Combination Chemotherapy in Treating Young Patients With Recurrent or Resistant Malignant Germ Cell Tumors - Full Text View

Purpose

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.

Condition	Intervention	Phase
Childhood Extracranial Germ Cell Tumor Childhood Extragonadal Germ Cell Tumor Childhood Malignant Ovarian Germ Cell Tumor Childhood Malignant Testicular Germ Cell Tumor Ovarian Choriocarcinoma Ovarian Embryonal Carcinoma Ovarian Yolk Sac Tumor Recurrent Childhood Malignant Germ Cell Tumor Recurrent Malignant Testicular Germ Cell Tumor Recurrent Ovarian Germ Cell Tumor Testicular Choriocarcinoma Testicular Choriocarcinoma and Embryonal Carcinoma Testicular Choriocarcinoma and Yolk Sac Tumor Testicular Embryonal Carcinoma Testicular Embryonal Carcinoma and Yolk Sac Tumor Testicular Yolk Sac Tumor	Drug: paclitaxel Drug: carboplatin Drug: ifosfamide Biological: filgrastim Other: laboratory biomarker analysis	Phase 2


Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment
Official Title:	Treatment of Recurrent or Resistant Pediatric Malignant Germ Cell Tumors With Paclitaxel, Ifosfamide and Carboplatin

Resource links provided by NLM:

Drug Information available for: Ifosfamide

Genetic and Rare Diseases Information Center resources: Testicular Cancer Malignant Germ Cell Tumor Embryonal Carcinoma Choriocarcinoma Testicular Yolk Sac Tumor Ovarian Germ Cell Tumor Extragonadal Germ Cell Tumor Ovarian Cancer

U.S. FDA Resources

Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:

Response Rate as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria [ Time Frame: 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:

Toxicity as Measured by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events ( CTCAE) Version 4.0 [ Time Frame: During and after completion of study treatment ]
All patients who experience any grade 2 or higher toxicity at any time during the two treatment cycles or who receive at least all required Ifosfamide therapy after enrollment will be considered evaluable for toxicity. The descriptions and grading scales found in the revised NCI CTCAE version 4 will be used.


Enrollment:	20
Study Start Date:	November 2007
Study Completion Date:	March 2012
Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Treatment (chemotherapy, biological therapy) 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.	Drug: paclitaxel Given IV dosage 135 mg/m2/dose Other Names: Anzatax Asotax TAX Taxol Drug: carboplatin Given IV dosage in mg/m2 = Target AUC (mg•min/mL) x [(0.93 x GFR mL/min/m2) + 15]= 6.5 x [(0.93 x GFR mL/min/m2) + 15]. (BSA = body surface area in square meters). GFR is reported in institutions as "uncorrected" or "raw" (not normalized to BSA) or "corrected." This number needs to be converted to GFR in mL/min/m2. Other Names: Carboplat CBDCA JM-8 Paraplat Paraplatin Drug: ifosfamide Given IV dosage 1800 mg/m2/dose Other Names: Cyfos Holoxan IFF IFX IPP Biological: filgrastim Given IV or subcutaneously dosage 1,080mg/m2/day divided to three equal doses of 360mg/m2 Other Names: G-CSF Neupogen Other: laboratory biomarker analysis Optional correlative studies

Arms

Assigned Interventions

Experimental: Treatment (chemotherapy, biological therapy)

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.

Drug: paclitaxel

Given IV dosage 135 mg/m2/dose

Other Names:

Anzatax
Asotax
TAX
Taxol

Drug: carboplatin

Given IV dosage in mg/m2 = Target AUC (mg•min/mL) x [(0.93 x GFR mL/min/m2) + 15]= 6.5 x [(0.93 x GFR mL/min/m2) + 15]. (BSA = body surface area in square meters). GFR is reported in institutions as "uncorrected" or "raw" (not normalized to BSA) or "corrected." This number needs to be converted to GFR in mL/min/m2.

Other Names:

Carboplat
CBDCA
JM-8
Paraplat
Paraplatin

Drug: ifosfamide

Given IV dosage 1800 mg/m2/dose

Other Names:

Cyfos
Holoxan
IFF
IFX
IPP

Biological: filgrastim

Given IV or subcutaneously dosage 1,080mg/m2/day divided to three equal doses of 360mg/m2

Other Names:

G-CSF
Neupogen

Other: laboratory biomarker analysis

Optional correlative studies

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.

Eligibility

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Ages Eligible for Study:	up to 21 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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 Central Nervous System (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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00467051

Show 35 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Carlos Rodriguez-Galindo, MD	Children's Oncology Group

More Information


Responsible Party:	Children's Oncology Group
ClinicalTrials.gov Identifier:	NCT00467051 History of Changes
Other Study ID Numbers:	AGCT0521 NCI-2009-00374 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) COG-AGCT0521 ( Other Identifier: Children's Oncology Group ) CDR0000542424 ( Other Identifier: Clinical Trials.gov ) U10CA098543 ( U.S. NIH Grant/Contract )
First Submitted:	April 25, 2007
First Posted:	April 27, 2007
Results First Submitted:	March 11, 2015
Results First Posted:	March 20, 2015
Last Update Posted:	March 15, 2017
Last Verified:	February 2017

Additional relevant MeSH terms:


Carcinoma Neoplasms Neoplasms, Germ Cell and Embryonal Germinoma Ovarian Neoplasms Testicular Neoplasms Carcinoma, Embryonal Endodermal Sinus Tumor Choriocarcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Endocrine Gland Neoplasms Neoplasms by Site Ovarian Diseases Adnexal Diseases	Genital Diseases, Female Genital Neoplasms, Female Urogenital Neoplasms Endocrine System Diseases Gonadal Disorders Genital Neoplasms, Male Genital Diseases, Male Testicular Diseases Mesonephroma Trophoblastic Neoplasms Adenocarcinoma Pregnancy Complications, Neoplastic Pregnancy Complications Paclitaxel Isophosphamide mustard