Cisplatin and Ifosfamide Combined With Either Paclitaxel or Vinblastine in Treating Men With Progressive or Recurrent Metastatic Germ Cell Tumors

A Randomized Phase III Study of Paclitaxel, Ifosfamide and Cisplatin Versus Vinblastine, Ifosfamide and Cisplatin as Second-Line Therapy for Patients With Relapsed/Resistant Germ Cell Tumors

RATIONALE: Drugs used in chemotherapy, such as ifosfamide, cisplatin, paclitaxel, and vinblastine, work in different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether ifosfamide and cisplatin are more effective when combined with paclitaxel or vinblastine in treating germ cell tumors.

PURPOSE: This randomized phase III trial is studying paclitaxel, ifosfamide, and cisplatin to see how well they work compared to vinblastine, ifosfamide, and cisplatin in treating men with progressive or recurrent metastatic germ cell tumors.

Study Overview

• Status: Terminated
• Conditions: Testicular Germ Cell Tumor; Extragonadal Germ Cell Tumor
• Intervention / Treatment: Drug: paclitaxel; Drug: cisplatin; Drug: ifosfamide; Drug: vinblastine

Detailed Description

OBJECTIVES:

Primary

• Compare the overall survival of men with progressive or recurrent metastatic germ cell tumors treated with paclitaxel, ifosfamide, and cisplatin vs vinblastine, ifosfamide, and cisplatin as second-line therapy.

Secondary

• Compare the progression-free survival of patients treated with these regimens.
• Compare the toxicity profiles of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior complete response or partial response with negative markers for at least 6 months (yes vs no) and relapse at least 2 years after completing first-line chemotherapy for germ cell tumors (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive paclitaxel IV over 24 hours on day 1 and cisplatin IV over 20-30 minutes and ifosfamide IV over 30 minutes on days 2-5. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 7-18 OR pegfilgrastim SC once within 24-72 hours after completion of chemotherapy.
• Arm II: Patients receive vinblastine IV on days 1 and 2 and cisplatin IV over 20-30 minutes and ifosfamide IV over 30 minutes on days 1-5. Patients also receive G-CSF SC on days 7-18 OR pegfilgrastim as in arm I.

