Combination Chemotherapy in Treating Young Patients With Recurrent or Resistant Malignant Germ Cell Tumors

Children's Oncology Group

Status and phase

Completed

Phase 2

Conditions

Childhood Extragonadal Malignant Germ Cell Tumor

Testicular Choriocarcinoma

Testicular Embryonal Carcinoma

Recurrent Ovarian Germ Cell Tumor

Ovarian Choriocarcinoma

Recurrent Malignant Testicular Germ Cell Tumor

Ovarian Embryonal Carcinoma

Ovarian Yolk Sac Tumor

Testicular Mixed Choriocarcinoma and Yolk Sac Tumor

Testicular Yolk Sac Tumor

Childhood Malignant Ovarian Germ Cell Tumor

Recurrent Childhood Malignant Germ Cell Tumor

Testicular Mixed Choriocarcinoma and Embryonal Carcinoma

Childhood Extracranial Germ Cell Tumor

Testicular Mixed Embryonal Carcinoma and Yolk Sac Tumor

Childhood Malignant Testicular Germ Cell Tumor

Treatments

Drug: Carboplatin

Other: Laboratory Biomarker Analysis

Drug: Paclitaxel

Drug: Ifosfamide

Biological: Filgrastim

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT00467051

CDR0000542424

AGCT0521 (Other Identifier)

COG-AGCT0521

U10CA098543 (U.S. NIH Grant/Contract)

NCI-2009-00374 (Registry Identifier)

Details and patient eligibility

About

This phase II trial is studying how well giving combination chemotherapy works in treating young patients with recurrent or resistant malignant germ cell tumors. Drugs used in chemotherapy, such as paclitaxel, ifosfamide, and carboplatin, 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.

Full description

PRIMARY OBJECTIVES:

I. Determine the response rate in pediatric patients with recurrent or resistant malignant germ cell tumors (GCT) treated with paclitaxel, ifosfamide, and carboplatin.

SECONDARY OBJECTIVES:

I. Determine the toxicity of this regimen in these patients. II. To Collect tissue for the tumor bank that will aid in the identification of the biological characteristics of recurrent GCT.

OUTLINE: This is a multicenter study.

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1 and ifosfamide IV over 1 hour on days 1-5. Beginning on day 6, patients receive filgrastim (G-CSF) subcutaneously or IV once daily until blood count returns to normal. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 5 years.

Enrollment

20 patients

Sex

All

Ages

Under 21 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

Histologically confirmed (at original diagnosis) extracranial germ cell tumor (GCT) containing 1 of the following malignant elements:
- Yolk sac tumor (endodermal sinus tumor)
- Choriocarcinoma
- Embryonal carcinoma
Meets 1 of the following disease criteria:
- Recurrent malignant disease
- Chemotherapy-resistant disease
- Relapsed disease
- Disease refractory to conventional therapy
Measurable disease
Must have received a prior first-line chemotherapy regimen that included cisplatin
Patients with tumor marker (AFP and/or BHCG) elevation alone or bone scan findings alone are not eligible*
Patients with immature teratoma (any grade), germinoma, sex-cord stromal tumors, or recurrent GCT previously treated with surgery alone are not eligible
Karnofsky performance status (PS) 50-100% (age > 16 years) OR Lansky PS 50-100% (age ≤ 16 years) OR ECOG PS 0-2
Life expectancy ≥ 8 weeks
Absolute neutrophil count ≥ 750/mm³
Platelet count ≥ 75,000/mm³ (transfusion independent)
Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR creatinine normal based on age/gender, as defined by the following:
- ≤ 0.4 mg/dL (1 month to < 6 months of age)
- ≤ 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)
- ≤ 1.4 mg/dL (13 to ≥ 16 years of age) (female)
- ≤ 1.5 mg/dL (13 to < 16 years of age) (male)
- ≤ 1.7 mg/dL (≥ 16 years of age) (male)
Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
ALT < 2.5 times ULN for age
Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by gated radionuclide study
No dyspnea at rest
No exercise intolerance
Pulse oximetry > 94% (if there is clinical indication for determination)
Patients with seizure disorder are eligible provided they are on non-enzyme inducing anticonvulsants and seizures are well controlled
No CNS toxicity > grade 2
No active graft-versus-host disease
No allergy to Cremophor EL or castor oil
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No other concurrent chemotherapy or immunomodulating agents
Recovered from prior chemotherapy, immunotherapy, or radiotherapy
At least 1 week since prior growth factors (2 weeks for pegfilgrastim)
At least 1 week since prior biologic therapy
At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosourea)
At least 2 weeks since prior local palliative radiotherapy (i.e., small port)
At least 6 months since prior craniospinal radiotherapy or radiotherapy to ≥ 50% of pelvis
At least 6 weeks since other prior substantial bone marrow radiotherapy
At least 6 months since prior allogeneic stem cell transplantation
Concurrent radiotherapy to localized painful lesions allowed provided at least 1 measurable lesion is not irradiated