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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00335556
First received: June 8, 2006
Last updated: February 12, 2014
Last verified: February 2014

June 8, 2006
February 12, 2014
June 2006
June 2016   (final data collection date for primary outcome measure)
  • Event-free survival of patients with diffuse anaplastic Wilms' tumor (DAWT) treated with HU-1 [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Design based on work by Bryant and Day (Biometrics 51:1372-83, 1995), with parameters.
  • Event-free survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 abnormalities, and infection. Each of these adverse events will be monitored separately. A true rate of 1% for the entire treatment period is considered acceptable, whereas a rate of 5.5% would not be.
Not Provided
Complete list of historical versions of study NCT00335556 on ClinicalTrials.gov Archive Site
  • Frequency of INI1 mutations in renal and extrarenal malignant rhabdoid tumor by fluorescent in situ hybridization [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    The biology studies will be hypothesis-generating and descriptive; they do not have a statistical design.
Not Provided
Not Provided
Not Provided
 
Combination Chemotherapy, Radiation Therapy, and/or Surgery in Treating Patients With High-Risk Kidney Tumors
Treatment of High Risk Renal Tumors: A Groupwide Phase II Study

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.

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 or distantly metastatic RCC treated according to institutional preference.

V. Correlate histologic and molecular cytogenetic findings with outcome in pediatric RCC.

VI. Evaluate the frequency of germline and inherited INI1 mutations in renal and extrarenal MRT and correlate the presence of detectable INI1 mutation with clinical outcome.

VII. Determine the frequency of TP53 mutations in anaplastic Wilms' tumor and correlate the presence of detectable TP53 mutation with clinical outcome.

OUTLINE: This is a multicenter study. Patients are assigned to 1 of 6 treatment regimens according to tumor histology, stage of disease, and response to treatment.

SURGERY (renal cell carcinoma [RCC]): Patients with completely resectable stage I-IV RCC undergo surgical resection. Patients with incompletely resectable stage III-IV RCC undergo treatment as per physician's choice.

REGIMEN UH-1 (stage II-III or stage IV [with no measurable disease] diffuse anaplastic Wilms' tumor [DAWT], stage I-IV malignant rhabdoid tumor [MRT], stage IV focal anaplastic Wilms' tumor [FAWT], or stage IV clear cell sarcoma of the kidney [CCSK]): Patients receive vincristine IV on day 1 in weeks 1-3, 10-12, 13-15, 22-24, and 28-30; doxorubicin hydrochloride IV over 15 minutes on day 1 and cyclophosphamide (CPM2) IV over 15-30 minutes on day 1 in weeks 1, 10, 13, 22, and 28; and cyclophosphamide (at lower doses [CPM1]) IV over 1 hour and etoposide IV over 1 hour on days 1-4 and carboplatin IV over 1 hour on day 1 in weeks 4, 7, 16, 19, and 25. Patients whose primary tumors were initially resected undergo radiotherapy once daily 5 days a week for 4-5½ weeks beginning on day 1 in week 1. Patients with delayed primary tumor resection undergo radiotherapy beginning on day 1 in week 13. If the primary tumor was not previously resected, patients undergo resection, if feasible, in week 13. Patients with unresectable CCSK receive no further study therapy.

IRINOTECAN/VINCRISTINE WINDOW THERAPY* (stage IV DAWT with measurable disease at diagnosis): Patients receive vincristine IV on day 1 and irinotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 1 and 2. Patients with progressive disease (PD) are treated with regimen UH-1. Patients with stable disease (SD), partial response (PR), or complete response (CR) receive another course of irinotecan hydrochloride/vincristine window therapy beginning on day 22. After the second course, patients with SD or PD are treated with regimen UH-1 and patients with PR or CR are treated with regimen UH-2.

NOTE: *Patients who are eligible for but who are unwilling to receive window therapy, receive therapy on regimen UH-1.

REGIMEN UH-2 (DAWT with CR/PR to irinotecan hydrochloride/vincristine window therapy): Patients receive vincristine on day 1 in weeks 1-3, 10, 11, 16-21, 25, 26, 28-30, and 34-36 and doxorubicin hydrochloride and CPM2 as in regimen UH-1 in weeks 1, 16, 19, 28, and 34. Patients also receive CPM1, etoposide, and carboplatin as in regimen UH-1 in weeks 4, 7, 13, 22, and 31 and irinotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 10, 11, 25, and 26. Patients whose primary tumors were initially resected undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 1. Patients with delayed primary tumor resection undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 7. If the primary tumor was not previously resected, patients undergo resection, if feasible, in week 7.

