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

Not Recruiting

Trial ID: NCT01873326


The purpose of this study is to learn about the safety and effectiveness of two different drug combinations in patients who have intermediate- and poor-risk germ cell tumors (GCT). One combination of drugs, paclitaxel, ifosfamide and cisplatin (TIP), is experimental. The other combination of drugs, bleomycin, etoposide and cisplatin (BEP), is the standard of care treatment for intermediate- and poor-risk germ cell tumors. However, BEP does not cure every patient and therefore newer treatments are needed.

Official Title

Randomized Phase II Trial of Paclitaxel, Ifosfamide and Cisplatin (TIP) Versus Bleomycin, Etoposide and Cisplatin (BEP) for Patients With Previously Untreated Intermediate- and Poor-Risk Germ Cell Tumors

Stanford Investigator(s)

Sandy Srinivas
Sandy Srinivas

Professor of Medicine (Oncology) and, by courtesy, of Urology


Inclusion Criteria:

   - 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

      - 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

      - 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. Since there is
      no minimum DLCO for these patients, under these extraordinary circumstances, this
      will be allowed. 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

   - 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.

Exclusion Criteria:

   - Any prior chemotherapy. The 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.
   In addition, 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


drug: Paclitaxel

drug: Ifosfamide

drug: Cisplatin

drug: Mesna

drug: Bleomycin

drug: Etoposide

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305

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