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

• ClinicalTrials.gov Identifier: NCT00072215
• Recruitment Status: Terminated
• First Posted: November 6, 2003
• Last Update Posted: July 4, 2016
• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Alliance for Clinical Trials in Oncology

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Extragonadal Germ Cell Tumor; Testicular Germ Cell Tumor	Drug: cisplatin; Drug: ifosfamide; Drug: paclitaxel; Drug: vinblastine	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Study Start Date: April 2004
• Actual Primary Completion Date: April 2005
• Actual Study Completion Date: April 2005

Arms and Interventions

Arm	Intervention/treatment
Experimental: Regimen A: TIP	Drug: cisplatin; given IV; Drug: ifosfamide; given IV; Drug: paclitaxel; given IV
Experimental: Regimen B: VeIP	Drug: cisplatin; given IV; Drug: ifosfamide; given IV; Drug: vinblastine; given IV

Outcome Measures

Primary Outcome Measures :

1. Overall survival [ Time Frame: 2 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 120 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

  Show 79 Study Locations

Sponsors and Collaborators

Alliance for Clinical Trials in Oncology

National Cancer Institute (NCI)

Investigators

• Study Chair: Robert J. Motzer, MD; Memorial Sloan Kettering Cancer Center

More Information

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00072215 History of Changes
• Other Study ID Numbers: CALGB-90106; U10CA031946 ( U.S. NIH Grant/Contract ); CDR0000339340 ( Registry Identifier: NCI Physician Data Query )
• First Posted: November 6, 2003
• Last Update Posted: July 4, 2016
• Last Verified: July 2016

Keywords provided by Alliance for Clinical Trials in Oncology:

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

Additional relevant MeSH terms:

Neoplasms, Germ Cell and Embryonal; Testicular Neoplasms; Neoplasms; Neoplasms by Histologic Type; Endocrine Gland Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Endocrine System Diseases; Testicular Diseases; Gonadal Disorders; Paclitaxel; Vinblastine; Albumin-Bound Paclitaxel; Cisplatin; Ifosfamide; Isophosphamide mustard; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Alkylating; Alkylating Agents