In both arms, treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 2 years, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill Cancer Centre at McGill University
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Northeast Alabama Regional Medical Center
  • California
    • La Jolla, California, United States, 92093-0658
      • Rebecca and John Moores UCSD Cancer Center
    • Los Angeles, California, United States, 90048
      • Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
    • San Diego, California, United States, 92161
      • Veterans Affairs Medical Center - San Diego
    • San Diego, California, United States, 92134-3202
      • Naval Medical Center - San Diego
    • San Francisco, California, United States, 94115
      • UCSF Comprehensive Cancer Center
    • San Francisco, California, United States, 94121
      • Veterans Affairs Medical Center - San Francisco
  • Delaware
    • Newark, Delaware, United States, 19713
      • CCOP - Christiana Care Health Services
  • District of Columbia
    • Washington, District of Columbia, United States, 20422
      • Veterans Affairs Medical Center - Washington, DC
    • Washington, District of Columbia, United States, 20007
      • Lombardi Cancer Center at Georgetown University Medical Center
    • Washington, District of Columbia, United States, 20307-5001
      • Walter Reed Army Medical Center
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Broward General Medical Center
    • Hollywood, Florida, United States, 33021
      • Memorial Cancer Institute at Memorial Regional Hospital
    • Miami Beach, Florida, United States, 33140
      • CCOP - Mount Sinai Medical Center
    • Orlando, Florida, United States, 32804
      • Florida Hospital Cancer Institute
    • West Palm Beach, Florida, United States, 33401
      • Palm Beach Cancer Institute - West Palm Beach
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Veterans Affairs Medical Center - Chicago (Westside Hospital)
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago Cancer Research Center
    • Chicago, Illinois, United States, 60640
      • Louis A. Weiss Memorial Hospital
    • Chicago, Illinois, United States, 60612
      • MBCCOP - University of Illinois at Chicago
    • Evanston, Illinois, United States, 60201
      • CCOP - Evanston
    • Peoria, Illinois, United States, 61615-7828
      • CCOP - Illinois Oncology Research Association
    • River Forest, Illinois, United States, 60305
      • West Suburban Center for Cancer Care
  • Indiana
    • Fort Wayne, Indiana, United States, 46885-5099
      • Fort Wayne Medical Oncology and Hematology, Incorporated
    • South Bend, Indiana, United States, 46601
      • CCOP - Northern Indiana CR Consortium
  • Iowa
    • Iowa City, Iowa, United States, 52242-1009
      • Holden Comprehensive Cancer Center at University of Iowa
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Baptist Hospital East - Louisville
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Greenebaum Cancer Center at University of Maryland Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
    • Worcester, Massachusetts, United States, 01655
      • UMASS Memorial Cancer Center - University Campus
  • Michigan
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417
      • Veterans Affairs Medical Center - Minneapolis
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Cancer Center
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Veterans Affairs Medical Center - Columbia (Truman Memorial)
    • Columbia, Missouri, United States, 65203
      • Ellis Fischel Cancer Center at University of Missouri - Columbia
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Cancer Center
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198-7680
      • UNMC Eppley Cancer Center at the University of Nebraska Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • CCOP - Southern Nevada Cancer Research Foundation
    • Las Vegas, Nevada, United States, 89106
      • Veterans Affairs Medical Center - Las Vegas
  • New Hampshire
    • Hooksett, New Hampshire, United States, 03106
      • New Hampshire Oncology-Hematology, PA - Hooksett
    • Lebanon, New Hampshire, United States, 03756-0002
      • Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cancer Institute of New Jersey at the Cooper University Hospital
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • Buffalo, New York, United States, 14215
      • Veterans Affairs Medical Center - Buffalo
    • East Syracuse, New York, United States, 13057
      • CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
    • Jamaica, New York, United States, 11432
      • Queens Cancer Center of Queens Hospital
    • Manhasset, New York, United States, 11030
      • CCOP - North Shore University Hospital
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10021
      • New York Weill Cornell Cancer Center at Cornell University
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
    • Syracuse, New York, United States, 13210
      • Veterans Affairs Medical Center - Syracuse
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University Hospital
  • North Carolina
    • Asheville, North Carolina, United States, 28805-9913
      • Veterans Affairs Medical Center - Asheville
    • Chapel Hill, North Carolina, United States, 27599-7295
      • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
    • Concord, North Carolina, United States, 28025
      • NorthEast Oncology Associates - Concord
    • Durham, North Carolina, United States, 27705
      • Veterans Affairs Medical Center - Durham
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center
    • Fayetteville, North Carolina, United States, 28302-2000
      • Cape Fear Valley Medical Center
    • Goldsboro, North Carolina, United States, 27534-9479
      • CCOP - Southeast Cancer Control Consortium
    • Pinehurst, North Carolina, United States, 28374
      • Comprehensive Cancer Center at Moore Regional Hospital
    • Wilmington, North Carolina, United States, 28402-9025
      • Zimmer Cancer Center at New Hanover Regional Medical Center
    • Winston-Salem, North Carolina, United States, 27157-1082
      • Comprehensive Cancer Center at Wake Forest University
  • Ohio
    • Columbus, Ohio, United States, 43210-1240
      • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Miriam Hospital at Lifespan
  • Texas
    • Dallas, Texas, United States, 75219
      • Veterans Affairs Medical Center - Dallas
    • Dallas, Texas, United States, 75390-8852
      • Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
  • Vermont
    • Burlington, Vermont, United States, 05401-3498
      • Vermont Cancer Center at University of Vermont
  • Virginia
    • Charlottesville, Virginia, United States, 22902
      • Martha Jefferson Hospital
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates - Norfolk
    • Richmond, Virginia, United States, 23298-0037
      • MBCCOP - Massey Cancer Center
    • Roanoke, Virginia, United States, 24014
      • Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke
  • West Virginia
    • Huntington, West Virginia, United States, 25701
      • St. Mary's Medical Center
  • Wisconsin
    • Rhinelander, Wisconsin, United States, 54501
      • Ministry Medical Group at Saint Mary's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed germ cell tumor (GCT), including 1 of the following primary tumor sites:

  • Seminoma

    • Testis
    • Retroperitoneum
    • Mediastinum
    • Other extragonadal site

  • Nonseminoma

    • Testis
    • Retroperitoneum

    • Other extragonadal site

      • No tumor of the mediastinum

• Must have evidence of metastatic disease, including either of the following:

