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

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.

• pegfilgrastim (Biological)
• cisplatin (Drug)
• ifosfamide (Drug)
• paclitaxel (Drug)

Primary outcomes

• Rate of Complete Response [3 years]: Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions

Secondary outcomes

• Progression-free Survival [Up to 8 years]: Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
• Percentage of Participants With Progression Free Survival [3 years]: Progression Free Survival at 3 years. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
• Number of Patients With Treatment Related Toxicity [3 years]: Toxicity evaluated and graded according to the National Cancer Institute, Version 3.0

Sex: All, ages: 18 Years to 120 Years

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

Participant flow

Outcome results

• Rate of Complete Response (Primary), Count of participants, Participants: Paclitaxel, Ifosfamide, and Cisplatin 38
• Progression-free Survival (Secondary), Median, years: Paclitaxel, Ifosfamide, and Cisplatin 4.4 (1 to 7.6)
• Percentage of Participants With Progression Free Survival (Secondary), Number, percentage of patients: Paclitaxel, Ifosfamide, and Cisplatin 72 (61 to 84)
• Number of Patients With Treatment Related Toxicity (Secondary), Count of participants, Participants: Paclitaxel, Ifosfamide, and Cisplatin 60

Adverse events

Time frame: Day 1, 8 and 15 during each treatment cycle (1 cycle = 21 days). Follow up evaluation will be assessed after 28 days off study as often as every 4-8 weeks for the first year for patients who complete study or withdraw for reason other than progression of disease. For patients who come off study for disease progression, follow-up as often as every 8 weeks for the first year.

Serious adverse events by term

Other adverse events by term

• Darren Feldman, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
• Robert J. Motzer, MD, Principal investigator, Memorial Sloan Kettering Cancer Center