Combination Chemotherapy in Treating Children With Newly Diagnosed Malignant Germ Cell Tumors

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00066482
First received: August 6, 2003
Last updated: October 15, 2013
Last verified: October 2013
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I trial to study the effect on the body of combining cyclophosphamide with cisplatin, etoposide, and bleomycin in treating children who have newly diagnosed malignant germ cell tumors that are not in the brain and gonads.


Condition Intervention
Childhood Germ Cell Tumor
Extragonadal Germ Cell Tumor
Biological: bleomycin sulfate
Biological: filgrastim
Drug: cisplatin
Drug: cyclophosphamide
Drug: etoposide
Procedure: conventional surgery
Biological: MESNA

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study of Cisplatin, Etoposide, Bleomycin and Escalating Dose Cyclophosphamide Therapy for Children With High Risk Malignant Germ Cell Tumors

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Feasibility of adding cyclophosphamide to a PEB backbone [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Maximum tolerated dose [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    Maximum tolerated dose (MTD) and toxicity profile of cyclophosphamide combined with cisplatin, etoposide, bleomycin (C-PEB) in previously untreated children with high-risk malignant germ cell tumors (MGCT).

  • Estimate the response rate [ Time Frame: Length of study ] [ Designated as safety issue: No ]
    To estimate the response rate in this group of patients to a regimen of cyclophosphamide combined with cisplatin, etoposide, bleomycin (C-PEB).


Enrollment: 19
Study Start Date: July 2004
Primary Completion Date: April 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: combination chemotherapy

Induction therapy: bleomycin sulfate IV over 10-20 minutes on day 1, etoposide IV over 1 hour and cisplatin IV over 4 hours on days 1-5, and cyclophosphamide IV over 1 hour on day 1. MESNA & Filgrastim (G-CSF) subcutaneously once daily beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. 6 patients receive escalating doses of cyclophosphamide until the maximum tolerated dose (MTD) is determined.

Evaluated after 4 courses of therapy. Partial response or stable disease undergo second-look conventional surgery & receive 2 more courses of induction therapy then re-evaluated. Those who do not achieve complete response (CR) after a total of 6 courses may undergo a third conventional surgery. Tumor that cannot be removed are removed from study therapy. Achievement of a CR at anytime are followed monthly for 1 year, every 6 months for 1 year, and then annually for 3 years.

Biological: bleomycin sulfate
Given IV over 10 minutes. Children ≥ 12 months: 15 units/m2/dose Children < 12 months: 0.5 units/kg/dose Day 1 (Week 1, 4, 7, 10)
Other Names:
  • BLEO
  • BLM
  • Blenoxane
  • NSC #125066
Biological: filgrastim
Given SQ once daily 5 micrograms/kg/dose Starting on Day 6 (Week 1, 4, 7, 10) Daily until ANC > 5,000/uL
Other Names:
  • GRANULOCYTE COLONY-STIMULATING FACTOR
  • r-metHuG-CSF
  • G-CSF
  • Filgrastim
  • Neupogen
  • NSC #614629
Drug: cisplatin
Children ≥ 12 months: Given IV over one hour Dose: 20 mg/m2/dose Days 1-5 (Week 1,4,7,10) Children < 12 months: Given IV over 4 hours, 0.67 mg/kg/dose Days 1-5 (Week 1,4,7,10)
Other Names:
  • Cis-diamminedichloroplatinum II
  • Platinol-AQ
  • NSC #119875
Drug: cyclophosphamide
Given IV over 1 hour. Children ≥ 12 months: Level 1: 1.2 g/m2/dose Level 2: 1.8 g/m2/dose Level 3: 2.4 g/m2/dose Children < 12 months: Level 1: 40 mg/kg/dose Level 2: 60 mg/kg/dose Level 3: 80 mg/kg/dose Day 1 (Week 1, 4, 7, 10)
Other Names:
  • Cytoxan
  • NSC #026271
Drug: etoposide
Given IV over 1 hour. Children ≥ 12 months: 100 mg/m2/dose Children < 12 months: 3.3 mg/kg/dose Day 1-5 (Week 1, 4, 7, 10)
Other Names:
  • VP-16
  • VePesid
  • Etopophos
  • NSC #141540
Procedure: conventional surgery
Stage III/IV extragonadal tumors: biopsy followed by a definitive surgical excision after maximal chemotherapy effect, likely after 4 cycles of therapy
Biological: MESNA
Given IV or oral. The total daily MESNA dose is equal to at least 80% of the daily CPM dose. The oral dose of MESNA is 2x the IV dose. Day 1 (Week 1,4,7,10) To be given with CPM.
Other Names:
  • sodium 2-mercaptoethane sulfonate
  • Mesnex
  • NSC #113891

Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose and toxicity profile of cyclophosphamide in combination with bleomycin, etoposide, and cisplatin in pediatric patients with newly diagnosed high-risk extracranial, extragonadal malignant germ cell tumors.
  • Determine the response rate in patients treated with this regimen.

OUTLINE: This is a pilot, multicenter, dose-escalation study of cyclophosphamide.

  • Induction therapy: Patients receive bleomycin IV over 10-20 minutes on day 1, etoposide IV over 1 hour and cisplatin IV over 4 hours on days 1-5, and cyclophosphamide IV over 1 hour on day 1. Patients also receive filgrastim (G-CSF) subcutaneously once daily beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 6 patients receive escalating doses of cyclophosphamide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Patients are evaluated after 4 courses of therapy. Patients with partial response or stable disease undergo second-look surgery, receive 2 more courses of induction therapy, and are then re-evaluated. Patients who do not achieve complete response (CR) after a total of 6 courses may undergo a third surgery. Patients who still have tumor that cannot be removed are removed from study therapy. Patients who achieve a CR at anytime are followed.

Patients are followed monthly for 1 year, every 6 months for 1 year, and then annually for 3 years.

PROJECTED ACCRUAL: A total of 6-18 patients will be accrued for this study within 1.3 years.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed newly diagnosed extracranial germ cell tumors, including 1 of the following types:

    • Yolk sac carcinoma (endodermal sinus tumor)
    • Embryonal carcinoma
    • Choriocarcinoma
    • Teratoma with mixed malignant elements (malignant teratoma)
  • High-risk disease, defined as stage III or IV extragonadal germ cell tumors
  • Must be enrolled on study within 21 days of diagnostic surgical procedure

PATIENT CHARACTERISTICS:

Age

  • 21 and under (at original diagnosis)

Performance status

  • ECOG 0-2

    • Karnofsky 50-100% (in patients over 16 years of age)
    • Lansky 50-100% (in patients 16 years of age and under)

Life expectancy

  • At least 2 months

Hematopoietic

  • Absolute neutrophil count at least 1,000/mm^3
  • Platelet count at least 100,000/mm^3 (transfusion independent)
  • Hemoglobin at least 10.0 g/dL (transfusion allowed)

Hepatic

  • Not specified

Renal

  • Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min OR
  • Creatinine based on age as follows:

    • No greater than 0.8 mg/dL (5 years and under)
    • No greater than 1.0 mg/dL (6-10 years)
    • No greater than 1.2 mg/dL (11-15 years)
    • No greater than 1.5 mg/dL (over 15 years)

Pulmonary

  • FEV_1/FVC greater than 60% OR
  • Children who are uncooperative must meet all of the following criteria:

    • No dyspnea at rest
    • No exercise intolerance
    • Pulse oximetry greater than 94%

Other

  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior radiotherapy

Surgery

  • See Disease Characteristics
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00066482

  Show 98 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Marcio A. Malogolowkin, MD Children's Hospital Los Angeles
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00066482     History of Changes
Other Study ID Numbers: AGCT01P1, CDR0000316244
Study First Received: August 6, 2003
Last Updated: October 15, 2013
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
childhood teratoma
childhood extragonadal germ cell tumor

Additional relevant MeSH terms:
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Mesna
Bleomycin
Etoposide phosphate
Cisplatin
Cyclophosphamide
Etoposide
Lenograstim
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Radiation-Sensitizing Agents
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on July 22, 2014