Trial record 1 of 1 for:    AREN0533
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Combination Chemotherapy With or Without Radiation Therapy in Treating Young Patients With Newly Diagnosed Stage III or Stage IV Wilms' Tumor

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00379340
First received: September 19, 2006
Last updated: June 18, 2013
Last verified: June 2013
  Purpose

This phase III trial is studying how well combination chemotherapy with or without radiation therapy works in treating young patients with newly diagnosed stage III or stage IV Wilms' tumor. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving more than one drug (combination chemotherapy) with or without radiation therapy may kill more tumor cells.


Condition Intervention Phase
Stage III Wilms Tumor
Stage IV Wilms Tumor
Drug: doxorubicin hydrochloride
Drug: liposomal vincristine sulfate
Procedure: conventional surgery
Radiation: 3-dimensional conformal radiation therapy
Biological: dactinomycin
Drug: cyclophosphamide
Drug: etoposide
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Newly Diagnosed Higher Risk Favorable Histology Wilms Tumors

Resource links provided by NLM:


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

Primary Outcome Measures:
  • EFS of patients with stage IV and rapidly completely responding (RCR) lung metastases [ Time Frame: At 4 years ] [ Designated as safety issue: No ]
    The methods of Woolson to compare the results to the fixed null outcomes as defined above and using an O'Brien-Fleming boundary (truncated at 3 standard deviations) will be used.

  • EFS of patients with stage IV and slow incomplete response (SIR) of lung metastases [ Time Frame: At 4 years ] [ Designated as safety issue: No ]
    The methods of Woolson to compare the results to the fixed null outcomes as defined above and using an O'Brien-Fleming boundary (truncated at 3 standard deviations) will be used.

  • EFS of patients with stage IV, non lung disease only and stage III/IV [ Time Frame: At 4 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Correlate between the burden of pulmonary metastatic disease with outcome in patients with stage IV FH Wilms' tumor [ Time Frame: At 4 years ] [ Designated as safety issue: No ]
    CT scans of the abdomen and of the chest will be submitted in digital format through QARC (chest X-rays will not be requested) and reviewed and classified prospectively. Tumor burden will be compared with relapse-free survival to determine whether pulmonary tumor burden is a prognostic factor


Enrollment: 395
Study Start Date: February 2007
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemotherapy, surgery, radiotherapy)
REGIMEN DD4A (weeks 1-6): Patients receive dactinomycin IV; liposomal vincristine sulfate IV; and doxorubicin hydrochloride IV. Patients with pulmonary and extra-pulmonary metastases at diagnosis undergo 3-dimensional conformal radiation therapy. Patients with initially unresectable or incompletely resected tumors are reevaluated at week 6, and if resectable, undergo conventional surgery and then proceed to either regimen DD4A or regimen M. REGIMEN DD4A (weeks 7-25): Patients receive dactinomycin IV; liposomal vincristine sulfate IV; doxorubicin hydrochloride IV and etoposide. REGIMEN M (weeks 7-31): Patients receive cyclophosphamide IV; liposomal vincristine sulfate IV; dactinomycin IV; doxorubicin hydrochloride IV and etoposide. Patients with pulmonary metastases only who are SIR also undergo whole lung 3-dimensional conformal radiation therapy.
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: liposomal vincristine sulfate
Given IV
Other Names:
  • liposomal vincristine
  • Marqibo
  • vincristine liposomal
  • vincristine sulfate liposome injection
Procedure: conventional surgery
Other Name: surgery, conventional
Radiation: 3-dimensional conformal radiation therapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Biological: dactinomycin
Given IV
Other Names:
  • ACT-D
  • actinomycin C1
  • AD
  • Cosmegen
  • DACT
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213

  Hide Detailed Description

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the 4-year event-free survival (EFS) of patients with stage IV favorable histology (FH) Wilms' tumor with pulmonary metastases only who have complete resolution of pulmonary lesions without whole lung irradiation treated with DD4A chemotherapy comprising vincristine, dactinomycin, and doxorubicin hydrochloride.

II. Determine the 4-year EFS of these patients who do not have resolution of pulmonary metastases by week 6 treated with the addition of cyclophosphamide and etoposide to a modified-regimen DD4A (regimen M).

III. Determine the 4-year EFS of patients with stage III or IV FH Wilms' tumor with loss of heterozygosity for chromosomes 1p and 16q treated with regimen M.

