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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

Phase 2
18 Years
Open (Enrolling)
Germ Cell Tumors

Thank you

Trial Information

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

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 primary investigator at
MSKCC (or Dr. Hu or Dr. Motzer if the 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 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

- Patients must have recovered from prior surgery based on treating physician's

- 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 rare cases, such patients who may not be
able to undergo PFT testing due to the severity of their presentation. Since there is
no minimum DLCO for these patients, under these extraordinary circumstances, this
will be allowed. Patients in this situation will be expected to receive
disease-stabilizing chemotherapy.

- Laboratory criteria for protocol entry (obtained ≤ 14 days before initiation of

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

- Serum creatinine ≤ upper limit of normal (ULN) or creatinine clearance ≥ 50
mL/min, unless renal insufficiency is due to tumoral ureteral obstruction in
which case eligibility will be determined by the primary investigator with
notification of the 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.

Patients must be classified as having intermediate or poor-risk NSGCT, as follows:

o Intermediate-risk (Modified*)

a) Testis or retroperitoneal primary 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

- 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 primary with non-pulmonary visceral metastasis
(liver, bone, brain, etc) regardless the STM values.

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

3. Testis or retroperitoneal 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

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.

- Hypoxia or DLCO <60% related to an underlying lung disease and not related to GCT

- Inability to comply with the treatment protocol or to undergo prespecified follow-up
tests for safety or effectiveness.

- Pregnant patients are ineligible

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

favorable best response rate

Outcome Description:

Favorable best response is defined as complete response or partial response with negative tumor markers. Patients will be considered evaluable for the primary endpoint of favorable response within the first 6 months if they complete at least 3 cycles of study treatment (without switch to an alternative chemotherapy regimen) and achieve a confirmed partial response with negative markers or confirmed complete response (considered as favorable responses). Patients will also be considered evaluable for the primary endpoint if they develop disease progression during the treatment portion of the study regardless of how many cycles of chemotherapy they received or if they achieve an incomplete response after completion of study treatment (considered as not having a favorable response)."

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Darren Feldman, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

June 2013

Completion Date:

June 2018

Related Keywords:

  • Germ Cell Tumors
  • newly diagnosed GCT
  • Intermediate
  • Poor-Risk
  • 13-074
  • Neoplasms, Germ Cell and Embryonal



Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
Memorial Sloan-Kettering Cancer Center at Mercy Medical CenterRockville Centre, New York  11570
Memoral Sloan Kettering Cancer CenterBasking Ridge, New Jersey  
Memorial Sloan-Kettering Cancer Center @ SuffolkCommack, New York  11725
Memoral Sloan Kettering Cancer Center@Phelps Memorial HospitalSleepy Hollow, New York