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Vincristine, Dactinomycin, and Doxorubicin With or Without Radiation Therapy or Observation Only in Treating Younger Patients Who Are Undergoing Surgery for Newly Diagnosed Stage I, Stage II, or Stage III Wilms' Tumor

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ClinicalTrials.gov Identifier: NCT00352534
Recruitment Status : Unknown
Verified May 2016 by Children's Oncology Group.
Recruitment status was:  Active, not recruiting
First Posted : July 14, 2006
Results First Posted : May 15, 2017
Last Update Posted : March 25, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Description
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Brief Summary:
This phase III trial is studying vincristine, dactinomycin, and doxorubicin with or without radiation therapy or observation only to see how well they work in treating patients undergoing surgery for newly diagnosed stage I, stage II, or stage III Wilms' tumor. Drugs used in chemotherapy, such as vincristine, dactinomycin, and doxorubicin, 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 these treatments after surgery may kill any tumor cells that remain after surgery. Sometimes, after surgery, the tumor may not need additional treatment until it progresses. In this case, observation may be sufficient.

Condition or disease Intervention/treatment Phase
Stage I Wilms Tumor Stage II Wilms Tumor Stage III Wilms Tumor Procedure: therapeutic conventional surgery Drug: vincristine sulfate Biological: dactinomycin Drug: doxorubicin hydrochloride Radiation: 3-dimensional conformal radiation therapy Phase 3

Detailed Description:

PRIMARY OBJECTIVES:

I. Evaluate the overall and event-free survival of younger patients with newly diagnosed stage I favorable histology Wilms' tumor (< 2 years of age and < 550gms) treated with nephrectomy only (very low risk), or with newly diagnosed stage III favorable histology Wilms tumor with possible nephrectomy followed by vincristine, dactinomycin, doxorubicin hydrochloride, and radiotherapy (standard risk).

SECONDARY OBJECTIVES:

I. Determine the effects of adding doxorubicin hydrochloride to the regimen for patients with stage I or II favorable histology found to have a high-risk biological marker.

II. Determine whether the omission of adjuvant therapy increases the incidence of contralateral kidney lesions in patients with very low-risk disease treated by nephrectomy and observation only.

III. Determine whether the omission of adjuvant therapy increases the incidence of renal failure in patients with very low-risk disease who have metachronous relapse.

IV. Correlate study outcomes in patients with standard-risk disease with biological data from tissue collections on protocol study COG-AREN03B2.

OUTLINE: This is a multicenter study. Patients are stratified according to clinical and biological risk factors (very low risk vs standard risk).

STRATUM I: (very low-risk disease) Patients undergo nephrectomy only. If they meet criteria, they are then observed periodically for 5 years. Patients with recurrent disease undergo surgery (immediate or delayed) and receive chemotherapy as in stratum III. Patients with no metachronous renal disease receive radiotherapy. Patients with metachronous disease undergo renal-sparing surgery and chemotherapy as in stratum III, but no radiotherapy. Treatment continues for up to 25 weeks.

STRATUM II: (standard-risk, stage I or II disease with adverse biological marker) Patients undergo nephrectomy. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1, every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 doses of doxorubicin. Treatment continues for up to 25 weeks.

STRATUM III: (standard-risk, stage III disease) Patients undergo nephrectomy, if feasible, or biopsy. For patients who undergo biopsy only, definitive surgery is undertaken at week 7 or 13. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1 every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 dose of doxorubicin hydrochloride. Patients undergo radiotherapy over 5-7 days after nephrectomy. Treatment continues for up to 25 weeks.

After completion of study treatment, patients are followed periodically for up to 8 years.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 808 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment for Very Low and Standard Risk Favorable Histology Wilms Tumor
Actual Study Start Date : October 30, 2006
Actual Primary Completion Date : December 31, 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Wilms Tumor

Arms and Interventions
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Arm Intervention/treatment
Experimental: Nephrectomy and re-evaluation (very low-risk disease)
Patients undergo nephrectomy only. If they meet criteria, they are then observed periodically for 5 years. Patients with recurrent disease undergo surgery (immediate or delayed) and receive chemotherapy as in stratum III. Patients with no metachronous renal disease receive radiotherapy. Patients with metachronous disease undergo renal-sparing surgery and chemotherapy as in stratum III, but no radiotherapy. Treatment continues for up to 25 weeks.
 Procedure: therapeutic conventional surgery
Undergo surgery

Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS

Biological: dactinomycin
Given IV
Other Names:
  • ACT-D
  • actinomycin C1
  • AD
  • Cosmegen
  • DACT

Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF

Radiation: 3-dimensional conformal radiation therapy
Patients undergo radiotherapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Experimental: Nephrectomy, chemotherapy (standard-risk, stg I or II)
Patients undergo nephrectomy. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1, every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 doses of doxorubicin. Treatment continues for up to 25 weeks.
 Procedure: therapeutic conventional surgery
Undergo surgery

Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS

Biological: dactinomycin
Given IV
Other Names:
  • ACT-D
  • actinomycin C1
  • AD
  • Cosmegen
  • DACT

Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF

Radiation: 3-dimensional conformal radiation therapy
Patients undergo radiotherapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Experimental: Nephrectomy/biopsy, chemotherapy (standard-risk, stage III)
Patients undergo nephrectomy, if feasible, or biopsy. For patients who undergo biopsy only, definitive surgery is undertaken at week 7 or 13. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1 every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 dose of doxorubicin hydrochloride. Patients undergo radiotherapy over 5-7 days after nephrectomy. Treatment continues for up to 25 weeks.
 Procedure: therapeutic conventional surgery
Undergo surgery

Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS

Biological: dactinomycin
Given IV
Other Names:
  • ACT-D
  • actinomycin C1
  • AD
  • Cosmegen
  • DACT

Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF

Radiation: 3-dimensional conformal radiation therapy
Patients undergo radiotherapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT


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. Overall Survival (OS) Probability [ Time Frame: 4 years ]
    Probability of being alive after 4 years in the study.


Secondary Outcome Measures :
  1. Incidence of Contralateral Kidney Lesions [ Time Frame: During follow-up ]
    Number of contralateral kidney lesions during follow-up.

  2. Incidence of Renal Failure [ Time Frame: During follow-up ]
    Number of renal failures defined as requiring dialysis or renal transplant as determined by low GFR during follow-up


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.


Layout table for eligibility information
Ages Eligible for Study:   up to 29 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed Wilms' tumor

    • Newly diagnosed stage I-III disease
    • Favorable histology
  • No moderate- or high-risk Wilms' predisposition syndromes

  • Must meet 1 of the following disease stratification categories:

    • Very low-risk disease

      • Stage I disease
      • Age < 2 years
      • Tumor weight < 550 g
      • Regional lymph nodes histologically negative (must have been sampled)
      • No pulmonary metastases on CT scan of chest
      • No synchronous bilateral Wilms tumors (Stage V)

      • Not predisposed to develop bilateral Wilms tumors, defined as unilateral Wilms tumor and any of the following:

        • Aniridia
        • Beckwith-Wiedemann syndrome
        • Simpson-Golabi-Behmel syndrome
        • Denys-Drash syndrome or other associated genito-urinary anomalies
        • Multicentric WT or unilateral WT with contralateral nephrogenic rest(s) in a child < 1 year of age
        • Diffuse hyperplastic perilobar nephroblastomatosis

    • Standard-risk disease meeting 1 of the following criteria:

      • Disease does not require radiotherapy

        • LOH at chromosomes 1p and 16q for stage I or II

        • Stage I disease meeting 1 of the following criteria:

          • Age ≥ 2 years to age < 30 years
          • Tumor weight ≥ 500 g

        • Stage II disease

          • Age < 30 years
          • Any tumor weight

      • Disease requires radiotherapy

        • No LOH at chromosomes 1p and 16q*
        • Stage III disease
  • Must be enrolled on protocol COG-AREN03B2
  • Karnofsky performance status (PS) 50-100% for patients > 16 years old
  • Lansky PS 50-100% for patients ≤ 16 years old
  • Bilirubin (direct) ≤ 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 (standard-risk disease)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patient must use effective contraception

  • No prior tumor-directed chemotherapy or radiotherapy

    • Patients transferring from AREN03B2 with LOH 1p and 16q allowed
Contacts and Locations
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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): NCT00352534


Locations
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Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Conrad Fernandez, MD Children's Oncology Group
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00352534    
Other Study ID Numbers: AREN0532
NCI-2009-01067 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000487540 ( Other Identifier: ClinicalTrials.gov )
AREN0532 ( Other Identifier: Children's Oncology Group )
AREN0532 ( Other Identifier: CTEP )
U10CA098543 ( U.S. NIH Grant/Contract )
First Posted: July 14, 2006    Key Record Dates
Results First Posted: May 15, 2017
Last Update Posted: March 25, 2020
Last Verified: May 2016
Additional relevant MeSH terms:
Layout table for MeSH terms
Wilms Tumor
Neoplasms
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
Dactinomycin
Cactinomycin
Doxorubicin
 Liposomal doxorubicin
Vincristine
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Anti-Bacterial Agents
Anti-Infective Agents
Protein Synthesis Inhibitors