Surgery and Combination Chemotherapy in Treating Children With Extracranial Germ Cell Tumors - Full Text View

Sponsor:	Children's Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00053352

Purpose

RATIONALE: 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.

PURPOSE: 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.

Condition	Intervention	Phase
Pediatric Germ Cell Tumor Extragonadal Germ Cell Tumor Ovarian Cancer	Biological: bleomycin sulfate Drug: cisplatin Drug: etoposide Procedure: conventional surgery	Phase III

Study Type:	Interventional
Study Design:	Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase III Study Of Reduced Therapy In The Treatment Of Children With Low And Intermediate Risk Extracranial Germ Cell Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer Ovarian Cancer

Drug Information available for: Bleomycin Cisplatin Etoposide Etoposide phosphate Bleomycin sulfate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Event-free survival [ Designated as safety issue: No ]

Estimated Enrollment:	306
Study Start Date:	November 2003
Estimated Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

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).
Determine the percentage of patients with stage I ovarian or stage I testicular GCTs for whom chemotherapy can be eliminated.
Determine the percentage of intermediate-risk patients who require only 3 courses of therapy.
Determine the acute toxic effects of compressed therapy in these patients.
Determine the long-term sequelae in patients treated with this regimen.
Determine the number of hospital days and total drug doses required for patients treated with compressed therapy.
Compare the number of protocol-directed treatment days used in CCG-8882 vs the number of treatment days used in this study.
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 therapy: 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.

PROJECTED ACCRUAL: A total of 306 patients (126 with low-risk disease and 180 with intermediate-risk disease) will be accrued for this study within 6 years.

Eligibility

Ages Eligible for Study:	up to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Extracranial germ cell tumor that contains 1 of the following malignant histologies:
- Yolk sac tumor
- Embryonal carcinoma
- Choriocarcinoma
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.
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

PATIENT CHARACTERISTICS:

Age

21 and under at diagnosis (under 15 for patients with primary testicular tumors; if over 15, will be treated as adults)

Performance status

Not specified

Life expectancy

Not specified

Hematopoietic

Not specified

Hepatic

Not specified

Renal

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)

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

No prior chemotherapy

Endocrine therapy

Not specified

Radiotherapy

No prior radiotherapy

Surgery

See Disease Characteristics

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00053352

Show 175 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

A. Lindsay Frazier, MD, ScM

Dana-Farber Cancer Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Gregory H. Reaman, Children's Oncology Group - Group Chair Office
ClinicalTrials.gov Identifier:	NCT00053352 History of Changes
Other Study ID Numbers:	CDR0000269433, COG-AGCT0132
Study First Received:	January 27, 2003
Last Updated:	April 2, 2011
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

childhood malignant ovarian germ cell tumor
childhood extragonadal germ cell tumor
childhood malignant testicular germ cell tumor
childhood extracranial germ cell tumor
childhood teratoma

Additional relevant MeSH terms:

Ovarian Neoplasms
Neoplasms, Germ Cell and Embryonal
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders

Neoplasms by Histologic Type
Bleomycin
Cisplatin
Etoposide
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on February 09, 2012