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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00335556




Registration number
NCT00335556
Ethics application status
Date submitted
8/06/2006
Date registered
12/06/2006
Date last updated
21/07/2017

Titles & IDs
Public title
Combination Chemotherapy, Radiation Therapy, and/or Surgery in Treating Patients With High-Risk Kidney Tumors
Scientific title
Treatment of High Risk Renal Tumors: A Groupwide Phase II Study
Secondary ID [1] 0 0
NCI-2009-00414
Secondary ID [2] 0 0
AREN0321
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Childhood Renal Cell Carcinoma 0 0
Clear Cell Renal Cell Carcinoma 0 0
Clear Cell Sarcoma of the Kidney 0 0
Papillary Renal Cell Carcinoma 0 0
Rhabdoid Tumor of the Kidney 0 0
Stage I Renal Cell Cancer 0 0
Stage I Renal Wilms Tumor 0 0
Stage II Renal Cell Cancer 0 0
Stage II Renal Wilms Tumor 0 0
Stage III Renal Cell Cancer 0 0
Stage III Renal Wilms Tumor 0 0
Stage IV Renal Cell Cancer 0 0
Stage IV Renal Wilms Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Children's - Other
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Doxorubicin Hydrochloride
Treatment: Drugs - Irinotecan Hydrochloride
Treatment: Surgery - Conventional Surgery
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Etoposide
Treatment: Drugs - Carboplatin
Other interventions - Dactinomycin
Treatment: Drugs - Vincristine Sulfate
Treatment: Other - Radiation Therapy
Other interventions - Laboratory Biomarker Analysis

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.

Experimental: Treatment (UH-1) - 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.

Experimental: Treatment (window/UH-1) - 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.

Experimental: Treatment (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.

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.

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.


Treatment: Drugs: Doxorubicin Hydrochloride
Given IV

Treatment: Drugs: Irinotecan Hydrochloride
Given IV

Treatment: Surgery: Conventional Surgery
Patients undergo resection

Treatment: Drugs: Cyclophosphamide
Given IV

Treatment: Drugs: Etoposide
Given IV

Treatment: Drugs: Carboplatin
Given IV

Other interventions: Dactinomycin
Given IV

Treatment: Drugs: Vincristine Sulfate
Given IV

Treatment: Other: Radiation Therapy
Undergo radiotherapy

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Surgery
Intervention code [3] 0 0
Other interventions
Intervention code [4] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-Free Survival of Patients With Diffuse Anaplastic Wilms' Tumor (DAWT) - Compare the outcome of patients treated with alternating CyCE/VDCy chemotherapy (with or without vincristine/irinotecan cycles) to a fixed outcome based on that seen for similar patients treated with NWTS-5 (NCT00002610).
Timepoint [1] 0 0
4 years
Primary outcome [2] 0 0
Long-term Survival of Patients With Stage I-IV Malignant Rhabdoid Tumors - The outcome of these patients will be compared with a fixed outcome based on that seen for similar patients treated with NWTS-5 regimen (NCT00002610).
Timepoint [2] 0 0
4 years
Primary outcome [3] 0 0
Response Rate - Criteria for response assessed by three-dimensional measurement: Complete Response (CR), Disappearance of all index lesions and non-index lesions. No new lesions; Partial Response (PR), At least a 65% decrease in the sum of the volumes of the index lesions. No new lesions; Response rate (RR) = CR+PR of patients who received window therapy.
Timepoint [3] 0 0
Up to 2 months
Primary outcome [4] 0 0
Event Free Survival Probability - Event-free survival will be informally compared to that seem for similar patients treated on NWTS-5 (NCT00002610).
Timepoint [4] 0 0
4 years
Primary outcome [5] 0 0
Toxicity Rate - Percentage of participants with Grade 4 cardiac toxicities, Grade 4 Sinusoidal Obstruction Syndrome (SOS), and treatment-related deaths determined using CTCAE v4.
Timepoint [5] 0 0
Up to 4 years
Secondary outcome [1] 0 0
Number of Patients With INI1 Mutations in Renal and Extrarenal Malignant Rhabdoid Tumor by Fluorescent in Situ Hybridization
Timepoint [1] 0 0
At baseline
Secondary outcome [2] 0 0
Frequency of TP53 Mutations
Timepoint [2] 0 0
At baseline

