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

• ClinicalTrials.gov Identifier: NCT00470366
• Recruitment Status: Completed
• First Posted: May 7, 2007
• Results First Posted: October 24, 2017
• Last Update Posted: November 28, 2017
• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Brain and Central Nervous System Tumors; Extragonadal Germ Cell Tumor; Ovarian Cancer; Teratoma; Testicular Germ Cell Tumor	Biological: pegfilgrastim; Drug: cisplatin; Drug: ifosfamide; Drug: paclitaxel	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Paclitaxel, Ifosfamide, and Cisplatin in Previously Untreated Intermediate and Poor Risk Germ Cell Tumor Patients
• Study Start Date: March 2007
• Actual Primary Completion Date: June 2016
• Actual Study Completion Date: June 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Paclitaxel, Ifosfamide, and Cisplatin; -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.	Biological: pegfilgrastim; Drug: cisplatin; Drug: ifosfamide; Drug: paclitaxel

Outcome Measures

Primary Outcome Measures :

1. Rate of Complete Response [ Time Frame: 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 Outcome Measures :

1. Progression-free Survival [ Time Frame: 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
2. Percentage of Participants With Progression Free Survival [ Time Frame: 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
3. Number of Patients With Treatment Related Toxicity [ Time Frame: 3 years ]
   Toxicity evaluated and graded according to the National Cancer Institute, Version 3.0

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, California

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States, 90089-9181

United States, New York

Memorial Sloan-Kettering Cancer Center

New York, New York, United States, 10065

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Darren Feldman, MD; Memorial Sloan Kettering Cancer Center
• Principal Investigator: Robert J. Motzer, MD; Memorial Sloan Kettering Cancer Center

More Information

Additional Information:

Memorial Sloan Kettering Cancer Center 

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00470366
• Other Study ID Numbers: 07-044; MSKCC-07044
• First Posted: May 7, 2007
• Results First Posted: October 24, 2017
• Last Update Posted: November 28, 2017
• Last Verified: June 2016

Keywords provided by Memorial Sloan Kettering Cancer Center:

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

Additional relevant MeSH terms:

Neoplasms, Germ Cell and Embryonal; Nervous System Neoplasms; Central Nervous System Neoplasms; Teratoma; Neoplasms; Neoplasms by Site; Neoplasms by Histologic Type; Nervous System Diseases; Paclitaxel; Ifosfamide; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Alkylating; Alkylating Agents