Combination Chemotherapy and Pegfilgrastim in Treating Men With Metastatic Germ Cell Tumors

Accelerated BEP Chemotherapy for Intermediate and High Risk Metastatic Germ Cell Tumor

RATIONALE: Drugs used in chemotherapy, such as bleomycin, etoposide, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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. Giving combination chemotherapy together with pegfilgrastim may kill more tumor cells.

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

Study Overview

• Status: Completed
• Conditions: Testicular Germ Cell Tumor; Teratoma; Extragonadal Germ Cell Tumor
• Intervention / Treatment: Drug: etoposide; Drug: cisplatin; Biological: bleomycin sulfate; Biological: pegfilgrastim

Detailed Description

OBJECTIVES:

Primary

• Determine the feasibility of accelerated treatment comprising bleomycin, etoposide, cisplatin, and pegfilgrastim in men with metastatic germ cell tumors.
• Determine the toxicity of this regimen (particularly with respect to renal, pulmonary, and neurological function) in these patients.

Secondary

• Determine the response rate in patients treated with this regimen.
• Determine the progression-free survival of patients treated with this regimen.

OUTLINE: This is a non-randomized, pilot study.

Patients receive etoposide IV on days 1-3, cisplatin IV on days 1 and 2, and bleomycin IV over 2 hours on days 2, 6, and 10. Patients also receive pegfilgrastim subcutaneously on day 4. Treatment repeats every 14 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 2 years.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • England
    • Cambridge, England, United Kingdom, CB2 2QQ
      • Addenbrooke's Hospital
    • Leeds, England, United Kingdom, LS9 7TF
      • Leeds Cancer Centre at St. James's University Hospital
    • London, England, United Kingdom, EC1A 7BE
      • Saint Bartholomew's Hospital
    • Newcastle-Upon-Tyne, England, United Kingdom, NE4 6BE
      • Northern Centre for Cancer Treatment at Newcastle General Hospital
    • Oxford, England, United Kingdom, OX3 7LJ
      • Churchill Hospital
  • Scotland
    • Edinburgh, Scotland, United Kingdom, EH4 2XU
      • Edinburgh Cancer Centre at Western General Hospital
    • Glasgow, Scotland, United Kingdom, G11 6NT
      • Beatson West of Scotland Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

DISEASE CHARACTERISTICS:

• Patients must fulfill all of the following criteria for 1 of the following diagnoses:

  • Nonseminoma germ cell tumor (intermediate risk)

    • Testis or retroperitoneal primary
    • Abnormal markers (alpha fetoprotein [AFP] > 1,000 and < 10,000 ng/mL, human chorionic gonadotropin [HCG] > 5,000 and < 50,000 IU/L, lactate dehydrogenase [LDH] > 1.5 times and < 10 times upper limit of normal [ULN])
    • No liver, bone, brain, or other nonpulmonary visceral metastasis
    • Histologic confirmation is not required if AFP or HCG are grossly elevated

  • Nonseminoma germ cell tumor (poor prognosis) meeting 1 of the following criteria:

    • Mediastinal primary
    • Nonpulmonary visceral metastases
    • Poor markers (AFP > 10,000 ng/mL, HCG > 50,000 IU/L, LDH > 10 times ULN)
    • Histologic confirmation not required if AFP or HCG are grossly elevated

  • Seminoma (intermediate prognosis)

    • Histological confirmation is required
    • Any primary site
    • Nonpulmonary visceral metastases must be present
    • Normal AFP
    • Any HCG
    • Any LDH

  • Surveillance relapse

    • Must fulfill appropriate criteria above according to initial histology

PATIENT CHARACTERISTICS:

• Neutrophil count ≥ 1,000/mm³
• Platelet count ≥ 100,000/mm³
• Must have adequate renal function (creatinine clearance ≥ 60 mL/min)
• No prior malignancy except basal cell carcinoma

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy or radiotherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Toxicity
Feasibility

Secondary Outcome Measures

Outcome Measure
Response rate
Progression-free survival

Collaborators and Investigators

• Sponsor: Cambridge University Hospitals NHS Foundation Trust
• Investigators: Study Chair: Michael Williams, MD, Cambridge University Hospitals NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start: August 1, 2004
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): January 1, 2009

Study Registration Dates

• First Submitted: March 27, 2007
• First Submitted That Met QC Criteria: March 27, 2007
• First Posted (Estimate): March 28, 2007

Study Record Updates

• Last Update Posted (Estimate): August 7, 2013
• Last Update Submitted That Met QC Criteria: August 6, 2013
• Last Verified: August 1, 2007

More Information

Terms related to this study

• Keywords: stage III malignant testicular germ cell tumor; recurrent malignant testicular germ cell tumor; adult teratoma; testicular embryonal carcinoma; testicular choriocarcinoma; testicular yolk sac tumor; testicular embryonal carcinoma and teratoma; testicular embryonal carcinoma and teratoma with seminoma; testicular embryonal carcinoma and yolk sac tumor; testicular embryonal carcinoma and yolk sac tumor with seminoma; testicular embryonal carcinoma and seminoma; testicular yolk sac tumor and teratoma; testicular yolk sac tumor and teratoma with seminoma; testicular choriocarcinoma and yolk sac tumor; testicular choriocarcinoma and embryonal carcinoma; testicular choriocarcinoma and teratoma; testicular choriocarcinoma and seminoma; recurrent extragonadal non-seminomatous germ cell tumor; recurrent extragonadal seminoma; stage IV extragonadal non-seminomatous germ cell tumor; stage IV extragonadal seminoma; recurrent extragonadal germ cell tumor; testicular immature teratoma; testicular mature teratoma; testicular seminoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Urogenital Neoplasms; Neoplasms by Site; Endocrine System Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Genital Neoplasms, Male; Testicular Diseases; Neoplasms; Neoplasms, Germ Cell and Embryonal; Testicular Neoplasms; Teratoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Etoposide; Cisplatin; Bleomycin
• Other Study ID Numbers: CRCA-CCTC-ACCELERATED-BEP; CDR0000537042 (Registry Identifier: PDQ (Physician Data Query)); EUDRACT-2004-000847-79; EU-20713; ISRCTN18505589 (Registry Identifier: ISRCTN (International Standard Randomised Controlled Trial Number Register))