Paclitaxel, Ifosfamide and Cisplatin (TIP) Versus Bleomycin, Etoposide and Cisplatin (BEP) for Patients With Previously Untreated Intermediate- and Poor-risk Germ Cell Tumors

Patients ≥ 18 years of age.

Patients with newly diagnosed GCT

Pathology confirmation of GCT histology at MSKCC or a collaborating treating institution. In exceptional circumstances, patients without pathological diagnosis may be included in the study following discussion with the national principal investigator, Dr. Feldman,(or national Co-PI or MSKCC Co-PI if the national PI is unavailable) if they meet the one of the following criteria:

Patients with a testicular mass (detected clinically and/or by ultrasound), and/or mediastinal or retroperitoneal lymphadenopathy or pineal tumor AND elevated serum tumor markers (HCG and/or AFP). Patients with elevated LDH only will not be included without pathological confirmation of GCT since LDH is a nonspecific marker for GCT and could potentially be elevated in other malignancies such as lymphomas.

This is because patients may present with a clinical scenario consistent with GCT (elevated serum tumor markers, testicular mass and retroperitoneal lymphadenopathy) with a concurrent life-threatening oncologic emergency that require immediate treatment. In this case, initial treatment without biopsy confirmation is usually recommended and tissue confirmation may be obtained after initiating therapy.

Patients must have measurable or evaluable disease.

Patients must be classified as having intermediate or poor-risk germ cell tumor, as follows:

* Intermediate-risk (Modified\*) a) Testis or retroperitoneal primary NSGCT with lymph node and/or lung metastasis but without non-pulmonary visceral metastasis AND any of the following pretreatment serum tumor marker (STM) values: i. Lactate dehydrogenase (LDH) from 3 to \<10 x ULN (\*This differs from the original IGCCCG criteria which includes patients with LDH from 1.5 to 10 x ULN).

ii. Serum human chorionic gonadotrophin (HCG) from 5,000 to \< 50,000 MIU/mL iii. Serum alpha-fetoprotein (AFP) from 1,000 to \<10,000 ng/mL b) Seminoma histology regardless the primary site or serum tumor markers with any non-pulmonary visceral metastasis (liver, bone, brain, etc).

Poor-risk (any of the following):

1. Testis or retroperitoneal NSGCT primary with non-pulmonary visceral metastasis (liver, bone, brain, etc) regardless the STM values.

2. Mediastinal NSGCT primary site of disease regardless the presence/absence of visceral metastasis or STM values.

3. Testis or retroperitoneal NSGCT primary without non-pulmonary visceral metastasis but with poor-risk STM values:

i. LDH ≥ 10 x ULN

ii. HCG ≥ 50,000 MIU/mL

iii. AFP ≥ 10,000 ng/mL

* Patients who received prior radiation therapy (RT) for treatment of germ cell tumor are eligible for this study as long as there is evidence of progressive disease determined by tumor markers or other sites of metastases outside of the radiated site. Radiation must be completed prior to starting chemotherapy with the exception of brain metastases where chemotherapy and radiation can be given concurrently. Toxicity from radiation must have recovered to grade 1 or less prior to initiating chemotherapy.

* Patients must have recovered from prior surgery based on treating physician's discretion.

* Patients of reproductive potential must agree to use effective contraception during the period of therapy

* Signed informed consent.

Laboratory criteria for protocol entry (obtained ≤ 14 days before initiation of therapy):

WBC ≥ 3000/UL and Platelet count ≥ 100,000/UL

Serum creatinine ≤ 1.5 mg/dL or estimated GFR (by Cockcroft-Gault) ≥50mL/min or 12 or 24 hour urine creatinine clearance ≥ 50 mL/min, unless renal insufficiency is due to tumoral ureteral obstruction in which case eligibility will be determined by national the principal investigator (or national co-PI or MSKCC co-PI if the national PI is unavailable) with notification of the MSKCC IRB.

AST/ALT ≤ 3 x ULN and total bilirubin ≤ 2.0 x ULN. In the setting of metastatic disease to the liver, AST/ALT may be ≤5x ULN and total bilirubin ≤2.5 x ULN. If a patient is known or suspected to have Gilbert's disease, total bilirubin up to ≤2.5 x ULN is allowed.

What this study is about