Combination Chemotherapy and Pegfilgrastim in Treating Patients With Previously Untreated Germ Cell Tumors

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Completed; Phase 2

Conditions: Teratoma; Brain and Central Nervous System Tumors; Extragonadal Germ Cell Tumor; Ovarian Cancer; Testicular Germ Cell Tumor

Treatments: Drug: cisplatin; Drug: ifosfamide; Drug: paclitaxel; Biological: pegfilgrastim

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00470366

MSKCC-07044

07-044

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as cisplatin, ifosfamide, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Colony-stimulating factors, such as pegfilgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy.

PURPOSE: This phase II trial is studying the side effects and how well giving combination chemotherapy together with pegfilgrastim works in treating patients with previously untreated germ cell tumors.

Full description

OBJECTIVES:

• Determine the efficacy of chemotherapy comprising paclitaxel, ifosfamide, and cisplatin in combination with pegfilgrastim in patients with previously untreated intermediate- or poor-risk germ cell tumors.
• Determine the safety of this regimen in these patients.
• Determine the toxicity of this regimen in these patients.

OUTLINE: Patients receive paclitaxel IV over 120-180 minutes on days 1 and 2, cisplatin IV over 30 minutes and ifosfamide IV over 120 minutes on days 1-5, and pegfilgrastim subcutaneously on day 6. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Some patients may required surgery after chemotherapy and, if viable non-teratomatous germ cell tumor is found in the surgical specimen and there is no interval disease progression, these patients may receive 1-2 more courses of chemotherapy after surgery.

After completion of study treatment, patients are followed up at 28 days and then every 2 months for up to 1 year.

PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study.

Enrollment: 60 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed germ cell tumor meeting 1 of the following criteria:

  • Poor risk, defined by any of the following:

    • Testis or retroperitoneal primary site nonseminoma histology without visceral metastases but with "poor-risk" markers, defined by any of the following:

      • Pretreatment serum lactate dehydrogenase (LDH) > 10 times upper limit of normal (ULN)
      • Pretreatment serum human chorionic gonadotropin (HCG) > 50,000 IU/L
      • Pretreatment serum alpha fetoprotein (AFP) > 10,000 ng/mL

    • Testis or retroperitoneal primary site nonseminoma histology with one or more nonpulmonary visceral metastases, including any of the following (regardless of serum tumor marker values):

      • Bone metastases
      • Brain metastases
      • Hepatic metastases
      • Any nonpulmonary metastases (i.e., skin, spleen)

    • Mediastinal primary site nonseminoma histology regardless of serum tumor marker levels or presence/absence of visceral metastases

  • Modified intermediate risk, defined by any of the following:

    • Testis or retroperitoneal primary site nonseminoma histology with no nonpulmonary visceral metastases, and with any of the following serum marker values:

      • Pretreatment serum LDH 3.0-10 times ULN
      • Pretreatment serum HCG 5,000-50,000 IU/L
      • Pretreatment serum AFP 1,000-10,000 ng/mL

    • Seminoma histology with one or more nonpulmonary visceral metastases, including any of the following (regardless of serum tumor marker values or primary site):

      • Bone metastases
      • Brain metastases
      • Hepatic metastases
      • Any nonpulmonary visceral metastases (i.e., skin, spleen)

• Previously untreated disease

• Measurable or evaluable disease

PATIENT CHARACTERISTICS:

• WBC ≥ 3,000/mm^3
• Platelet count ≥ 100,000/mm^3
• Creatinine normal or creatinine clearance > 50 mL/min (unless renal dysfunction is due to tumor obstructing the ureters)
• AST and ALT ≤ 3 times ULN
• Bilirubin ≤ 2.0 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No concurrent malignancy except for nonmelanoma skin cancer
• No known HIV positivity
• No active infections

PRIOR CONCURRENT THERAPY:

• Recovered from prior surgery
• More than 30 days since prior radiotherapy and recovered (unless evidence of progressive disease has been documented)
• No prior chemotherapy
• No other concurrent cytotoxic therapy
• Concurrent radiotherapy and surgery allowed for treatment of brain metastases

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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60 participants in 1 patient group

Paclitaxel, Ifosfamide, and Cisplatin

Experimental group

Description:

-Paclitaxel is administered first, 120 mg/m2 on days 1 and 2 every three weeks for four cycles. Cisplatin is administered at 20 mg/m2 over approximately 30 minutes daily for five days every three weeks for four courses. -The ifosfamide is given last with 1200 mg/m2 daily for five days every three weeks for four cycles.

Treatment:

Biological: pegfilgrastim

Drug: cisplatin

Drug: ifosfamide

Drug: paclitaxel