Eligibility
Key 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
Minimum age
No limit
Maximum age
29 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
John Hunter Children's Hospital - Hunter Regional Mail Centre
Recruitment hospital [2] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [3] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [4] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [5] 0 0
Royal Children's Hospital-Brisbane - Herston
Recruitment hospital [6] 0 0
Women's and Children's Hospital-Adelaide - North Adelaide
Recruitment hospital [7] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [8] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
2310 - Hunter Regional Mail Centre
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
4029 - Herston
Recruitment postcode(s) [5] 0 0
5006 - North Adelaide
Recruitment postcode(s) [6] 0 0
3052 - Parkville
Recruitment postcode(s) [7] 0 0
6008 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Connecticut
Country [7] 0 0
United States of America
State/province [7] 0 0
Delaware
Country [8] 0 0
United States of America
State/province [8] 0 0
District of Columbia
Country [9] 0 0
United States of America
State/province [9] 0 0
Florida
Country [10] 0 0
United States of America
State/province [10] 0 0
Georgia
Country [11] 0 0
United States of America
State/province [11] 0 0
Hawaii
Country [12] 0 0
United States of America
State/province [12] 0 0
Idaho
Country [13] 0 0
United States of America
State/province [13] 0 0
Illinois
Country [14] 0 0
United States of America
State/province [14] 0 0
Indiana
Country [15] 0 0
United States of America
State/province [15] 0 0
Iowa
Country [16] 0 0
United States of America
State/province [16] 0 0
Kentucky
Country [17] 0 0
United States of America
State/province [17] 0 0
Louisiana
Country [18] 0 0
United States of America
State/province [18] 0 0
Maine
Country [19] 0 0
United States of America
State/province [19] 0 0
Maryland
Country [20] 0 0
United States of America
State/province [20] 0 0
Massachusetts
Country [21] 0 0
United States of America
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Michigan
Country [22] 0 0
United States of America
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Minnesota
Country [23] 0 0
United States of America
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Mississippi
Country [24] 0 0
United States of America
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Missouri
Country [25] 0 0
United States of America
State/province [25] 0 0
Nebraska
Country [26] 0 0
United States of America
State/province [26] 0 0
Nevada
Country [27] 0 0
United States of America
State/province [27] 0 0
New Hampshire
Country [28] 0 0
United States of America
State/province [28] 0 0
New Jersey
Country [29] 0 0
United States of America
State/province [29] 0 0
New Mexico
Country [30] 0 0
United States of America
State/province [30] 0 0
New York
Country [31] 0 0
United States of America
State/province [31] 0 0
North Carolina
Country [32] 0 0
United States of America
State/province [32] 0 0
Ohio
Country [33] 0 0
United States of America
State/province [33] 0 0
Oklahoma
Country [34] 0 0
United States of America
State/province [34] 0 0
Oregon
Country [35] 0 0
United States of America
State/province [35] 0 0
Pennsylvania
Country [36] 0 0
United States of America
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Rhode Island
Country [37] 0 0
United States of America
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South Carolina
Country [38] 0 0
United States of America
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South Dakota
Country [39] 0 0
United States of America
State/province [39] 0 0
Tennessee
Country [40] 0 0
United States of America
State/province [40] 0 0
Texas
Country [41] 0 0
United States of America
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Utah
Country [42] 0 0
United States of America
State/province [42] 0 0
Vermont
Country [43] 0 0
United States of America
State/province [43] 0 0
Virginia
Country [44] 0 0
United States of America
State/province [44] 0 0
Washington
Country [45] 0 0
United States of America
State/province [45] 0 0
West Virginia
Country [46] 0 0
United States of America
State/province [46] 0 0
Wisconsin
Country [47] 0 0
Canada
State/province [47] 0 0
Alberta
Country [48] 0 0
Canada
State/province [48] 0 0
British Columbia
Country [49] 0 0
Canada
State/province [49] 0 0
Manitoba
Country [50] 0 0
Canada
State/province [50] 0 0
Newfoundland and Labrador
Country [51] 0 0
Canada
State/province [51] 0 0
Nova Scotia
Country [52] 0 0
Canada
State/province [52] 0 0
Ontario
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Canada
State/province [53] 0 0
Quebec
Country [54] 0 0
Canada
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Saskatchewan
Country [55] 0 0
New Zealand
State/province [55] 0 0
Auckland
Country [56] 0 0
Puerto Rico
State/province [56] 0 0
San Juan

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00335556
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jeffrey Dome, MD
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications