Combination Chemotherapy Plus Amifostine in Treating Children With Malignant Germ Cell Tumors

High-Dose Cisplatin, Etoposide and Bleomycin (HD-PEB) Combined With Amifostine in Children With High-Risk Malignant Germ Cell Tumors - A POG Pilot Study

RATIONALE: Chemotherapy drugs use different ways to stop tumor cells from dividing so they stop growing or die. Chemoprotective drugs such as amifostine may protect normal cells from the side effects of chemotherapy.

PURPOSE: Phase I trial to study the effectiveness of high-dose cisplatin, etoposide, and bleomycin plus amifostine in treating children who have malignant germ cell tumors.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer; Extragonadal Germ Cell Tumor; Childhood Germ Cell Tumor; Drug/Agent Toxicity by Tissue/Organ
• Intervention / Treatment: Drug: amifostine trihydrate; Drug: etoposide; Drug: cisplatin; Procedure: conventional surgery; Biological: bleomycin sulfate

Detailed Description

OBJECTIVES: I. Evaluate the early efficacy and toxicity profile of high-dose cisplatin, etoposide, bleomycin, and amifostine in children with newly diagnosed, high-risk malignant, extragonadal germ cell tumors. II. Determine whether the use of amifostine can reduce the hematologic and nonhematologic toxic effects of this combination chemotherapy in these patients when compared to similar patients treated on POG-9049/CCG-8881 with the same combination chemotherapy. III. Determine the response rate of patients treated with this regimen.

OUTLINE: Patients undergo surgical biopsy or resection. Patients then receive bleomycin IV over 10 minutes on day 1 and etoposide IV over 1 hour, amifostine IV over 15 minutes, and cisplatin IV over 1 hour on days 1-5. Treatment repeats every 3-4 weeks for 4 courses in the absence of unacceptable toxicity or disease progression. Patients who have no disease after 4 courses of chemotherapy receive no further treatment. Patients who have residual disease undergo second-look surgery. After surgery, patients who still have active tumor receive 2 additional courses of chemotherapy. Those patients who still have tumor after the 2 additional courses may have a third surgery. Patients are followed every month for 6 months, every 2 months for 6 months, every 6 months for 1 year, and then annually thereafter until death.