SECONDARY OBJECTIVES:

I. Correlate the burden of pulmonary metastatic disease with outcome in patients with stage IV FH Wilms' tumor.

OUTLINE: This is a multicenter study.

REGIMEN DD4A (weeks 1-6): Patients receive dactinomycin IV over 1-5 minutes once in week 1; vincristine IV once in weeks 1-6; and doxorubicin hydrochloride IV over 15 minutes once in week 4 in the absence of disease progression or unacceptable toxicity. Patients with pulmonary and extra-pulmonary metastases at diagnosis undergo radiotherapy once daily beginning in week 1 and continuing for 5-14 days. After completion of DD4A chemotherapy (week 6), patients undergo evaluation. Patients with stage IV disease and pulmonary metastases only with no loss of heterozygosity (LOH) who are rapid complete responders (RCR) (i.e., pulmonary metastases disappear) proceed to regimen DD4A (weeks 7-25).

All other patients (i.e., patients with stage III or IV disease and LOH of both 1p and 16q; stage IV disease with pulmonary metastases only who are slow incomplete responders [SIR] [i.e., pulmonary metastases do not disappear]; or stage IV disease with nonpulmonary metastases or with nonpulmonary metastases in combination with pulmonary metastases) proceed to regimen M (weeks 7-31).

Patients with initially unresectable or incompletely resected tumors are reevaluated at week 6, and if resectable, undergo surgery and then proceed to either regimen DD4A or regimen M as described above.

REGIMEN DD4A (weeks 7-25): Patients receive dactinomycin IV over 1-5 minutes once in weeks 7, 13, 19, and 25; vincristine IV once in weeks 7-10, 13, 16, 19, 22, and 25; and doxorubicin hydrochloride IV over 15 minutes once in weeks 10, 16, and 22 in the absence of disease progression or unacceptable toxicity.

REGIMEN M (weeks 7-31): Patients receive cyclophosphamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 in weeks 7, 10, 19, and 25; vincristine IV once in weeks 8, 9, 11, 12, 13, 16, 22, 28, and 31; and dactinomycin IV and doxorubicin hydrochloride IV over 15 minutes once in weeks 13, 16, 22, 28, and 31 in the absence of disease progression or unacceptable toxicity. Patients with pulmonary metastases only who are SIR also undergo whole lung radiotherapy once daily beginning in week 7 and continuing for 5-14 days.

NOTE: Patients who begin study treatment after undergoing resection of pulmonary metastases are treated according to regimen DD4A (weeks 1-25) and undergo whole lung radiotherapy for 5-14 days beginning in week 1.

After completion of study treatment, patients are followed periodically for 10 years.

  Eligibility

Ages Eligible for Study:   up to 29 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Newly diagnosed Wilms' tumor meeting 1 of the following criteria:

    • Stage IV disease with favorable histology with or without loss of heterozygosity (LOH) for 1p and 16q
    • Stage III disease with favorable histology with LOH for 1p and 16q transferring from clinical trial COG-AREN0532
  • Patients must begin therapy within 14 days after surgery or biopsy, unless medically contraindicated
  • No bilateral Wilms' tumors (stage IV)

    • Patients should be referred to COG-AREN0534
  • Previously enrolled in clinical trial COG-AREN03B2
  • Karnofsky performance status (PS) 50-100% (for patients > 16 years of age) OR Lansky PS 50-100% (for patients ≤ 16 years of age)
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST or ALT < 2.5 times ULN
  • Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide angiogram
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No prior tumor-directed chemotherapy or radiotherapy unless transferring from clinical trial COG-AREN0532 OR treatment for emergent issues, as medically indicated
  • No concurrent aprepitant
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00379340

  Show 207 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: David Dix Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00379340     History of Changes
Other Study ID Numbers: AREN0533, NCI-2009-00419, CDR0000496508, U10CA098543, COG-AREN0533
Study First Received: September 19, 2006
Last Updated: June 18, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Wilms Tumor
Neoplasms, Complex and Mixed
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplastic Syndromes, Hereditary
Kidney Diseases
Urologic Diseases
Genetic Diseases, Inborn
Dactinomycin
Doxorubicin
Etoposide phosphate
Cyclophosphamide
Etoposide
Vincristine
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Anti-Bacterial Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on April 22, 2014