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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


Phase 3
18 Years
N/A
Not Enrolling
Male
Extragonadal Germ Cell Tumor, Testicular Germ Cell Tumor

Thank you

Trial Information

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


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.

PROJECTED ACCRUAL: A total of 470 patients (235 per treatment arm) will be accrued for this
study within 5.5 years.

Inclusion Criteria


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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Overall survival

Outcome Time Frame:

2 months

Safety Issue:

No

Principal Investigator

Robert J. Motzer, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000339340

NCT ID:

NCT00072215

Start Date:

April 2004

Completion Date:

Related Keywords:

  • Extragonadal Germ Cell Tumor
  • Testicular Germ Cell Tumor
  • recurrent malignant testicular germ cell tumor
  • stage III malignant testicular germ cell tumor
  • testicular choriocarcinoma and embryonal carcinoma
  • testicular choriocarcinoma and seminoma
  • testicular choriocarcinoma and teratoma
  • testicular choriocarcinoma and yolk sac tumor
  • testicular choriocarcinoma
  • testicular embryonal carcinoma and seminoma
  • testicular embryonal carcinoma and teratoma with seminoma
  • testicular embryonal carcinoma and teratoma
  • testicular embryonal carcinoma and yolk sac tumor with seminoma
  • testicular embryonal carcinoma and yolk sac tumor
  • testicular embryonal carcinoma
  • testicular seminoma
  • testicular yolk sac tumor and teratoma with seminoma
  • testicular yolk sac tumor and teratoma
  • testicular yolk sac tumor
  • recurrent extragonadal non-seminomatous germ cell tumor
  • recurrent extragonadal seminoma
  • stage IV extragonadal non-seminomatous germ cell tumor
  • stage IV extragonadal seminoma
  • testicular immature teratoma
  • testicular mature teratoma
  • recurrent extragonadal germ cell tumor
  • Neoplasms, Germ Cell and Embryonal

Name

Location

Roswell Park Cancer Institute Buffalo, New York  14263
Memorial Sloan-Kettering Cancer Center New York, New York  10021
Walter Reed Army Medical Center Washington, District of Columbia  20307-5000
University of Chicago Cancer Research Center Chicago, Illinois  60637
University of Minnesota Cancer Center Minneapolis, Minnesota  55455
Duke Comprehensive Cancer Center Durham, North Carolina  27710
CCOP - Kansas City Kansas City, Missouri  64131
CCOP - Southern Nevada Cancer Research Foundation Las Vegas, Nevada  89106
CCOP - Christiana Care Health Services Wilmington, Delaware  19899
CCOP - Mount Sinai Medical Center Miami Beach, Florida  33140
CCOP - North Shore University Hospital Manhasset, New York  11030
CCOP - Southeast Cancer Control Consortium Winston-Salem, North Carolina  27104-4241
MBCCOP - Massey Cancer Center Richmond, Virginia  23298-0037
CCOP - Illinois Oncology Research Association Peoria, Illinois  61602
Comprehensive Cancer Center at Wake Forest University Winston-Salem, North Carolina  27157-1082
Martha Jefferson Hospital Charlottesville, Virginia  22901
MBCCOP - University of Illinois at Chicago Chicago, Illinois  60612
CCOP - Evanston Evanston, Illinois  60201
CCOP - Northern Indiana CR Consortium South Bend, Indiana  46601
Holden Comprehensive Cancer Center at University of Iowa Iowa City, Iowa  52242-1002
UMASS Memorial Cancer Center - University Campus Worcester, Massachusetts  01605-2982
Ellis Fischel Cancer Center at University of Missouri - Columbia Columbia, Missouri  65203
Siteman Cancer Center at Barnes-Jewish Hospital Saint Louis, Missouri  63110
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center Lebanon, New Hampshire  03756-0002
Cancer Institute of New Jersey at the Cooper University Hospital Camden, New Jersey  08103-1489
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill Chapel Hill, North Carolina  27599-7570
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Columbus, Ohio  43210-1240
North Shore University Hospital Manhasset, New York  11030
Veterans Affairs Medical Center - Chicago (Westside Hospital) Chicago, Illinois  60612
Naval Medical Center - San Diego San Diego, California  92134-3202
Veterans Affairs Medical Center - San Francisco San Francisco, California  94121
Baptist Hospital East - Louisville Louisville, Kentucky  40207
CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C. Syracuse, New York  13217
Veterans Affairs Medical Center - Minneapolis Minneapolis, Minnesota  55417
Veterans Affairs Medical Center - Columbia (Truman Memorial) Columbia, Missouri  65201
Veterans Affairs Medical Center - Buffalo Buffalo, New York  14215
Veterans Affairs Medical Center - Syracuse Syracuse, New York  13210
Veterans Affairs Medical Center - Durham Durham, North Carolina  27705
Rebecca and John Moores UCSD Cancer Center La Jolla, California  92093-0658
Broward General Medical Center Fort Lauderdale, Florida  33316
Florida Hospital Cancer Institute Orlando, Florida  32804
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute Boston, Massachusetts  02115
Northeast Alabama Regional Medical Center Anniston, Alabama  36207
Veterans Affairs Medical Center - San Diego San Diego, California  92161
UCSF Comprehensive Cancer Center San Francisco, California  94115
Veterans Affairs Medical Center - Washington, DC Washington, District of Columbia  20422
Louis A. Weiss Memorial Hospital Chicago, Illinois  60640
West Suburban Center for Cancer Care River Forest, Illinois  60305
Fort Wayne Medical Oncology and Hematology, Incorporated Fort Wayne, Indiana  46885-5099
Veterans Affairs Medical Center - Las Vegas Las Vegas, Nevada  89106
Queens Cancer Center of Queens Hospital Jamaica, New York  11432
Veterans Affairs Medical Center - Asheville Asheville, North Carolina  28805
Veterans Affairs Medical Center - Dallas Dallas, Texas  75216
Virginia Oncology Associates - Norfolk Norfolk, Virginia  23502
St. Mary's Medical Center Huntington, West Virginia  25701
Oklahoma University Medical Center Oklahoma City, Oklahoma  73104
Mount Sinai Medical Center New York, New York  10029
SUNY Upstate Medical University Hospital Syracuse, New York  13210
Vermont Cancer Center at University of Vermont Burlington, Vermont  05405-0075
Lombardi Cancer Center at Georgetown University Medical Center Washington, District of Columbia  20007
Greenebaum Cancer Center at University of Maryland Medical Center Baltimore, Maryland  21201
UNMC Eppley Cancer Center at the University of Nebraska Medical Center Omaha, Nebraska  68198-7680
New Hampshire Oncology-Hematology, PA - Hooksett Hooksett, New Hampshire  03106
NorthEast Oncology Associates - Concord Concord, North Carolina  28025
Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke Roanoke, Virginia  24014
Memorial Cancer Institute at Memorial Regional Hospital Hollywood, Florida  33021
Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph Saint Joseph, Michigan  49085
New York Weill Cornell Cancer Center at Cornell University New York, New York  10021
Cape Fear Valley Medical Center Fayetteville, North Carolina  28302-2000
Comprehensive Cancer Center at Moore Regional Hospital Pinehurst, North Carolina  28374
Zimmer Cancer Center at New Hanover Regional Medical Center Wilmington, North Carolina  28402-9025
Miriam Hospital at Lifespan Providence, Rhode Island  02906
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center Los Angeles, California  90048-1865
Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas Dallas, Texas  75390-9063
Missouri Baptist Cancer Center St. Louis, Missouri  63131
Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital Pittsburgh, Pennsylvania  15224-1791
Ministry Medical Group at Saint Mary's Hospital Rhinelander, Wisconsin  54501
Palm Beach Cancer Institute - West Palm Beach West Palm Beach, Florida  33401