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study within 1.39 years.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Royal Children's Hospital
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2T 5C7
      • Alberta Children's Hospital
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Children's Hospital
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Hospital for Sick Children
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • Hopital Sainte Justine
    • Montreal, Quebec, Canada, H3H 1P3
      • McGill University Health Center - Montreal Children's Hospital
    • Sainte Foy, Quebec, Canada, GIV 4G2
      • Centre Hospitalier De L'Universite Laval
• Netherlands
  • Groningen, Netherlands, 9713 EZ
    • Academisch Ziekenhuis Groningen
• Puerto Rico
  • Santurce, Puerto Rico, 00912
    • San Jorge Childrens Hospital
• Switzerland
  • Bern, Switzerland, CH 3010
    • Swiss Pediatric Oncology Group Bern
  • Geneva, Switzerland, 1211
    • Clinique de Pediatrie
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • University of Alabama at Birmingham Comprehensive Cancer Center
    • Mobile, Alabama, United States, 36688
      • MBCCOP - Gulf Coast
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Arizona Cancer Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • La Jolla, California, United States, 92093-0658
      • University of California San Diego Cancer Center
    • Palo Alto, California, United States, 94304
      • Lucile Packard Children's Hospital at Stanford
    • Sacramento, California, United States, 95816
      • Sutter Cancer center
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
    • San Diego, California, United States, 92120
      • Kaiser Permanente-Southern California Permanente Medical Group
    • San Diego, California, United States, 92134-3202
      • Naval Medical Center - San Diego
    • San Diego, California, United States, 92123-4282
      • Children's Hospital and Health Center
    • Santa Clara, California, United States, 95051-5386
      • Kaiser Permanente Medical Center - Santa Clara
    • Stanford, California, United States, 94305-5408
      • Stanford University Medical Center
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8028
      • Yale Comprehensive Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20307-5000
      • Walter Reed Army Medical Center
  • Florida
    • Gainesville, Florida, United States, 32610-100277
      • Shands Hospital and Clinics, University of Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic
    • Miami, Florida, United States, 33136
      • Sylvester Cancer Center, University of Miami
    • Miami, Florida, United States, 33176-2197
      • Baptist Hospital of Miami
    • Miami, Florida, United States, 33155
      • Miami Children's Hospital
    • Orlando, Florida, United States, 32803
      • Walt Disney Memorial Cancer Institute
    • Tampa, Florida, United States, 33682-7757
      • CCOP - Florida Pediatric
    • West Palm Beach, Florida, United States, 33407
      • St. Mary's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital - Atlanta
  • Hawaii
    • Honolulu, Hawaii, United States, 96859-5000
      • Tripler Army Medical Center
    • Honolulu, Hawaii, United States, 96813
      • Cancer Research Center of Hawaii
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush-Presbyterian-St. Luke's Medical Center
    • Chicago, Illinois, United States, 60614
      • Children's Memorial Hospital, Chicago
    • Oak Lawn, Illinois, United States, 60453
      • Hope Children's Hospital
    • Peoria, Illinois, United States, 61637
      • Saint Jude Midwest Affiliate
  • Kansas
    • Kansas City, Kansas, United States, 66160-7357
      • University of Kansas Medical Center
    • Wichita, Kansas, United States, 67214-3882
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67214
      • Via Christi Regional Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University School of Medicine
    • New Orleans, Louisiana, United States, 70121
      • CCOP - Ochsner
    • New Orleans, Louisiana, United States, 70112
      • MBCCOP - LSU Health Sciences Center
  • Maine
    • Bangor, Maine, United States, 04401
      • Eastern Maine Medical Center
    • Portland, Maine, United States, 04101
      • Maine Children's Cancer Program
  • Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Baltimore, Maryland, United States, 21201
      • Marlene & Stewart Greenebaum Cancer Center, University of Maryland
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
    • Boston, Massachusetts, United States, 02111
      • Boston Floating Hospital Infants and Children
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Memorial Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
    • Detroit, Michigan, United States, 48236
      • St. John's Hospital and Medical Center
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216-4505
      • University of Mississippi Medical Center
    • Keesler AFB, Mississippi, United States, 39534-2576
      • Keesler Medical Center - Keesler AFB
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri-Columbia Hospital and Clinics
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63104
      • Cardinal Glennon Children's Hospital
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756-0002
      • Norris Cotton Cancer Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Hackensack, New Jersey, United States, 07601
      • CCOP - Northern New Jersey
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico School of Medicine
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • New Hyde Park, New York, United States, 11042
      • Schneider Children's Hospital
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
    • Rochester, New York, United States, 14642
      • University of Rochester Cancer Center
    • Stony Brook, New York, United States, 11790-7775
      • State University of New York Health Sciences Center - Stony Brook
    • Syracuse, New York, United States, 13210
      • State University of New York - Upstate Medical University
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Saint Joseph's Health System
    • Charlotte, North Carolina, United States, 28232-2861
      • Carolinas Medical Center
    • Charlotte, North Carolina, United States, 28233-3549
      • Presbyterian Healthcare
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center
    • Greenville, North Carolina, United States, 27858-4354
      • East Carolina University School of Medicine
    • Winston-Salem, North Carolina, United States, 27157-1082
      • Comprehensive Cancer Center at Wake Forest University
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73126-0307
      • Oklahoma Memorial Hospital
    • Tulsa, Oklahoma, United States, 74136
      • Natalie Warren Bryant Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • CCOP - Columbia River Program
    • Portland, Oregon, United States, 97227
      • Legacy Emanuel Hospital and Health Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19134-1095
      • St. Christopher's Hospital for Children
  • South Carolina
    • Charleston, South Carolina, United States, 29425-0721
      • Medical University of South Carolina
    • Greenville, South Carolina, United States, 29605
      • Children's Hospital of Greenville Hospital System
  • Tennessee
    • Johnson City, Tennessee, United States, 37614-0622
      • James H. Quillen College of Medicine
    • Memphis, Tennessee, United States, 38105-2794
      • Saint Jude Children's Research Hospital
  • Texas
    • Dallas, Texas, United States, 75230
      • Medical City Dallas Hospital
    • Dallas, Texas, United States, 75235-9154
      • Simmons Cancer Center - Dallas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center - Fort Worth
    • Galveston, Texas, United States, 77555-0209
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Lackland Air Force Base, Texas, United States, 78236-5300
      • San Antonio Military Pediatric Cancer and Blood Disorders Center
    • San Antonio, Texas, United States, 78284-7811
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78229-3900
      • MBCCOP - South Texas Pediatric
    • Temple, Texas, United States, 76508
      • Scott and White Clinic
  • Vermont
    • Burlington, Vermont, United States, 05401-3498
      • Vermont Cancer Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Cancer Center at the University of Virginia
    • Falls Church, Virginia, United States, 22042-3300
      • Inova Fairfax Hospital
    • Portsmouth, Virginia, United States, 23708-2197
      • Naval Medical Center, Portsmouth
    • Richmond, Virginia, United States, 23298-0037
      • Massey Cancer Center
    • Roanoke, Virginia, United States, 24029
      • Carilion Roanoke Community Hospital
  • Washington
    • Tacoma, Washington, United States, 98431-5000
      • Madigan Army Medical Center
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • West Virginia University Medical School-Charleston
    • Morgantown, West Virginia, United States, 26506-9300
      • West Virginia University Hospitals
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54307-3508
      • St. Vincent Hospital
    • Milwaukee, Wisconsin, United States, 53226
      • Midwest Children's Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 14 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS: Histologically confirmed, newly diagnosed, high-risk, extracranial germ cell tumors including the following: Yolk sac carcinoma (endodermal sinus tumor) Embryonal carcinoma Choriocarcinoma Teratoma with mixed malignant elements (malignant teratoma) OR Malignant recurrence (stage III or IV) of previously resected stage I extracranial, extragonadal tumor High-risk disease defined as stage III or IV extragonadal tumors Measurable disease by diagnostic imaging

