NCT00053352 · CITED IN SOURCE DOCUMENTS

Surgery and Combination Chemotherapy in Treating Children With Extracranial Germ Cell Tumors

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: 2021-07-13

This phase III trial is studying surgery followed by combination chemotherapy to see how well it works in treating children with germ cell tumors that are not located in the head. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug, and giving them after surgery, may kill any remaining tumor cells following surgery. It is not yet known whether combination chemotherapy is effective in decreasing the recurrence of childhood germ cell tumors.

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

→

baseline

Baseline characteristics

→

outcome · POSTED

Event-Free Survival (EFS)

→

outcome · POSTED

Overall Survival (OS)

→

outcome · POSTED

Days Hospitalized for Patients Who Receive Chemotherapy

→

outcome · POSTED

Toxicity Associated With Chemotherapy: Grade 3 or Higher. Toxicity as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

eligibility Criteria: Inclusion Criteria: * Extracranial germ cell tumor that contains 1 of the following malignant histologies: NOTE: Mixed germ cell tumors that include mature/immature teratoma are eligible provided 1 of the 3 histologies listed above is also present in the tumor. * Yolk sac tumor * Embryonal carcinoma * Choriocarcinoma * Low-risk disease (closed to accrual as of 01/20/10) * Stage I gonadal tumors (ovarian and testicular) * Must have undergone complete surgical and radiologic staging to exclude the possibility of \> stage I disease * Intermediate-risk disease * Stage II, III, or IV malignant testicular GCT * Stage II or III malignant ovarian GCT * Stage I or II malignant extragonadal GCT * Previously stage I gonadal patients who have relapsed on the low-risk (observation) stratum of this study(closed to accrual as of 01/20/10) * Patients with immature teratoma or mature teratoma who relapse with a malignant component * No patients with any of the following diagnoses: * Stage IV ovarian and stage III-IV extragonadal GCT * Intracranial GCT * Pure mature or immature teratoma, pure dysgerminoma, or seminoma * Patients with a non-germ cell component in their GCT (e.g., primitive neuroectodermal tumors or rhabdomyosarcoma) * Alpha-fetoprotein and beta human chorionic gonadotropin tumor markers known * If \> 5 days have elapsed from the time of obtaining original markers, tumor markers must be repeated before enrollment of low-risk patients and before initiating therapy in intermediate-risk patients (the results of the repeated tumor markers do not have to be known at the time of study enrollment) * Must be enrolled within 6 weeks of original diagnostic surgery * Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR a serum creatinine based on age/gender as follows: * ≤ 0.4 mg/dL (for patients 1 to 5 months of age) * ≤ 0.5 mg/dL (for patients 6 to 11 months of age) * ≤ 0.6 mg/dL (for patients 1 year of age) * ≤ 0.8 mg/dL (for patients 2 to 5 years of age) * ≤ 1.0 mg/dL (for patients 6 to 9 years of age) * ≤ 1.2 mg/dL (for patients 10 to 12 years of age) * ≤ 1.4 mg/dL (for female patients ≥ 13 years of age) * ≤ 1.5 mg/dL (for male patients 13 to 15 years of age) * ≤ 1.7 mg/dL (for male patients ≥ 16 years of age) * No prior chemotherapy * No prior radiotherapy
healthy Volunteers: false
maximum Age: 21 Years
sex: ALL
std Ages: CHILD
ADULT

Treatment arms and interventions

arm Groups

description
Patients enrolled with gonadal tumors of stage II or greater or extragonadal tumors of any stage receive cisplatin IV over 90 minutes \& etoposide IV over 90 minutes days 1-3 and bleomycin sulfate IV over ≥ 10 minutes day 1. Treatment repeats every 3 weeks, 3 courses (weeks 0,3 \& 6). After completion of compressed induction chemotherapy, patients with no change in disease status or disease progression are removed from study. Patients with no evidence of disease receive no further therapy. Patients with a partial response or abnormal tumor markers proceed to conventional surgery (second-look) and/or 3 more courses of compressed consolidation chemotherapy. After surgery, patients with pathologic complete response and have normal tumor markers receive no further therapy. Patients who remain with a partial response after surgery receive compressed consolidation chemotherapy. Patients receive cisplatin, etoposide, and bleomycin as induction chemotherapy in weeks 10,13, \& 16.
intervention Names
Procedure: conventional surgery
Drug: cisplatin
Drug: etoposide
Biological: bleomycin sulfate
Other: laboratory biomarker analysis
label
Arm I
type
EXPERIMENTAL
description
Patients who are enrolled with stage I gonadal tumors receive no further anticancer therapy until evidence of tumor recurrence or the diagnosis of a second malignant neoplasm. Observation only for recurrence or development of an SMN
label
Arm 2
type
NO_INTERVENTION

interventions

arm Group Labels
Arm I
name
conventional surgery
other Names
surgery, conventional
type
PROCEDURE
arm Group Labels
Arm I
description
Given IV
name
cisplatin
other Names
CACP
CDDP
CPDD
DDP
type
DRUG
arm Group Labels
Arm I
description
Given IV
name
etoposide
other Names
EPEG
VP-16
VP-16-213
type
DRUG
arm Group Labels
Arm I
description
Given IV
name
bleomycin sulfate
other Names
Blenoxane
BLEO
BLM
type
BIOLOGICAL
arm Group Labels
Arm I
description
Correlative studies
name
laboratory biomarker analysis
type
OTHER

