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

Phase 2

Completed

Conditions: Childhood Extracranial Germ Cell Tumor
Childhood Malignant Ovarian Germ Cell Tumor
Childhood Malignant Testicular Germ Cell Tumor
Ovarian Yolk Sac Tumor
Recurrent Childhood Malignant Germ Cell Tumor
Testicular Mixed Choriocarcinoma and Yolk Sac Tumor
Ovarian Embryonal Carcinoma
Recurrent Malignant Testicular Germ Cell Tumor
Ovarian Choriocarcinoma
Recurrent Ovarian Germ Cell Tumor

Interventions: Drug: Carboplatin
Biological: Filgrastim
Drug: Ifosfamide
Other: Laboratory Biomarker Analysis
Drug: Paclitaxel

Registration Number: NCT00467051

Lead Sponsor: Children's Oncology Group

Brief Summary: 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.

Detailed 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (chemotherapy, biological therapy)	Filgrastim	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.
Treatment (chemotherapy, biological therapy)	Laboratory Biomarker Analysis	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.
Treatment (chemotherapy, biological therapy)	Carboplatin	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.
Treatment (chemotherapy, biological therapy)	Ifosfamide	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.
Treatment (chemotherapy, biological therapy)	Paclitaxel	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.

Primary Outcome Measures

Name	Time	Method
Response Rate as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria	At baseline (day 1) and after completion of protocol therapy (2 cycles or 42 days)	Patients who demonstrate a PR or CR, as defined below, will be considered as responders. RECIST criteria: CR (complete response) = disappearance of all target lesions, PR (partial response) = 30% decrease in the sum of the longest diameter of target lesions, PD (progressive disease) = 20% increase in the sum of the longest diameter of target lesions and SD (stable disease) = small changes that do not meet above criteria.

Secondary Outcome Measures

Name	Time	Method
The Number of Patients Who Experience at Least One Grade 3 or Higher CTC Version 4 Toxicity.	Two cycles of chemotherapy; expected to be 42 days of treatment.

Trial Locations

Locations (95): The University of Arizona Medical Center-University Campus
🇺🇸
Tucson, Arizona, United States
University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
Kaiser Permanente Downey Medical Center
🇺🇸
Downey, California, United States
Miller Children's and Women's Hospital Long Beach
🇺🇸
Long Beach, California, United States
Children's Hospital Los Angeles
🇺🇸
Los Angeles, California, United States
Cedars Sinai Medical Center
🇺🇸
Los Angeles, California, United States
Lucile Packard Children's Hospital Stanford University
🇺🇸
Palo Alto, California, United States
UCSF Medical Center-Mount Zion
🇺🇸
San Francisco, California, United States
UCSF Medical Center-Parnassus
🇺🇸
San Francisco, California, United States
Harbor-University of California at Los Angeles Medical Center
🇺🇸
Torrance, California, United States
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The University of Arizona Medical Center-University Campus
🇺🇸Tucson, Arizona, United States