Clinical Trial: Combination Chemotherapy, Radiation Therapy, and/or Surgery in Treating Patients With High-Risk Kidney Tumors

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Treatment of High Risk Renal Tumors: A Groupwide Phase II Study

Brief Summary: This phase II trial is studying how well combination chemotherapy, radiation therapy, and/or surgery work in treating patients with high-risk kidney tumors. 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. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Evaluate whether a treatment regimen containing cyclophosphamide, carboplatin, and etoposide alternating with vincristine, doxorubicin hydrochloride, and cyclophosphamide (regimen UH-1) improves the event-free and overall survival of patients with diffuse anaplastic Wilms' tumor (DAWT) as compared to historical controls.

II. Evaluate, in a phase II "window" study, the antitumor activity of a combination of vincristine and protracted-schedule irinotecan hydrochloride in patients with metastatic DAWT.

III. Evaluate whether regimen UH-1 improves the event-free and overall survival of patients with malignant rhabdoid tumor (MRT) as compared to historical controls.

IV. Maintain the excellent event-free survival of patients with stage I clear cell sarcoma of the kidney (CCSK) without the use of abdominal irradiation.

SECONDARY OBJECTIVES:

I. Describe the outcomes of patients with stage I DAWT or stages I-III focal anaplastic Wilms' tumor (FAWT) treated with vincristine, dactinomycin, doxorubicin hydrochloride, and flank radiation.

II. Describe the outcomes of patients with stage IV FAWT or stage IV CCSK treated with regimen UH-1.

III. Describe event-free and overall survival of children and adolescents with localized renal cell carcinoma (RCC) (including patients with local lymph node involvement) treated with surgical resection without adjuvant therapy.

IV. Describe response rate, event-free survival, and overall survival of patients with unresectable
Sponsor: Children's Oncology Group

Current Primary Outcome:

  • Event-free survival of patients with diffuse anaplastic Wilms' tumor (DAWT) treated with HU-1 [ Time Frame: Up to 4 years ]
    An analysis plan based on the method of Woolson will be used to monitor outcome for these patients. O'Brien-Fleming boundary (truncated at 3 standard deviations) will be used.
  • Long-term survival of patients with Stage I-IV malignant rhabdoid tumors [ Time Frame: Up to 5 years ]
    The outcome of these patients will be compared with a fixed outcome based on that seen for similar patients treated with NWTS-5 regimen I. An analysis plan will be based on the method of Woolson and an O'Brien-Fleming boundary (truncated at 3 standard deviations).
  • Efficacy of vincristine/irinotecan when delivered in an 6-week window [ Time Frame: Up to 5 years ]
    Design based on work by Bryant and Day (Biometrics 51:1372-83, 1995), with parameters.
  • Event-free survival [ Time Frame: Up to 5 years ]
    Event-free survival will be informally compared to that seem for similar patients treated on NWTS-5.
  • Toxicity as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 35years ]
    Unacceptable toxicity will be defined as treatment-related mortality and Grade 3 or 4 non-hematological toxicity, with the specific exceptions of the following Grade 3 toxicities: anorexia, weight loss, nausea, fatigue, mucositis, diarrhea, fever, electrolyte/metabolic abno

    Original Primary Outcome:

    Current Secondary Outcome:

    • Frequency of INI1 mutations in renal and extrarenal malignant rhabdoid tumor by fluorescent in situ hybridization [ Time Frame: At baseline ]
      The biology studies will be hypothesis-generating and descriptive; they do not have a statistical design.
    • Frequency of TP53 mutations in patients with anaplastic Wilms' tumor by immunohistochemistry [ Time Frame: At baseline ]
      The biology studies will be hypothesis-generating and descriptive; they do not have a statistical design.


    Original Secondary Outcome:

    Information By: Children's Oncology Group

    Dates:
    Date Received: June 8, 2006
    Date Started: June 2006
    Date Completion:
    Last Updated: April 14, 2016
    Last Verified: April 2016