REGIMEN I (stage I-III CCSK): Patients receive vincristine IV on day 1 in weeks 1-3, 5-9, 8-9, 11-14, 19, and 25; doxorubicin hydrochloride IV over 15 minutes on day 1 and cyclophosphamide IV over 1 hour on days 1-3 in weeks 1, 7, 13, 19, and 25; and cyclophosphamide IV and etoposide IV on days 1-5 in weeks 4, 10, 16, and 22. Patients whose primary tumors were initially resected (except those with stage I CCSK) undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 1. Patients with delayed primary tumor resection undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 13. If the primary tumor was not previously resected, patients undergo resection, if feasible, in week 13.

REGIMEN DD-4A (stage I DAWT or stages I-III FAWT): Patients receive dactinomycin IV over 1-5 minutes on day 1 in weeks 1, 7, 13, 19, and 25; vincristine IV on day 1 in weeks 1-10, 13, 16, 19, 22, and 25; and doxorubicin hydrochloride IV over 15 minutes on day 1 in weeks 4,10, 16, and 22. Patients whose primary tumors were initially resected undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 1. Patients with delayed primary tumor resection undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 13. If the primary tumor was not previously resected, patients undergo resection, if feasible, in week 13. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for at least 3 years.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Childhood Renal Cell Carcinoma
  • Clear Cell Renal Cell Carcinoma
  • Clear Cell Sarcoma of the Kidney
  • Papillary Renal Cell Carcinoma
  • Rhabdoid Tumor of the Kidney
  • Stage I Renal Cell Cancer
  • Stage I Wilms Tumor
  • Stage II Renal Cell Cancer
  • Stage II Wilms Tumor
  • Stage III Renal Cell Cancer
  • Stage III Wilms Tumor
  • Stage IV Renal Cell Cancer
  • Stage IV Wilms Tumor
  • Drug: doxorubicin hydrochloride
    Given IV
    Other Names:
    • ADM
    • ADR
    • Adria
    • Adriamycin PFS
    • Adriamycin RDF
  • Drug: irinotecan hydrochloride
    Given IV
    Other Names:
    • Campto
    • Camptosar
    • CPT-11
    • irinotecan
    • U-101440E
  • Procedure: conventional surgery
    Patients undergo resection
    Other Name: surgery, conventional
  • Drug: cyclophosphamide
    Given IV
    Other Names:
    • CPM
    • CTX
    • Cytoxan
    • Endoxan
    • Endoxana
  • Drug: etoposide
    Given IV
    Other Names:
    • EPEG
    • VP-16
    • VP-16-213
  • Drug: carboplatin
    Given IV
    Other Names:
    • Carboplat
    • CBDCA
    • JM-8
    • Paraplat
    • Paraplatin
  • Biological: dactinomycin
    Given IV
    Other Names:
    • ACT-D
    • actinomycin C1
    • AD
    • Cosmegen
    • DACT
  • Drug: vincristine sulfate
    Given IV
    Other Names:
    • leurocristine sulfate
    • VCR
    • Vincasar PFS
  • Radiation: radiation therapy
    Undergo radiotherapy
    Other Names:
    • irradiation
    • radiotherapy
    • therapy, radiation
  • Other: laboratory biomarker analysis
    Correlative studies
  • Experimental: Surgery
    Patients with completely resectable stage I-IV RCC undergo surgical resection. Patients with incompletely resectable stage III-IV RCC undergo treatment as per physician's choice.
    Intervention: Procedure: conventional surgery
  • Experimental: Treatment (HU regimen)
    Patients receive combination chemotherapy comprising vincristine, doxorubicin hydrochloride, cyclophosphamide, etoposide, and carboplatin. Patients whose primary tumors were initially resected undergo radiotherapy once daily 5 days a week for 4-5½ weeks beginning on day 1 in week 1. Patients with delayed primary tumor resection undergo radiotherapy beginning on day 1 in week 13. If the primary tumor was not previously resected, patients undergo resection, if feasible, in week 13. Patients with unresectable clear cell sarcoma of the kidney (CCSK) receive no further study therapy.
    Interventions:
    • Drug: doxorubicin hydrochloride
    • Procedure: conventional surgery
    • Drug: cyclophosphamide
    • Drug: etoposide
    • Drug: carboplatin
    • Drug: vincristine sulfate
    • Radiation: radiation therapy
    • Other: laboratory biomarker analysis
  • Experimental: Treatment (Irinotecan/vincristine window therapy)
    Patients receive vincristine IV on days 1 and 8 and irinotecan hydrochloride IV over 30 minutes on days 1-5 and 8-12 (course 1). Patients with progressive disease (PD) are treated with regimen UH-1. Patients with stable disease (SD), partial response (PR), or complete response (CR) receive another course of irinotecan hydrochloride/vincristine window therapy beginning on day 22. After the second course, patients with SD or PD are treated with regimen UH-1 and patients with PR or CR are treated with regimen UH-2.
    Interventions:
    • Drug: doxorubicin hydrochloride
    • Drug: irinotecan hydrochloride
    • Procedure: conventional surgery
    • Drug: cyclophosphamide
    • Drug: etoposide
    • Drug: carboplatin
    • Drug: vincristine sulfate
    • Radiation: radiation therapy
    • Other: laboratory biomarker analysis
  • Experimental: Treatment (regimen UH-2)
    Patients receive combination chemotherapy comprising vincristine, doxorubicin hydrochloride, cyclophosphamide, etoposide, carboplatin, and irinotecan hydrochloride. Patients whose primary tumors were initially resected undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 1. Patients with delayed primary tumor resection undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 7. If the primary tumor was not previously resected, patients undergo resection, if feasible, in week 7.
    Interventions:
    • Drug: doxorubicin hydrochloride
    • Drug: irinotecan hydrochloride
    • Procedure: conventional surgery
    • Drug: etoposide
    • Drug: carboplatin
    • Drug: vincristine sulfate
    • Radiation: radiation therapy
    • Other: laboratory biomarker analysis
  • Experimental: Treatment (regimen I)
    Patients receive vincristine, doxorubicin hydrochloride, cyclophosphamide, and etoposide. Patients whose primary tumors were initially resected (except those with stage I CCSK) undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 1. Patients with delayed primary tumor resection undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 13. If the primary tumor was not previously resected, patients undergo resection, if feasible, in week 13.
    Interventions:
    • Drug: doxorubicin hydrochloride
    • Procedure: conventional surgery
    • Drug: cyclophosphamide
    • Drug: etoposide
    • Drug: vincristine sulfate
    • Radiation: radiation therapy
    • Other: laboratory biomarker analysis
  • Experimental: Treatment (regimen DD-4A)
    Patients receive dactinomycin, vincristine, and doxorubicin hydrochloride. Patients whose primary tumors were initially resected undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 1. Patients with delayed primary tumor resection undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 13. If the primary tumor was not previously resected, patients undergo resection, if feasible, in week 13.
    Interventions:
    • Drug: doxorubicin hydrochloride
    • Procedure: conventional surgery
    • Biological: dactinomycin
    • Drug: vincristine sulfate
    • Radiation: radiation therapy
    • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
291
Not Provided
June 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Newly diagnosed disease of 1 of the following histologic types:

