Purpose

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.

Category

IRB Number
20070093HU
NCT Number
NCT00352534
Open to Enrollment
Yes
Sponsor
Children's Oncology Group -



Study Contact

Principal Investigator
Anne-Marie Langevin

Virginia Diaz
(210) 562-9149
diazvr@uthscsa.edu



Eligibility

Eligible Ages
Under29 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Exclusion Criteria

    >

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)
Condition
  • Stage I Wilms Tumor
  • Stage II Wilms Tumor
  • Stage III Wilms Tumor

    • Arm Groups

    ArmDescriptionIntervention
    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.
  • Drug: vincristine sulfate

    Given IV

    Other names:

    • leurocristine sulfate
    • VCR
    • Vincasar PFS

  • Drug: doxorubicin hydrochloride

    Given IV

    Other names:

    • ADM
    • ADR
    • Adria
    • Adriamycin PFS
    • Adriamycin RDF

  • Procedure: therapeutic conventional surgery

    Undergo surgery

  • Biological: dactinomycin

    Given IV

    Other names:

    • ACT-D
    • actinomycin C1
    • AD
    • Cosmegen
    • DACT

  • 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.
  • Drug: vincristine sulfate

    Given IV

    Other names:

    • leurocristine sulfate
    • VCR
    • Vincasar PFS

  • Drug: doxorubicin hydrochloride

    Given IV

    Other names:

    • ADM
    • ADR
    • Adria
    • Adriamycin PFS
    • Adriamycin RDF

  • Procedure: therapeutic conventional surgery

    Undergo surgery

  • Biological: dactinomycin

    Given IV

    Other names:

    • ACT-D
    • actinomycin C1
    • AD
    • Cosmegen
    • DACT

  • 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.
  • Drug: vincristine sulfate

    Given IV

    Other names:

    • leurocristine sulfate
    • VCR
    • Vincasar PFS

  • Drug: doxorubicin hydrochloride

    Given IV

    Other names:

    • ADM
    • ADR
    • Adria
    • Adriamycin PFS
    • Adriamycin RDF

  • Procedure: therapeutic conventional surgery

    Undergo surgery

  • Biological: dactinomycin

    Given IV

    Other names:

    • ACT-D
    • actinomycin C1
    • AD
    • Cosmegen
    • DACT

  • Radiation: 3-dimensional conformal radiation therapy

    Patients undergo radiotherapy

    Other names:

    • 3D conformal radiation therapy
    • 3D-CRT

    •