Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Completed 18 and over NCI CALGB-90106 CALGB-90106, NCT00072215

Special Category: CTSU trial

Objectives

Primary

1. 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

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

Entry 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]

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

Patient Characteristics:

Age

• 18 and over

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• 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

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Robert Motzer, MD, Protocol chair		Ph: 646-422-4312; 800-525-2225

Registry Information
Official Title		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
Trial Start Date		2004-04-15
Trial Completion Date		2008-04-01
Registered in ClinicalTrials.gov		NCT00072215
Date Submitted to PDQ		2003-09-24
Information Last Verified		2004-11-30
NCI Grant/Contract Number		CA31946