  • Unidimensionally measurable lesions

    • At least 20 mm by conventional techniques (e.g., physical exam for clinically palpable lymph nodes and superficial skin lesions or chest x-ray for clearly defined lung lesions surrounded by aerated lung) OR at least 10 mm by spiral CT scan or MRI

  • Nonmeasurable lesions, including the following:

    • Small lesions
    • Bone lesions
    • Pleural or pericardial effusions
    • Ascites
    • Irradiated lesions, unless progression is documented after radiotherapy

• Progressive or recurrent disease meeting at least 1 of the following criteria:

  • Measurable progressive disease
  • Biopsy-proven residual disease
  • Persistently elevated or rising ß-human chorionic gonadotropin (HCG) or alpha-fetoprotein (AFP) titers with no other clear cause for elevation

• Previously treated with 1 and only 1 regimen comprising etoposide and cisplatin with or without bleomycin AND exhibits clinical resistance by at least 1 of the following conditions after therapy*:

  • Progressive GCT after a partial response to first-line therapy
  • Relapse after complete response (CR) to first-line therapy, including partial response (PR) surgically converted to CR
  • Second testicular primary with evidence of metastases after first-line therapy
  • Relapse after adjuvant chemotherapy NOTE: *Patients failing to achieve PR or CR with first-line therapy as evidenced by rising markers or new disease within 4 weeks of first-line therapy are not eligible

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL (transfusion allowed)

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal* (ULN)
• AST and ALT ≤ 2.5 times ULN* NOTE: *Unless hepatic metastases are present

Renal

• Creatinine ≤ 1.5 times ULN OR
• Creatinine clearance ≥ 50 mL/min

Other

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior dose-intensive therapy with stem cell replacement

Chemotherapy

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy
• No prior paclitaxel
• No prior docetaxel
• No prior ifosfamide
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy
• Concurrent or sequential radiotherapy to brain metastases allowed
• No other concurrent palliative radiotherapy

Surgery

• See Disease Characteristics
• Concurrent surgery for brain metastases allowed

Other

• Recovered from prior therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Regimen A: TIP	Drug: paclitaxel; given IV; Drug: cisplatin; given IV; Drug: ifosfamide; given IV
EXPERIMENTAL: Regimen B: VeIP	Drug: cisplatin; given IV; Drug: ifosfamide; given IV; Drug: vinblastine; given IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival	2 months

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (ACTUAL): April 1, 2005
• Study Completion (ACTUAL): April 1, 2005

Study Registration Dates

• First Submitted: November 4, 2003
• First Submitted That Met QC Criteria: November 5, 2003
• First Posted (ESTIMATE): November 6, 2003

Study Record Updates

• Last Update Posted (ESTIMATE): July 4, 2016
• Last Update Submitted That Met QC Criteria: July 1, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: stage III malignant testicular germ cell tumor; recurrent malignant testicular germ cell tumor; testicular embryonal carcinoma; testicular choriocarcinoma; testicular yolk sac tumor; testicular embryonal carcinoma and teratoma; testicular embryonal carcinoma and teratoma with seminoma; testicular embryonal carcinoma and yolk sac tumor; testicular embryonal carcinoma and yolk sac tumor with seminoma; testicular embryonal carcinoma and seminoma; testicular yolk sac tumor and teratoma; testicular yolk sac tumor and teratoma with seminoma; testicular choriocarcinoma and yolk sac tumor; testicular choriocarcinoma and embryonal carcinoma; testicular choriocarcinoma and teratoma; testicular choriocarcinoma and seminoma; recurrent extragonadal non-seminomatous germ cell tumor; recurrent extragonadal seminoma; stage IV extragonadal non-seminomatous germ cell tumor; stage IV extragonadal seminoma; recurrent extragonadal germ cell tumor; testicular immature teratoma; testicular mature teratoma; testicular seminoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Urogenital Neoplasms; Neoplasms by Site; Endocrine System Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Genital Neoplasms, Male; Testicular Diseases; Neoplasms; Neoplasms, Germ Cell and Embryonal; Testicular Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Paclitaxel; Cisplatin; Ifosfamide; Vinblastine
• Other Study ID Numbers: CALGB-90106; U10CA031946 (U.S. NIH Grant/Contract); CDR0000339340 (REGISTRY: NCI Physician Data Query)