PATIENT CHARACTERISTICS: Age: Under 15 at time of diagnosis Performance status: Not specified Life expectancy: Not specified Hematopoietic: Absolute neutrophil count greater than 750/mm3 Platelet count greater than 75,000/mm3 Hepatic: Not specified Renal: Creatinine normal OR Glomerular filtration rate at least 50% of normal

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy Surgery: See Disease Characteristics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure

Measure Description

Feasibility from Efficacy Standpoint

The hazard rate is constant over 1.39 years, then the probability of the occurrence of a failure within this time interval follows a Poisson distribution. The table below shows the trial feasibility probabilities associated with those failure rates. We define the probability of feasibility as the probability of observing a total of at most less than three failures in 25 patient years of follow-up.

Secondary Outcome Measures

Outcome Measure

Measure Description

Assessment of Reduction in Toxicity

Descriptive statistics will be performed for nephrotoxicity, hematologic and pulmonary toxicities, and inference will be performed for ototoxicity. Frequency tables of the occurrences of toxicities by grade will be tabulated for ANC and platelets. To assess nephrotoxicity and pulmonary toxicity, descriptive statistics will be calculated for GFR and DLCO, respectively. These statistics will be compared to the corresponding summaries on the appropriate population of patients from POG 9049/CCG 8881.

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Neyssa M. Marina, MD, Stanford University

Publications and helpful links

General Publications

• Marina N, Chang KW, Malogolowkin M, London WB, Frazier AL, Womer RB, Rescorla F, Billmire DF, Davis MM, Perlman EJ, Giller R, Lauer SJ, Olson TA; Children's Oncology Group. Amifostine does not protect against the ototoxicity of high-dose cisplatin combined with etoposide and bleomycin in pediatric germ-cell tumors: a Children's Oncology Group study. Cancer. 2005 Aug 15;104(4):841-7. doi: 10.1002/cncr.21218.

Study record dates

Study Major Dates

• Study Start: April 1, 2000
• Primary Completion (Actual): October 1, 2004
• Study Completion (Actual): September 1, 2007

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: December 9, 2003
• First Posted (Estimate): December 10, 2003

Study Record Updates

• Last Update Posted (Estimate): July 4, 2013
• Last Update Submitted That Met QC Criteria: July 3, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: drug/agent toxicity by tissue/organ; childhood teratoma; childhood malignant testicular germ cell tumor; childhood malignant ovarian germ cell tumor; childhood extragonadal germ cell tumor; recurrent childhood malignant germ cell tumor
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Germ Cell and Embryonal; Drug-Related Side Effects and Adverse Reactions; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protective Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Radiation-Protective Agents; Etoposide; Cisplatin; Amifostine; Bleomycin
• Other Study ID Numbers: 9749 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium); POG-9749 (Other Identifier: Pediatric Oncology Group); CDR0000066956 (Other Identifier: Clinical Trials.gov)