Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Recurrence

Teratoma

Testicular Neoplasms

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Germ Cells Tumors

Ovarian Germ Cell Tumor

Testicular Germ Cell Tumor

Malignant Germ Cell Tumor

Extragonadal Germ Cell Tumor

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Carboplatin

Bleomycin

Etoposide

Cisplatin

Ifosfamide

Etoposide phosphate

Vinblastine

Isophosphamide mustard

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Tubulin Modulators

Antimitotic Agents

bleomycin sulfate

carboplatin

cisplatin

etoposide

ifosfamide

vinblastine sulfate

adjuvant therapy

conventional surgery

Juliet Hale, MD

RATIONALE: Sometimes, after surgery, the tumor may not need additional treatment until it progresses. In this case, observation may be sufficient. Drugs used in chemotherapy 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. Giving combination chemotherapy after surgery may kill any remaining tumor cells.

PURPOSE: This phase III trial is studying how well observation and/or combination chemotherapy works after surgery or biopsy in treating young patients with extracranial germ cell tumors.

OBJECTIVES:

* Stratify and reduce treatment for pediatric patients with extracranial germ cell tumors while maintaining event-free survival.
* Treat newly diagnosed patients with extracranial germ cell tumors requiring chemotherapy with a carboplatin-based strategy.
* Develop a common strategy for the treatment of patients with recurrent or progressive extracranial germ cell tumors.
* Register all cases of mature and immature teratoma.
* Develop a common strategy for the management of immature and mature teratoma, including follow-up strategies to permit early detection of yolk sac recurrence.

OUTLINE: This is a multicenter study.

Patients who have not had prior biopsy or surgical resection undergo biopsy (if feasible) or surgical resection. Patients with mature or immature teratoma undergo observation. These patients who relapse (i.e., tumor regrowth) may undergo further surgical resection unless tumor markers are significantly elevated. If the tumor markers are significantly elevated, these patients proceed to JEB chemotherapy according to risk group. Patients with all other malignant germ cell tumors are assigned to 1 of 3 treatment groups according to risk.

* Low-risk group: Patients with normal tumor markers undergo observation. Patients with rising tumor markers only AND no imageable tumor proceed to treatment as in the intermediate-risk group. Patients with rising tumor markers AND/OR imageable tumor are considered to have relapsed and proceed to treatment as in the intermediate- or high-risk group.
* Intermediate-risk group: Patients receive JEB chemotherapy comprising etoposide IV over 4 hours on days 1-3, carboplatin IV over 1 hour on day 2, and bleomycin IV over 30 minutes on day 3. Treatment repeats every 21 days for 4 courses. Patients with residual tumors after completion of chemotherapy may undergo second-look surgery.
* High-risk group: Patients receive JEB chemotherapy as in the intermediate-risk group for 6 courses. Patients with residual tumors after completion of chemotherapy may undergo second-look surgery.
* Relapse therapy: Patients in the intermediate- or high-risk group who relapse after completion of JEB chemotherapy receive vinblastine IV on days 1 and 2, ifosfamide IV over 1 hour on days 1-5, and cisplatin IV on days 1-5. Treatment repeats every 21 days for 6 courses.

PROJECTED ACCRUAL: A total of 105 patients will be accrued for this study.

Observation and/or Combination Chemotherapy After Surgery or Biopsy in Treating Young Patients With Extracranial Germ Cell Tumors

Protocol for the Treatment of Extracranial Germ Cell Tumours in Children and Adolescents (GC III)

Children's Cancer and Leukaemia Group

Carcinoma

Endodermal Sinus Tumor

Carcinoma, Embryonal

Choriocarcinoma

Germinoma

Neoplasms, Glandular and Epithelial

Disease Attributes

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Genital Neoplasms, Male

Genital Diseases, Male

Male Urogenital Diseases

Testicular Diseases

Trophoblastic Neoplasms

Adenocarcinoma

Pregnancy Complications, Neoplastic

Embryonal Carcinoma

Testicular Yolk Sac Tumor

Central Nervous System Germinoma

Antirheumatic Agents

Paclitaxel

Albumin-Bound Paclitaxel

Cyclophosphamide

Lenograstim

Mechlorethamine

Adjuvants, Immunologic

Immunologic Factors

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.

