Ensayos clínicos

Inclusion Criteria

• Patients ≥ 18 years of age
• Patients with newly diagnosed GCT
• Pathology confirmation of GCT histology 
• In exceptional circumstances, patients without pathological diagnosis may be included by the national principal investigator (or national Co-PI or MSKCC Co-PI if the national PI is unavailable) if they meet the one of the following criteria
  • a testicular mass (detected clinically and/or by ultrasound)
  • mediastinal or retroperitoneal lymphadenopathy
  • 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.
• 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) 
    • 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
      • 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)
      • Serum human chorionic gonadotrophin (HCG) from 5,000 to < 50,000 MIU/mL
      • Serum alpha-fetoprotein (AFP) from 1,000 to <10,000 ng/mL 
    • 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)
    • Testis or retroperitoneal NSGCT primary with non-pulmonary visceral metastasis (liver, bone, brain, etc) regardless the STM values.
    • Mediastinal NSGCT primary site of disease regardless the presence/absence of visceral metastasis or STM values.
    • Testis or retroperitoneal NSGCT primary without non-pulmonary visceral metastasis but with poor-risk STM values
      • LDH ≥ 10 x ULN
      • HCG ≥ 50,000 MIU/mL
      • 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.
• Diffusion lung capacity for carbon monoxide (DLCO) adjusted for hemoglobin ≥ 60% predicted, except if related to high volume metastatic GCT to the lungs in which case there is no minimum DLCO requirement
  • In some cases, patients may not be able to undergo PFT testing due to the severity of their presentation. such as those with high volume lung metastases or tumor-related pain (from large mediastinal masses, pleural disease, etc.) limiting their ability to complete PFTs
  • Even when PFTs can be completed in these cases, patients will still be eligible if the low DLCO can be attributed directly to the patient's disease (e.g., large mediastinal mass) rather than intrinsic lung disease. 
    • Most patients in this situation will be expected to receive disease-stabilizing chemotherapy.
  • An unadjusted DLCO may be used in place of the DLCO adjusted for hemoglobin in certain situations as per institutional policy.
    • For example, MSKCC policy is to not adjust the DLCO for hemoglobin when the hemoglobin is ≥ 14.6 g/dL for males and ≥ 13.4 g/dL for females. In these cases, the unadjusted DLCO must be >60% predicted.
• 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 
  • Estimated GFR (by Cockcroft-Gault) ≥ 50mL/min 
  • 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 the national  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 metastatic disease to the liver, AST/ALT may be ≤ 5x ULN and total bilirubin ≤ 2.5 x ULN.
  • If known or suspected to have Gilbert's disease, total bilirubin up to ≤ 2.5 x ULN is allowed.

Exclusion Criteria

• Any prior chemotherapy.
  • Only exception will be patients with a history of stage I seminoma treated with adjuvant carboplatin for 1 or 2 cycles.
• Concurrent treatment with any cytotoxic therapy.
• Known concurrent malignancy
  • except for non-melanoma skin cancer
• Patients known to be HIV positive and receiving HAART
• Presence of an active infection
  • Patients with fever assessed to be "tumor fever" but without active evidence of infection (e.g. blood cultures are negative) are eligible. 
  • Patients who have an infection but without evidence of fever for 48 hours on antibiotics will be eligible.
• Inability to comply with the treatment protocol or to undergo prespecified follow-up tests for safety or effectiveness.
• Pregnant patients are ineligible