Study design

allocation

NON_RANDOMIZED

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 302
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Proportion of patients event free at 3 years following enrollment. Event-free survival is not a primary outcome measure for Arm 2 patients.
measure
Event-Free Survival (EFS)
time Frame
3 Years after enrollment
description
Percentage probability of being alive at 3 years following enrollment.
measure
Overall Survival (OS)
time Frame
3 Years after enrollment

secondary Outcomes

description
Calculated to quantify the treatment cost associated with this regimen.
measure
Days Hospitalized for Patients Who Receive Chemotherapy
time Frame
Up to 126 days after the start of chemotherapy
description
The number of patients assigned to receive chemotherapy that experience CTC Version 4 grade 3 or higher at any time during protocol therapy
measure
Toxicity Associated With Chemotherapy: Grade 3 or Higher. Toxicity as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0
time Frame
Up to 126 days after the start of chemotherapy

Full study description

brief Summary: This phase III trial is studying surgery followed by combination chemotherapy to see how well it works in treating children with germ cell tumors that are not located in the head. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug, and giving them after surgery, may kill any remaining tumor cells following surgery. It is not yet known whether combination chemotherapy is effective in decreasing the recurrence of childhood germ cell tumors.
detailed Description: OBJECTIVES: I. Determine whether children with newly diagnosed low- or intermediate-risk extracranial germ cell tumors (GCTs) can maintain a 3-year event-free survival of at least 92% (for intermediate-risk tumors only) and overall survival of at least 95% (both low-risk and intermediate-risk tumors) after treatment with surgery followed by compressed cisplatin, etoposide, and bleomycin (low-risk disease closed to accrual as of 01/20/10). II. Determine the percentage of patients with stage I ovarian or stage I testicular GCTs for whom chemotherapy can be eliminated. III. Determine the percentage of intermediate-risk patients who require only 3 courses of therapy. IV. Determine the acute toxic effects of compressed therapy in these patients. V. Determine the long-term sequelae in patients treated with this regimen. VI. Determine the number of hospital days and total drug doses required for patients treated with compressed therapy. VII. Compare the number of protocol-directed treatment days used in CCG-8882 vs the number of treatment days used in this study. VIII. Determine the cytogenetic and molecular genetic features in patients treated with this regimen. OUTLINE: Patients are stratified according to disease risk (low vs intermediate). SURGERY: Patients undergo surgical resection. Low-risk disease: Patients with gonadal primaries and no evidence of disease after surgery undergo monitoring for disease progression. Patients who remain disease free receive no further treatment. Patients who have disease progression after surgery receive compressed induction chemotherapy. (closed to accrual as of 01/20/2010) Intermediate-risk disease: After surgery, patients proceed to compressed induction chemotherapy. COMPRESSED INDUCTION CHEMOTHERAPY: Patients receive cisplatin IV over 90 minutes and etoposide IV over 90 minutes on days 1-3 and bleomycin IV over ≥ 10 minutes on day 1. Treatment repeats every 3 weeks for 3 courses (weeks 0, 3, and 6). After completion of compressed induction chemotherapy, patients who have no change in disease status or disease progression are removed from study. Patients with no evidence of disease receive no further therapy. Patients with a partial response or who have abnormal tumor markers proceed to second-look surgery and/or 3 more courses of compressed consolidation chemotherapy. SECOND-LOOK SURGERY: Patients undergo surgical resection of residual tumor. After surgery, patients who are in pathologic complete response and have normal tumor markers receive no further therapy. Patients who remain with a partial response after surgery receive compressed consolidation chemotherapy. COMPRESSED CONSOLIDATION CHEMOTHERAPY: Patients receive cisplatin, etoposide, and bleomycin as in induction chemotherapy in weeks 10, 13, and 16. Patients are followed up monthly for 6 months, every 3 months for 18 months, and then annually for up to 10 years.

Source references

references

citation
O'Neill AF, Xia C, Krailo MD, Shaikh F, Pashankar FD, Billmire DF, Olson TA, Amatruda JF, Villaluna D, Huang L, Malogolowkin M, Rodriguez-Galindo C, Frazier AL. alpha-Fetoprotein as a predictor of outcome for children with germ cell tumors: A report from the Malignant Germ Cell International Consortium. Cancer. 2019 Oct 15;125(20):3649-3656. doi: 10.1002/cncr.32363. Epub 2019 Jul 29.
pmid
31355926
type
DERIVED