Filgrastim

Laboratory Biomarker Analysis

Carlos Rodriguez-Galindo

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.

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.

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

Treatment of Recurrent or Resistant Pediatric Malignant Germ Cell Tumors With Paclitaxel, Ifosfamide and Carboplatin

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.

National Cancer Institute (NCI)

Children's Oncology Group

SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.

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.

paclitaxel: Given IV dosage 135 mg/m2/dose

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.

ifosfamide: Given IV dosage 1800 mg/m2/dose

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

laboratory biomarker analysis: Optional correlative studies

Treatment (Chemotherapy, Biological Therapy)

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Canada

Australia

Puerto Rico

Region of Enrollment

Results Reporting Coordinator

Responder

Non-Responder

Response Rate as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria

Experimental

The Number of Patients Who Experience at Least One Grade 3 or Higher CTC Version 4 Toxicity.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Observation and/or Combination Chemotherapy After Surgery or Biopsy in Treating Young Patients With Extracranial Germ Cell Tumors	NCT00274950	Childhood Germ ... Extragonadal Ge... Ovarian Cancer	bleomycin sulfa... carboplatin cisplatin etoposide ifosfamide vinblastine sul... adjuvant therap... conventional su...	- 17 Years	National Cancer Institute (NCI)
Combination Chemotherapy in Treating Young Patients With Recurrent or Resistant Malignant Germ Cell Tumors	NCT00467051	Childhood Extra... Childhood Extra... Childhood Malig... Childhood Malig... Ovarian Chorioc... Ovarian Embryon... Ovarian Yolk Sa... Recurrent Child... Recurrent Malig... Recurrent Ovari... Testicular Chor... Testicular Embr... Testicular Mixe... Testicular Mixe... Testicular Mixe... Testicular Yolk...	Carboplatin Filgrastim Ifosfamide Laboratory Biom... Paclitaxel	- 21 Years	Children's Oncology Group
Cyproheptadine in Preventing Weight Loss in Children Receiving Chemotherapy for Cancer	NCT01132547	Cancer	cyproheptadine ... placebo	2 Years - 21 Years	University of South Florida
Sodium Thiosulfate in Preventing Hearing Loss in Young Patients Receiving Cisplatin for Newly Diagnosed Germ Cell Tumor, Hepatoblastoma, Medulloblastoma, Neuroblastoma, Osteosarcoma, or Other Malignancy	NCT00716976	Brain Tumor Central Nervous... Childhood Germ ... Extragonadal Ge... Liver Cancer Neuroblastoma Ototoxicity Ovarian Cancer Sarcoma	sodium thiosulf... examination	1 Year - 18 Years	Children's Oncology Group
Observation and/or Combination Chemotherapy After Surgery or Biopsy in Treating Young Patients With Extracranial Germ Cell Tumors	NCT00274950	Childhood Germ ... Extragonadal Ge... Ovarian Cancer	bleomycin sulfa... carboplatin cisplatin etoposide ifosfamide vinblastine sul... adjuvant therap... conventional su...	- 17 Years	National Cancer Institute (NCI)
Surgery and Combination Chemotherapy in Treating Children With Extracranial Germ Cell Tumors	NCT00053352	Childhood Embry... Childhood Extra... Childhood Extra... Childhood Malig... Childhood Malig... Childhood Terat... Ovarian Embryon... Ovarian Yolk Sa... Stage II Malign... Stage IIA Ovari... Stage IIB Ovari... Stage IIC Ovari... Stage III Malig... Stage IIIA Ovar... Stage IIIB Ovar... Stage IIIC Ovar... Testicular Chor... Testicular Embr...	conventional su... cisplatin etoposide bleomycin sulfa... laboratory biom...	- 21 Years	Children's Oncology Group

Spots Global Cancer Trial Database for childhood extracranial germ cell tumor