Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Endodermal Sinus Tumor

Teratoma

Testicular Neoplasms

Carcinoma, Embryonal

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Neoplasms, Germ Cell and Embryonal

Germinoma

Ovarian Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

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Female Urogenital Diseases

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Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

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Gonadal Disorders

Genital Neoplasms, Male

Genital Diseases, Male

Male Urogenital Diseases

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Germ Cells Tumors

Ovarian Germ Cell Tumor

Testicular Germ Cell Tumor

Embryonal Carcinoma

Extragonadal Germ Cell Tumor

Central Nervous System Germinoma

Ovarian Cancer

Testicular Yolk Sac Tumor

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Bleomycin

Etoposide

Cisplatin

Etoposide phosphate

Enzyme Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

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.

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

conventional surgery

cisplatin

etoposide

bleomycin sulfate

laboratory biomarker analysis

Anne Frazier, MD

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.

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.

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

A Phase III Study Of Reduced Therapy In The Treatment Of Children With Low And Intermediate Risk Extracranial Germ Cell Tumors

Proportion of patients event free at 3 years following enrollment. Event-free survival is not a primary outcome measure for Arm 2 patients.

Percentage probability of being alive at 3 years following enrollment.

Calculated to quantify the treatment cost associated with this regimen.

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

National Cancer Institute (NCI)

Children's Oncology Group

Only patients who are considered eligible contribute to the tabulation of adverse events. For Arm/Group Title "No Intervention" (Arm/Group Description: "Arm 2") 104 eligible patients contribute as described from the Participant Flow as 112 enrolled minus 8 ineligible. For Arm/Group Title "Experimental" (Arm/Group Description: "Arm 1") 182 eligible patients contribute as described from the Participant Flow as 190 enrolled minus 8 ineligible.

Arm 2 (Observation)

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 (2nd-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.

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Arm I (Chemotherapy)

Arm I

Arm 2

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

New Zealand

Canada

United States

Australia

Switzerland

Guam

Region of Enrollment

Only patients considered eligible contribute to the tabulation of AEs. Arm 1: 182 eligible as described in Participant Flow as 190 enrolled, -8 ineligible. Arm 2: 104 eligible as described in Participant Flow as 112 enrolled, -8 ineligible.

Results Reporting Coordinator

Arm 1

181 patients were evaluated for event free survival through 3 years for patients enrolled on Arm 1. Event-free survival is not a primary outcome measure for Arm 2 patients.

Event-Free Survival (EFS)

Overall Survival (OS)

182 patients were enrolled on intermediate risk chemotherapy and were evaluable for this secondary endpoint

Days Hospitalized for Patients Who Receive Chemotherapy

Abdominal pain

Acute kidney injury

Lymphocyte count decrease

Iincrease in alanine aminotransferase

Neutrophil count decrease

Anemia

Increase in aspartate aminotransferase

Catheter related infection

Constipation

Dehydration

Encephalopathy

Febrile neutropenia

Fever

Hyperglycemia

Hyperkalemia

Hypocalcemia

Hypokalemia

Hypomagnesemia

Hyponatremia

Hypophosphatemia

Small intestine obstruction

Nausea

Non-cardiac chest pain

Other gastrointestinal disorders

Other infection

Platelet count decrease

Syncope

Vomiting

White blood cell decrease

Wound infection

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

Overall Study

Spots Global Cancer Trial Database for childhood embryonal tumor