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

NCT01873326 | Active Not Recruiting Phase 2

• 1 other identifier: 13-074
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 13

Brief Summary

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.

Conditions

Germ Cell Tumors

Keywords

newly diagnosed GCT; Intermediate; Poor-Risk; BLEOMYCIN; CISPLATIN; ETOPOSIDE (VP-16); IFOSFAMIDE; TAXOL (PACLITAXEL); 13-074

Outcome Measures

Primary Outcomes (1)

• favorable best response rate

  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)."

  6 months

Secondary Outcomes (4)

• overall best response

  3 years

• progression-free survival (PFS)

  3 years

• overall survival (OS)

  3 years

• toxicity

  30 days after completion of the last cycle of chemotherapy.

Study Arms (2)

Paclitaxel, Ifosfamide and Cisplatin (TIP)

EXPERIMENTAL

Paclitaxel 120 mg/m2 IV over 120-180 min Days 1 and 2 (+/- 4 days)\* Mesna 120 mg/m2 IV (duration of infusion per institutional guidelines) approximately 30 minutes prior to initiation of ifosfamide Days 1-5 (+/- 4 days)\* Ifosfamide 1200 mg/m2 IV over approximately 60 to 120 min Days 1-5 or per institutional guidelines (mixed 1:1 with mesna) (+/- 4 days)\* Mesna\*\* 1200 mg/m2 IV over approximately 60-120 min or per institutional guidelines (mixed 1:1 with ifosfamide)(+/- 4 days)\* Cisplatin 20 mg/m2 IV over approximately 30 min Days 1-5 (+/- 4 days)\* \*\*Additional mesna may be given at the discretion of the investigator \*Paclitaxel or Ifosfamide or Mesna or Cisplatin or any combination of these agents can be held as needed for patient safety on a given day between days 1-5 but must be made up within 4 days to avoid a protocol violation.

Drug: Paclitaxel; Drug: Ifosfamide; Drug: Cisplatin; Drug: Mesna

Bleomycin, Etoposide and Cisplatin (BEP)

ACTIVE COMPARATOR

Cisplatin 20 mg/m2 IV over approximately 30 min Days 1-5 (+/- 4 days)\* Etoposide 100 mg/m2 IV over approximately 1 hour Days 1-5 (+/- 4 days)\* Bleomycin 30 U flat dose IV push Days 2, 8 and 15 (all +/- 4 days) \*Etoposide or Cisplatin or both can be held as needed for patient safety on a given day between days 1-5 but must be made up within 4 days to avoid a protocol violation.

Drug: Cisplatin; Drug: Bleomycin; Drug: Etoposide

Interventions

Paclitaxel DRUG

Paclitaxel, Ifosfamide and Cisplatin (TIP)

Ifosfamide DRUG

Paclitaxel, Ifosfamide and Cisplatin (TIP)

Cisplatin DRUG

Bleomycin, Etoposide and Cisplatin (BEP); Paclitaxel, Ifosfamide and Cisplatin (TIP)

Mesna DRUG

Paclitaxel, Ifosfamide and Cisplatin (TIP)

Bleomycin DRUG

Bleomycin, Etoposide and Cisplatin (BEP)

Etoposide DRUG

Bleomycin, Etoposide and Cisplatin (BEP)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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):
• 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:
• i. LDH ≥ 10 x ULN
• ii. HCG ≥ 50,000 MIU/mL

You may not qualify if:

• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• University of Southern California: collaborator
• Mayo Clinic: collaborator
• University of Pittsburgh: collaborator
• University of North Carolina: collaborator
• University of Chicago: collaborator
• Stanford University: collaborator
• University of Texas Southwestern Medical Center: collaborator

Study Sites (13)

University of Southern California

Los Angeles, California, 90033, United States

Location

Stanford University Medical Center

Stanford, California, 94305-5408, United States

Location

University of Chicago

Chicago, Illinois, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Memorial Sloan Kettering Cancer Center

Basking Ridge, New Jersey, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Follow-up Only)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27514, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Neoplasms, Germ Cell and Embryonal

Interventions

Paclitaxel; Ifosfamide; Cisplatin; Mesna; Bleomycin; Etoposide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glucosides; Glycosides

Study Officials

• Darren Feldman, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2013
• First Posted: June 10, 2013
• Study Start: June 1, 2013
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: July 3, 2025

Record last verified: 2025-07

Locations

US (13)