency of Lymph Node Involvement by Imaging. | 71 Participants |
Secondary
Frequency of Tumor Spillage at the Time of Tumor Resection
The number of eligible patients who have surgical resection of the primary tumor and have tumor spillage at the time of resection.
Time frame: Up to one year or while on protocol therapy, whichever is less
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stratum 1 | Frequency of Tumor Spillage at the Time of Tumor Resection | 15 Participants |
Secondary
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.
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.
Time frame: At study enrollment
Population: 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 (Number of patients from Brazil: 23. Number of patients not from Brazil: 31)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stratum 1 | 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. | C229R mutation in p53 in Patients from Brazil | 0 participants |
| Stratum 1 | 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. | C229R mutation in Patients not from Brazil | 2 participants |
| Stratum 1 | 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. | E180K mutation in p53 in Patients from Brazil | 0 participants |
| Stratum 1 | 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. | E180K mutation in Patients not from Brazil | 1 participants |
| Stratum 1 | 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. | G245C mutation in p53 in Patients from Brazil | 0 participants |
| Stratum 1 | 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. | G245C mutation in Patients not from Brazil | 1 participants |
| Stratum 1 | 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. | I254T mutation in p53 in Patients from Brazil | 1 participants |
| Stratum 1 | 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. | I254T mutation in Patients not from Brazil | 0 participants |
| Stratum 1 | 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. | L265Q mutation in p53 in Patients from Brazil | 0 participants |
| Stratum 1 | 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. | L265Q mutation in Patients not from Brazil | 1 participants |
| Stratum 1 | 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. | P47S mutation in p53 in Patients from Brazil | 0 participants |
| Stratum 1 | 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. | P47S mutation in Patients not from Brazil | 1 participants |
| Stratum 1 | 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. | Q52fs mutation in p53 in Patients from Brazil | 0 participants |
| Stratum 1 | 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. | Q52fs mutation in Patients not from Brazil | 1 participants |
| Stratum 1 | 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. | R158L mutation in Patients from Brazil | 0 participants |
| Stratum 1 | 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. | R158L mutation in Patients not from Brazil | 1 participants |
| Stratum 1 | 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. | G245S mutation in Patients from Brazil | 0 participants |
| Stratum 1 | 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. | G245S mutation in Patients not from Brazil | 1 participants |
| Stratum 1 | 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. | R213P mutation in p53 in Patients from Brazil | 0 participants |
| Stratum 1 | 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. | R213P mutation in Patients not from Brazil | 1 participants |
| Stratum 1 | 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. | R248L mutation in Patients from Brazil | 0 participants |
| Stratum 1 | 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. | R248L mutation in Patients not from Brazil | 1 participants |
| Stratum 1 | 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. | R282W mutation in p53 in Patients from Brazil | 0 participants |
| Stratum 1 | 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. | R282W mutation in p53 in Patients not from Brazil | 1 participants |
| Stratum 1 | 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. | R283H mutation in p53 in Patients from Brazil | 0 participants |
| Stratum 1 | 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. | R283H mutation in p53 in Patients not from Brazil | 31 participants |
| Stratum 1 | 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. | R337H mutation in p53 in Patients from Brazil | 20 participants |
| Stratum 1 | 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. | R337H mutation in p53 in Patients not from Brazil | 0 participants |
| Stratum 1 | 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. | R342X mutation in p53 in Patients from Brazil | 0 participants |
| Stratum 1 | 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. | R342X mutation in p53 in Patients not from Brazil | 1 participants |
| Stratum 1 | 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. | T125T c375G>A muation in p53 in Pts from Brazil | 1 participants |
| Stratum 1 | 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. | T125T c375G>A mutation in p53 in pts not from Braz | 1 participants |
| Stratum 1 | 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. | T125T splice in DBD in pts from Brazil | 0 participants |
| Stratum 1 | 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. | T125T splice in DBD in pts not from Brazil | 1 participants |
| Stratum 1 | 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. | wild type p53 in Patients from Brazil | 1 participants |
| Stratum 1 | 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. | wild type p53 in Patients not from Brazil | 16 participants |
Secondary
Molecular Alterations and Embryonal Markers in Children With ACT - A43 del33bp Mutation of (Beta)-Catenin.
The number of eligible patients who have A43 del33bp mutation of (beta)-catenin.
Time frame: Patients who had surgery at time of enrollment.
Population: Fifty-eight eligible patients had material examined for the presence of (beta)-catenin mutations.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Stratum 1 | Molecular Alterations and Embryonal Markers in Children With ACT - A43 del33bp Mutation of (Beta)-Catenin. | children with ACT - wild type (beta)-catenin | 51 Participants |
| Stratum 1 | Molecular Alterations and Embryonal Markers in Children With ACT - A43 del33bp Mutation of (Beta)-Catenin. | A43 del33bp mutation of (beta)-catenin | 1 Participants |
Secondary
Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
The proportion of patients assigned to receive chemotherapy that experience CTC Version 4 grade 3 or higher anemia at any time during protocol therapy
Time frame: Up to 182 Days After Enrollment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Abdominal Pain | 2 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Abdominal Infection | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Acidosis | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Activated Partial Thromboplastin Time Prolonged | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Adrenal Insufficiency | 5 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Alanine Aminotransferase Increased | 2 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Allergic Reaction | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Anemia | 22 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Anorexia | 7 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Aspartate Aminotransferase Increased | 2 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Blood Bilirubin Increased | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Cardiac Disorders - Other, Specify | 2 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Catheter Related Infection | 3 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Colitis | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Confusion | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Dehydration | 3 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Depressed Level of Consciousness | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Diarrhea | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Dyspnea | 2 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Enterocolitis Infectious | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Esophagitis | 2 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Febrile Neutropenia | 16 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Fever | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Gastrointestinal Disorders - Other, S | 2 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Generalized Muscle Weakness | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of GGT Increased | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Hearing Impaired | 6 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Heart Failure | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Hyperglycemia | 3 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Hyperkalemia | 3 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Hypertension | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Hypocalcemia | 3 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Hypoglycemia | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Hypokalemia | 9 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Hypomagnesemia | 2 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Hyponatremia | 7 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Hypophosphatemia | 4 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Hypotension | 2 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Hypoxia | 3 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Infections and Infestations - Other, | 7 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of INR Increased | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Left Ventricular Systolic Dysfunction | 2 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Lung Infection | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Lymphocyte Count Decreased | 2 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Toxicity Associated with Mitotane | 4 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Mucositis Oral | 6 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Nausea | 5 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Neutrophil Count Decreased | 20 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Obstruction Gastric | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Pain | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Peripheral Motor Neuropathy | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Peripheral Sensory Neuropathy | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Pharyngitis | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Platelet Count Decreased | 20 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Pneumonitis | 3 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Premature Menopause | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Rash Maculo-papular | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Sepsis | 2 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Skin Infection | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Sore Throat | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Upper Respiratory Infection | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Urinary Tract Infection | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Vascular Access Complication | 2 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Ventricular Arrhythmia | 1 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Vomiting | 5 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of White Blood Cell Decreased | 16 participants |
| Stratum 1 | Toxicity Associated With Chemotherapy Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Incidence of Wound Infection | 1 participants |