Clinical trial NCT00470366: Combination Chemotherapy and Pegfilgrastim in Treating Patients With Previously Untreated Germ Cell Tumors
Official title: Phase II Trial of Paclitaxel, Ifosfamide, and Cisplatin in Previously Untreated Intermediate and Poor Risk Germ Cell Tumor Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain and Central Nervous System Tumors
Extragonadal Germ Cell Tumor
Ovarian Cancer
Teratoma
Testicular Germ Cell Tumor
Keywords: stage II 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
stage I malignant testicular germ cell tumor
adult central nervous system germ cell tumor
ovarian choriocarcinoma
ovarian dysgerminoma
ovarian embryonal carcinoma
ovarian yolk sac tumor
ovarian immature teratoma
ovarian mature teratoma
ovarian monodermal and highly specialized teratoma
ovarian polyembryoma
ovarian mixed germ cell tumor
stage IV ovarian germ cell tumor
stage IV extragonadal seminoma
stage I extragonadal non-seminomatous germ cell tumor
stage II extragonadal non-seminomatous germ cell tumor
stage III extragonadal non-seminomatous germ cell tumor
stage IV extragonadal non-seminomatous germ cell tumor
adult teratoma
testicular immature teratoma
testicular mature teratoma
stage IA ovarian germ cell tumor
stage IB ovarian germ cell tumor
stage IC ovarian germ cell tumor
stage IIA ovarian germ cell tumor
stage IIB ovarian germ cell tumor
stage IIC ovarian germ cell tumor
stage IIIA ovarian germ cell tumor
stage IIIB ovarian germ cell tumor
stage IIIC ovarian germ cell tumor
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-05-07
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Rate of Complete Response
timeFrame: 3 years
Secondary outcomes:
measure: Progression-free Survival
timeFrame: Up to 8 years
measure: Percentage of Participants With Progression Free Survival
timeFrame: 3 years
measure: Number of Patients With Treatment Related Toxicity
timeFrame: 3 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Darren Feldman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Memorial Sloan Kettering Cancer Center
name: Robert J. Motzer, MD
role: PRINCIPAL_INVESTIGATOR
References: