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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborators:
University of Southern California-James Hu, MD (national Co-PI)
Mayo Clinic
University of Pittsburgh
University of North Carolina
University of Chicago
Stanford University
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01873326
First received: June 5, 2013
Last updated: June 30, 2014
Last verified: June 2014

June 5, 2013
June 30, 2014
June 2013
June 2018   (final data collection date for primary outcome measure)
favorable best response rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
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)."
favorable best response rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
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 best response if they develop progression of disease at any time point after initiation of chemotherapy (these patients will be categorized as incomplete responders and therefore as having not achieved a favorable response).
Complete list of historical versions of study NCT01873326 on ClinicalTrials.gov Archive Site
  • overall best response [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Overall best response refers to the best response achieved by a patient to either TIP or BEP over the course of the entire study.
  • progression-free survival (PFS) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Progression-free survival (PFS) will be calculated from the date of treatment start until disease progression, death, or last followup, whichever comes first. The following are included as PFS events: incomplete response (IR), relapse or disease progression, and death.
  • overall survival (OS) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Overall survival will be calculated from the date of treatment start until death, regardless of the cause.
  • toxicity [ Time Frame: 30 days after completion of the last cycle of chemotherapy. ] [ Designated as safety issue: Yes ]
    Toxicity will be assessed based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The maximum grade of each toxicity will be recorded for each patient over the course of treatment (all cycles). Special emphasis will be placed on comparisons of the frequency of Grade 3/4 toxicities between the TIP and BEP arms.
  • overall best response [ Time Frame: after 4 cycles of chemotherapy ] [ Designated as safety issue: No ]
    Overall best response refers to the best response achieved by a patient to either TIP or BEP over the course of the entire study.
  • progression-free survival (PFS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Progression-free survival (PFS) will be calculated from the date of treatment start until disease progression, death, or last followup, whichever comes first. The following are included as PFS events: incomplete response (IR), relapse or disease progression, and death.
  • overall survival (OS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Overall survival will be calculated from the date of treatment start until death, regardless of the cause.
  • toxicity [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Toxicity will be assessed based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The maximum grade of each toxicity will be recorded for each patient over the course of treatment (all cycles). Special emphasis will be placed on comparisons of the frequency of Grade 3/4 toxicities between the TIP and BEP arms.
Not Provided
Not Provided
 
Paclitaxel, Ifosfamide and Cisplatin (TIP) Versus Bleomycin, Etoposide and Cisplatin (BEP) for Patients With Previously Untreated Intermediate- and Poor-risk Germ Cell Tumors
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

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Germ Cell Tumors
  • Drug: Paclitaxel
  • Drug: Ifosfamide
  • Drug: Cisplatin
  • Drug: Mesna
  • Drug: Bleomycin
  • Drug: Etoposide
  • Experimental: Paclitaxel, Ifosfamide and Cisplatin (TIP)

    Paclitaxel 120 mg/m2 IV over 120-180 min Days 1 and 2 Mesna 120 mg/m2 IV (duration of infusion per institutional guidelines) approximately 30 minutes prior to initiation of ifosfamide Days 1-5 Ifosfamide 1200 mg/m2 IV over approximately 60 to 120 min Days 1-5 or per institutional guidelines (mixed 1:1 with mesna) Mesna* 1200 mg/m2 IV over approximately 60-120 min or per institutional guidelines (mixed 1:1 with ifosfamide) Cisplatin 20 mg/m2 IV over approximately 30 min Days 1-5

    *Additional mesna may be given at the discretion of the investigator

    Interventions:
    • Drug: Paclitaxel
    • Drug: Ifosfamide
    • Drug: Cisplatin
    • Drug: Mesna
  • Active Comparator: Bleomycin, Etoposide and Cisplatin (BEP)
    Cisplatin 20 mg/m2 IV over approximately 30 min Days 1-5 Etoposide 100 mg/m2 IV over approximately 1 hour Days 1-5 Bleomycin 30 U flat dose IV push Days 2, 8 and 15 (all +/- 4 days)
    Interventions:
    • Drug: Cisplatin
    • Drug: Bleomycin
    • Drug: Etoposide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
88
June 2018
June 2018   (final data collection date for primary outcome measure)

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 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 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 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..

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.
  • Inability to comply with the treatment protocol or to undergo prespecified follow-up tests for safety or effectiveness.
  • Pregnant patients are ineligible
Both
18 Years and older
No
Contact: Darren Feldman, MD 646-422-4491
Contact: Robert Motzer, MD 646-422-4312
United States
 
NCT01873326
13-074
Not Provided
Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
  • University of Southern California-James Hu, MD (national Co-PI)
  • Mayo Clinic
  • University of Pittsburgh
  • University of North Carolina
  • University of Chicago
  • Stanford University
Principal Investigator: Darren Feldman, MD Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP