Combination Chemotherapy and Pegfilgrastim in Treating Patients With Previously Untreated Germ Cell Tumors

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy, such as cisplatin, ifosfamide, and paclitaxel, 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. Colony-stimulating factors, such as pegfilgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. PURPOSE: This phase II trial is studying the side effects and how well giving combination chemotherapy together with pegfilgrastim works in treating patients with previously untreated germ cell tumors.

Detailed Description
-----------------
OBJECTIVES: Determine the efficacy of chemotherapy comprising paclitaxel, ifosfamide, and cisplatin in combination with pegfilgrastim in patients with previously untreated intermediate- or poor-risk germ cell tumors. Determine the safety of this regimen in these patients. Determine the toxicity of this regimen in these patients. OUTLINE: Patients receive paclitaxel IV over 120-180 minutes on days 1 and 2, cisplatin IV over 30 minutes and ifosfamide IV over 120 minutes on days 1-5, and pegfilgrastim subcutaneously on day 6. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Some patients may required surgery after chemotherapy and, if viable non-teratomatous germ cell tumor is found in the surgical specimen and there is no interval disease progression, these patients may receive 1-2 more courses of chemotherapy after surgery. After completion of study treatment, patients are followed up at 28 days and then every 2 months for up to 1 year. PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study.

Official Title
-----------------
Phase II Trial of Paclitaxel, Ifosfamide, and Cisplatin in Previously Untreated Intermediate and Poor Risk Germ Cell Tumor Patients

Conditions
-----------------
Brain and Central Nervous System Tumors, Extragonadal Germ Cell Tumor, Ovarian Cancer, Teratoma, Testicular Germ Cell Tumor

Intervention / Treatment
-----------------
* Biological: pegfilgrastim
* Drug: cisplatin
* Drug: ifosfamide
* Drug: paclitaxel


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed germ cell tumor meeting 1 of the following criteria: Poor risk, defined by any of the following: Testis or retroperitoneal primary site nonseminoma histology without visceral metastases but with poor-risk markers, defined by any of the following: Pretreatment serum lactate dehydrogenase (LDH) > 10 times upper limit of normal (ULN) Pretreatment serum human chorionic gonadotropin (HCG) > 50,000 IU/L Pretreatment serum alpha fetoprotein (AFP) > 10,000 ng/mL Testis or retroperitoneal primary site nonseminoma histology with one or more nonpulmonary visceral metastases, including any of the following (regardless of serum tumor marker values): Bone metastases Brain metastases Hepatic metastases Any nonpulmonary metastases (i.e., skin, spleen) Mediastinal primary site nonseminoma histology regardless of serum tumor marker levels or presence/absence of visceral metastases Modified intermediate risk, defined by any of the following: Testis or retroperitoneal primary site nonseminoma histology with no nonpulmonary visceral metastases, and with any of the following serum marker values: Pretreatment serum LDH 3.0-10 times ULN Pretreatment serum HCG 5,000-50,000 IU/L Pretreatment serum AFP 1,000-10,000 ng/mL Seminoma histology with one or more nonpulmonary visceral metastases, including any of the following (regardless of serum tumor marker values or primary site): Bone metastases Brain metastases Hepatic metastases Any nonpulmonary visceral metastases (i.e., skin, spleen) Previously untreated disease Measurable or evaluable disease PATIENT CHARACTERISTICS: WBC ≥ 3,000/mm^3 Platelet count ≥ 100,000/mm^3 Creatinine normal or creatinine clearance > 50 mL/min (unless renal dysfunction is due to tumor obstructing the ureters) AST and ALT ≤ 3 times ULN Bilirubin ≤ 2.0 times ULN Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No concurrent malignancy except for nonmelanoma skin cancer No known HIV positivity No active infections PRIOR CONCURRENT THERAPY: Recovered from prior surgery More than 30 days since prior radiotherapy and recovered (unless evidence of progressive disease has been documented) No prior chemotherapy No other concurrent cytotoxic therapy Concurrent radiotherapy and surgery allowed for treatment of brain metastases

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paclitaxel, Ifosfamide, and Cisplatin<br>-Paclitaxel is administered first, 120 mg/m2 on days 1 and 2 every three weeks for four cycles. Cisplatin is administered at 20 mg/m2 over approximately 30 minutes daily for five days every three weeks for four courses. -The ifosfamide is given last with 1200 mg/m2 daily for five days every three weeks for four cycles. | Biological: pegfilgrastim<br> <br> Drug: cisplatin<br> <br> Drug: ifosfamide<br> <br> Drug: paclitaxel<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Complete Response | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions | Up to 8 years | 
| Percentage of Participants With Progression Free Survival | Progression Free Survival at 3 years. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions | 3 years | 
| Number of Patients With Treatment Related Toxicity | Toxicity evaluated and graded according to the National Cancer Institute, Version 3.0 | 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage II malignant testicular germ cell tumor, stage III malignant testicular germ cell tumor, testicular choriocarcinoma and embryonal carcinoma, testicular choriocarcinoma and seminoma, testicular choriocarcinoma and teratoma, testicular choriocarcinoma and yolk sac tumor, testicular choriocarcinoma, testicular embryonal carcinoma and seminoma, testicular embryonal carcinoma and teratoma with seminoma, testicular embryonal carcinoma and teratoma, testicular embryonal carcinoma and yolk sac tumor with seminoma, testicular embryonal carcinoma and yolk sac tumor, testicular embryonal carcinoma, testicular seminoma, testicular yolk sac tumor and teratoma with seminoma, testicular yolk sac tumor and teratoma, testicular yolk sac tumor, stage I malignant testicular germ cell tumor, adult central nervous system germ cell tumor, ovarian choriocarcinoma, ovarian dysgerminoma, ovarian embryonal carcinoma, ovarian yolk sac tumor, ovarian immature teratoma, ovarian mature teratoma, ovarian monodermal and highly specialized teratoma, ovarian polyembryoma, ovarian mixed germ cell tumor, stage IV ovarian germ cell tumor, stage IV extragonadal seminoma, stage I extragonadal non-seminomatous germ cell tumor, stage II extragonadal non-seminomatous germ cell tumor, stage III extragonadal non-seminomatous germ cell tumor, stage IV extragonadal non-seminomatous germ cell tumor, adult teratoma, testicular immature teratoma, testicular mature teratoma, stage IA ovarian germ cell tumor, stage IB ovarian germ cell tumor, stage IC ovarian germ cell tumor, stage IIA ovarian germ cell tumor, stage IIB ovarian germ cell tumor, stage IIC ovarian germ cell tumor, stage IIIA ovarian germ cell tumor, stage IIIB ovarian germ cell tumor, stage IIIC ovarian germ cell tumor