    • Focal anaplastic Wilms' tumor
    • Diffuse anaplastic Wilms' tumor
    • Clear cell sarcoma of the kidney
    • Malignant rhabdoid tumor (renal or extrarenal)
    • Renal cell carcinoma

      • Clear cell
      • Papillary
      • Renal medullary
      • Oncocytoid
      • Sarcomatoid
      • Chromophobe
      • Translocation
      • Collecting duct
      • Carcinoma associated with neuroblastoma
      • Renal cell carcinoma unclassified
  • Specimens/materials must be submitted for central review by Day 7
  • Patients must begin protocol therapy on AREN0321 by Day 14 after surgery or biopsy (surgery/biopsy is Day 0), unless medically contraindicated
  • Karnofsky performance status (PS) must be >= 50 for patients > 16 years if age and Lansky PS must be >= 50 for patients =< 16 years of age
  • Patients must not have received systemic chemotherapy or radiation therapy prior to treatment on this study UNLESS they were enrolled on the AREN0532 or AREN0533 studies and received prenephrectomy chemotherapy for what was originally presumed to be favorable histology Wilms tumor; additionally, patients with pediatric RCC who previously received chemotherapy for another type of malignancy (not the RCC) or non-malignant condition may enroll on the study
  • Total bilirubin =< 1.5 times upper limit of normal (ULN) for age
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST] or serum glutamic pyruvate transaminase (SGPT) (alanine aminotransferase [ ALT]) < 2.5 times ULN for age
  • Shortening fraction of >= 27% by echocardiogram OR ejection fraction of >= 50% by radionuclide angiogram
  • Female patients of childbearing age must have a negative pregnancy test
  • Female patients who are lactating must agree to stop breast-feeding
  • Sexually active patients of childbearing potential must agree to use effective contraception
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Both
up to 29 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada,   New Zealand,   Puerto Rico
 
NCT00335556
AREN0321, NCI-2009-00414, COG-AREN0321, CDR0000472893, AREN0321, AREN0321, U10CA098543
Yes
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Jeffrey Dome, MD Children's Oncology Group
Children's Oncology Group
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP