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Chemotherapy Before and After Surgery in Treating Children With Wilm's Tumor

Primary Purpose

Kidney Cancer

Status
Unknown status
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
dactinomycin
carboplatin
cyclophosphamide
doxorubicin hydrochloride
etoposide
vincristine sulfate
adjuvant therapy
conventional surgery
neoadjuvant therapy
radiation therapy
Sponsored by
University of Leicester
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Kidney Cancer focused on measuring blastema predominant Wilms tumor, epithelial predominant Wilms tumor, mixed cell type Wilms tumor, stage I Wilms tumor, stage II Wilms tumor, stage III Wilms tumor, stage IV Wilms tumor, stage V Wilms tumor, stromal predominant Wilms tumor

Eligibility Criteria

undefined - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Diagnosis of one of the following: Localized disease Unilateral tumor Histologically confirmed Wilms' tumor OR Clinical and ultrasonic characteristics of nephroblastoma No metastasis Age 6 months to 17 years at diagnosis No prior anticancer therapy Metastatic disease Unilateral tumor Histologically confirmed Wilms' tumor OR Clinical and ultrasonic characteristics of nephroblastoma Age 18 and under No prior anticancer therapy Simultaneous bilateral tumors No metastases No recurrent disease No other renal tumors PATIENT CHARACTERISTICS: Age See Disease Characteristics 18 and under Performance status Not specified Life expectancy Not specified Hematopoietic Not specified Hepatic Not specified Renal Not specified Other No social or geographical reasons that would preclude study No other associated pathology that would preclude study PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior chemotherapy Endocrine therapy Not specified Radiotherapy No prior radiotherapy Surgery No prior surgery No requirement for emergency or immediate surgery for any reason

Sites / Locations

  • Institut Gustave RoussyRecruiting
  • Universitaetsklinikum des SaarlandesRecruiting
  • Academisch Medisch Centrum at University of AmsterdamRecruiting
  • Royal Marsden - SurreyRecruiting

Outcomes

Primary Outcome Measures

Event-free survival
Treatment failure, in terms of disease recurrence or death

Secondary Outcome Measures

Full Information

First Posted
October 3, 2002
Last Updated
June 23, 2014
Sponsor
University of Leicester
Collaborators
Societe Francaise Oncologie Pediatrique, Children's Cancer and Leukaemia Group, German Society for Pediatric Oncology and Hematology GPOH gGmbH
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1. Study Identification

Unique Protocol Identification Number
NCT00047138
Brief Title
Chemotherapy Before and After Surgery in Treating Children With Wilm's Tumor
Official Title
Nephroblastoma (Wilms Tumour) Clinical Trial And Study
Study Type
Interventional

2. Study Status

Record Verification Date
June 2009
Overall Recruitment Status
Unknown status
Study Start Date
January 2001 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Leicester
Collaborators
Societe Francaise Oncologie Pediatrique, Children's Cancer and Leukaemia Group, German Society for Pediatric Oncology and Hematology GPOH gGmbH

4. Oversight

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving combination chemotherapy before surgery may shrink the tumor so it can be removed during surgery. Giving more chemotherapy after surgery may kill any remaining tumor cells. It is not yet known which chemotherapy regimen after surgery is most effective in treating Wilm's tumor. PURPOSE: Phase III trial to study the effectiveness of chemotherapy before and after surgery in treating children who have Wilm's tumor.
Detailed Description
OBJECTIVES: Determine the response rate in children with Wilms' tumor treated with pre-operative chemotherapy. Compare the response rate in children with intermediate-risk stage II or III Wilms' tumor treated with or without doxorubicin after surgery. Determine the prognostic significance of histological subtypes in these patients after pre-operative chemotherapy. Determine whether reduced treatment minimizes acute and late toxicity without jeopardizing event-free and overall survival in patients with focal anaplasia or intermediate-risk stage I Wilms' tumor. Determine the prognostic significance of tumor volume and specimen weight after pre-operative chemotherapy and its relation to histological subtype in these patients. Determine the effect of single-dose dactinomycin as pre-operative chemotherapy in these patients. Correlate allele loss at 16q, 1p, and other chromosomal regions with relapse-free and overall survival of patients treated with these regimens. Correlate allele losses with clinical risk factors (e.g., histological appearance and tumor volume) after pre-operative chemotherapy in these patients. Determine laboratory indicators of myocardial damage in patients treated with these regimens. Determine the prognostic significance of the percentage of necrosis after pre-operative chemotherapy, in terms of type and amount of residual viable tumor, in these patients. OUTLINE: This is a partially randomized, multicenter study. Patients are stratified according to country and participating center. Patients with intermediate-risk stage II or III disease are further stratified according to histology (blastemal vs epithelial vs stromal vs mixed). Patients with localized disease receive neoadjuvant therapy comprising vincristine IV on days 1, 8, 15, and 22 and dactinomycin IV on days 1 and 15. Patients undergo surgery during weeks 5 or 6. Patients with low-risk stage I disease receive no further therapy. Adjuvant chemotherapy begins after surgery and within 21 days of last dose of neoadjuvant chemotherapy. Patients with intermediate-risk stage I disease receive vincristine IV on days 1, 8, 15, and 22 and dactinomycin IV on day 7. Patients with intermediate-risk stage II or III disease are randomized to 1 of 2 treatment arms. Arm I: Patients receive vincristine IV weekly for 8 weeks and then on days 1 and 7 of weeks 11, 14, 17, 20, 23, and 26. Patients also receive dactinomycin IV weekly on weeks 2, 5, 8, 11, 14, 17, 20, 23, and 26 and doxorubicin IV over 4-6 hours weekly on weeks 2, 8, 14, 20, and 26. Arm II: Patients receive vincristine and dactinomycin as in arm I. Patients with high-risk stage I disease receive chemotherapy as in arm I. Patients with low-risk stage II disease receive chemotherapy as in arm II. Patients with high-risk stage II or III disease receive cyclophosphamide IV over 1 hour on days 1-3 and doxorubicin IV over 4-6 hours on day 1 on weeks 1, 7, 13, 19, 25, and 31. Patients also receive etoposide IV over 4 hours and carboplatin IV over 1 hour on days 1-3 on weeks 4, 10, 16, 22, 28, and 34. Patients with intermediate-risk stage III or high-risk stage II or III disease also undergo radiotherapy for approximately 3 weeks during chemotherapy. Patients with metastatic disease receive neoadjuvant chemotherapy comprising vincristine IV on day 1 of weeks 1-6, dactinomycin IV on day 1 of weeks 1, 3, and 5, and doxorubicin IV over 4-6 hours on day 1 of weeks 1 and 5. Patients undergo surgery during week 7. Within 2 weeks of surgery patients receive 1 of the following adjuvant chemotherapy regimens: Regimen A (no metastases or completely resected): Patients receive vincristine IV weekly for 8 weeks and then on weeks 11, 12, 14, 15, 17, 18, 20, 21, 23, 24, 26, and 27. Patients also receive dactinomycin IV on day 1 of weeks 2, 5, 8, 11, 14, 17, 20, 23, and 26 and doxorubicin IV over 4-6 hours on weeks 2, 8, 14, and 20. Some patients also undergo radiotherapy concurrently with chemotherapy for approximately 3 weeks. Regimen B (multiple inoperable metastases, incomplete resection, or high-risk primary disease): Patients receive etoposide IV over 4 hours and carboplatin IV over 1 hour on days 1-3 of weeks 4, 10, 13, 16, 22, 25, 28, and 34. Patients also receive cyclophosphamide IV over 1 hour on days 1-3 and doxorubicin IV over 4-6 hours on day 1 of weeks 1, 7, 19, and 31. Some patients also undergo radiotherapy concurrently with chemotherapy for approximately 3 weeks. Patients are followed every 2-3 months for 2 years, every 3-6 months for 1-2 years, and then every 6-12 months thereafter. Peer Reviewed and Funded or Endorsed by Cancer Research UK PROJECTED ACCRUAL: A total of 350 patients (174 per treatment arm) will be accrued for the randomized portion of this study within 7 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Cancer
Keywords
blastema predominant Wilms tumor, epithelial predominant Wilms tumor, mixed cell type Wilms tumor, stage I Wilms tumor, stage II Wilms tumor, stage III Wilms tumor, stage IV Wilms tumor, stage V Wilms tumor, stromal predominant Wilms tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Allocation
Randomized
Enrollment
350 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
dactinomycin
Intervention Type
Drug
Intervention Name(s)
carboplatin
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
doxorubicin hydrochloride
Intervention Type
Drug
Intervention Name(s)
etoposide
Intervention Type
Drug
Intervention Name(s)
vincristine sulfate
Intervention Type
Procedure
Intervention Name(s)
adjuvant therapy
Intervention Type
Procedure
Intervention Name(s)
conventional surgery
Intervention Type
Procedure
Intervention Name(s)
neoadjuvant therapy
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Primary Outcome Measure Information:
Title
Event-free survival
Title
Treatment failure, in terms of disease recurrence or death

10. Eligibility

Sex
All
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of one of the following: Localized disease Unilateral tumor Histologically confirmed Wilms' tumor OR Clinical and ultrasonic characteristics of nephroblastoma No metastasis Age 6 months to 17 years at diagnosis No prior anticancer therapy Metastatic disease Unilateral tumor Histologically confirmed Wilms' tumor OR Clinical and ultrasonic characteristics of nephroblastoma Age 18 and under No prior anticancer therapy Simultaneous bilateral tumors No metastases No recurrent disease No other renal tumors PATIENT CHARACTERISTICS: Age See Disease Characteristics 18 and under Performance status Not specified Life expectancy Not specified Hematopoietic Not specified Hepatic Not specified Renal Not specified Other No social or geographical reasons that would preclude study No other associated pathology that would preclude study PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior chemotherapy Endocrine therapy Not specified Radiotherapy No prior radiotherapy Surgery No prior surgery No requirement for emergency or immediate surgery for any reason
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jan DeKraker, MD
Organizational Affiliation
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Francois Pein, MD
Organizational Affiliation
Gustave Roussy, Cancer Campus, Grand Paris
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Kathy Pritchard-Jones, MD
Organizational Affiliation
Royal Marsden NHS Foundation Trust
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Norbert Graf
Organizational Affiliation
Universitaetsklinikum des Saarlandes
Official's Role
Study Chair
Facility Information:
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805 CEDEX
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Francois Pein, MD
Phone
33-1-4211-4339
Email
pein@igr.fr
Facility Name
Universitaetsklinikum des Saarlandes
City
Homburg
ZIP/Postal Code
66421
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Norbert Graf
Phone
49-6841-162-4000
Facility Name
Academisch Medisch Centrum at University of Amsterdam
City
Amsterdam
ZIP/Postal Code
1100 DE
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jan DeKraker, MD
Phone
31-20-566-9111
Email
j.dekraker@amc.uva.nl
Facility Name
Royal Marsden - Surrey
City
Sutton
State/Province
England
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kathy Pritchard-Jones, MD
Phone
44-20-8661-3452 ext 3498

12. IPD Sharing Statement

Citations:
PubMed Identifier
22513793
Citation
Warmann SW, Nourkami N, Fruhwald M, Leuschner I, Schenk JP, Fuchs J, Graf N. Primary lung metastases in pediatric malignant non-Wilms renal tumors: data from SIOP 93-01/GPOH and SIOP 2001/GPOH. Klin Padiatr. 2012 Apr;224(3):148-52. doi: 10.1055/s-0032-1304600. Epub 2012 Apr 18.
Results Reference
background
PubMed Identifier
21509706
Citation
Furtwangler R, Nourkami N, Alkassar M, von Schweinitz D, Schenk JP, Rube C, Siemer S, Leuschner I, Graf N. Update on relapses in unilateral nephroblastoma registered in 3 consecutive SIOP/GPOH studies - a report from the GPOH-nephroblastoma study group. Klin Padiatr. 2011 May;223(3):113-9. doi: 10.1055/s-0031-1275293. Epub 2011 Apr 20.
Results Reference
background
PubMed Identifier
21370404
Citation
van den Heuvel-Eibrink MM, van Tinteren H, Rehorst H, Coulombe A, Patte C, de Camargo B, de Kraker J, Leuschner I, Lugtenberg R, Pritchard-Jones K, Sandstedt B, Spreafico F, Graf N, Vujanic GM. Malignant rhabdoid tumours of the kidney (MRTKs), registered on recent SIOP protocols from 1993 to 2005: a report of the SIOP renal tumour study group. Pediatr Blood Cancer. 2011 May;56(5):733-7. doi: 10.1002/pbc.22922. Epub 2010 Dec 22.
Results Reference
background
PubMed Identifier
21670612
Citation
Warmann SW, Furtwangler R, Blumenstock G, Armeanu S, Nourkami N, Leuschner I, Schenk JP, Graf N, Fuchs J. Tumor biology influences the prognosis of nephroblastoma patients with primary pulmonary metastases: results from SIOP 93-01/GPOH and SIOP 2001/GPOH. Ann Surg. 2011 Jul;254(1):155-62. doi: 10.1097/SLA.0b013e318222015e.
Results Reference
background
PubMed Identifier
16410128
Citation
Szavay P, Luithle T, Graf N, Furtwangler R, Fuchs J. Primary hepatic metastases in nephroblastoma--a report of the SIOP/GPOH Study. J Pediatr Surg. 2006 Jan;41(1):168-72; discussion 168-72. doi: 10.1016/j.jpedsurg.2005.10.021.
Results Reference
background
PubMed Identifier
21703848
Citation
Smets AM, van Tinteren H, Bergeron C, De Camargo B, Graf N, Pritchard-Jones K, de Kraker J. The contribution of chest CT-scan at diagnosis in children with unilateral Wilms' tumour. Results of the SIOP 2001 study. Eur J Cancer. 2012 May;48(7):1060-5. doi: 10.1016/j.ejca.2011.05.025. Epub 2011 Jun 22.
Results Reference
result
PubMed Identifier
20332316
Citation
Williams RD, Al-Saadi R, Chagtai T, Popov S, Messahel B, Sebire N, Gessler M, Wegert J, Graf N, Leuschner I, Hubank M, Jones C, Vujanic G, Pritchard-Jones K; Children's Cancer and Leukaemia Group; SIOP Wilms' Tumour Biology Group. Subtype-specific FBXW7 mutation and MYCN copy number gain in Wilms' tumor. Clin Cancer Res. 2010 Apr 1;16(7):2036-45. doi: 10.1158/1078-0432.CCR-09-2890. Epub 2010 Mar 23.
Results Reference
result
PubMed Identifier
19231157
Citation
Messahel B, Williams R, Ridolfi A, A'hern R, Warren W, Tinworth L, Hobson R, Al-Saadi R, Whyman G, Brundler MA, Kelsey A, Sebire N, Jones C, Vujanic G, Pritchard-Jones K; Children's Cancer and Leukaemia Group (CCLG). Allele loss at 16q defines poorer prognosis Wilms tumour irrespective of treatment approach in the UKW1-3 clinical trials: a Children's Cancer and Leukaemia Group (CCLG) Study. Eur J Cancer. 2009 Mar;45(5):819-26. doi: 10.1016/j.ejca.2009.01.005. Epub 2009 Feb 21.
Results Reference
result

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Chemotherapy Before and After Surgery in Treating Children With Wilm's Tumor

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