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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

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ClinicalTrials.gov Identifier: NCT00379340
Recruitment Status : Completed
First Posted : September 21, 2006
Results First Posted : June 14, 2017
Last Update Posted : June 14, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Description
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
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 Favorable Histology 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 or disease Intervention/treatment Phase
Stage III Wilms Tumor With Loss of Heterozygosity (LOH) for 1p and 16q 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

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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 both 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., all 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 or 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 all pulmonary metastases are not eligible for this study. It is recommended that these patients be treated as per the current gold standard of therapy which is chemotherapy according to regimen DD4A (weeks 1-25) and whole lung radiotherapy for 5-14 days beginning in week 1.

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


Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 395 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Newly Diagnosed Higher Risk Favorable Histology Wilms Tumors
Study Start Date : February 2007
Actual Primary Completion Date : October 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Wilms Tumor
U.S. FDA Resources

Arms and Interventions
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Stage IV and rapid complete response (RCR) of lung metastases
Stage IV and rapid complete response (RCR) of lung metastases continuously treated with DD4A after 6 weeks of DD4A
 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
Biological: dactinomycin
Given IV
Other Names:
  • ACT-D
  • actinomycin C1
  • AD
  • Cosmegen
  • DACT
Experimental: Stage IV and slow incomplete response (SIR) of lung metastases
Stage IV and slow incomplete response (SIR) of lung metastases treated with Regimen M after 6 weeks of DD4A
 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
Stage III/IV with LOH 1p and 16q treated with Regimen M
Stage III/IV with LOH 1p and 16q treated with Regimen M
 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
Stage IV with non-lung disease treated with Regimen M
Stage IV with non-lung disease treated with Regimen M
 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
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
Stage IV with lung metastases
Stage IV with lung metastases treated with DD4A for less than 6 weeks and/or response inevaluable at week 6
 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
Biological: dactinomycin
Given IV
Other Names:
  • ACT-D
  • actinomycin C1
  • AD
  • Cosmegen
  • DACT


Outcome Measures
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Primary Outcome Measures :
  1. Event Free Survival Probability [ Time Frame: 4 years ]
    Probability of no relapse, secondary malignancy, or death after 4 year in the study.

  2. Event Free Survival (EFS) Probability [ Time Frame: At 4 years ]
    Probability of no relapse, secondary malignancy, or death after 4 year in the study.

  3. Event Free Survival Probability [ Time Frame: At 4 years ]
    Probability of no relapse, secondary malignancy, or death after 4 year in the study


Secondary Outcome Measures :
  1. Event Free Survival Associated With the Burden of Pulmonary Metastatic Disease [ Time Frame: At 4 years ]
    Probability of no relapse, secondary malignancy, or death after 4 year in the study.


Eligibility Criteria
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Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   up to 29 Years   (Child, Adult)
Sexes Eligible for Study:   All
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
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00379340


  Show 207 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: David Dix, MD Children's Oncology Group
More Information
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00379340     History of Changes
Other Study ID Numbers: AREN0533
NCI-2009-00419 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000496508 ( Other Identifier: Clinical Trials.gov )
U10CA098543 ( U.S. NIH Grant/Contract )
COG-AREN0533 ( Other Identifier: Children's Oncology Group )
First Posted: September 21, 2006    Key Record Dates
Results First Posted: June 14, 2017
Last Update Posted: June 14, 2017
Last Verified: December 2016

Additional relevant MeSH terms:
Neoplasms
Wilms Tumor
Neoplasms, Complex and Mixed
Neoplasms by Histologic Type
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplastic Syndromes, Hereditary
Kidney Diseases
Urologic Diseases
Genetic Diseases, Inborn
Cyclophosphamide
Liposomal doxorubicin
Doxorubicin
 Etoposide
Vincristine
Dactinomycin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors