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
  Purpose

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.


Condition Intervention Phase
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
Drug: irinotecan hydrochloride
Procedure: conventional surgery
Drug: cyclophosphamide
Drug: etoposide
Drug: carboplatin
Biological: dactinomycin
Drug: vincristine sulfate
Radiation: radiation therapy
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of High Risk Renal Tumors: A Groupwide Phase II Study

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 291
Study Start Date: June 2006
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Procedure: conventional surgery
Patients undergo resection
Other Name: surgery, conventional
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.
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
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
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: 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.
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
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: 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.
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: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
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: 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.
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
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: 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: 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.
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Procedure: conventional surgery
Patients undergo resection
Other Name: surgery, conventional
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 29 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00335556

  Show 182 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Jeffrey Dome, MD Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00335556     History of Changes
Other Study ID Numbers: AREN0321, NCI-2009-00414, COG-AREN0321, CDR0000472893, AREN0321, AREN0321, U10CA098543
Study First Received: June 8, 2006
Last Updated: February 12, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Kidney Neoplasms
Wilms Tumor
Sarcoma, Clear Cell
Rhabdoid Tumor
Sarcoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Neoplasms, Complex and Mixed
Neoplastic Syndromes, Hereditary
Genetic Diseases, Inborn
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Dactinomycin
Doxorubicin
Etoposide phosphate
Irinotecan
Cyclophosphamide
Etoposide
Vincristine
Carboplatin
Camptothecin

ClinicalTrials.gov processed this record on July 24, 2014