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

June 23, 2014 updated by: University of Leicester

Nephroblastoma (Wilms Tumour) Clinical Trial And Study

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

350

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Villejuif, France, 94805 CEDEX
        • Recruiting
        • Institut Gustave Roussy
        • Contact:
          • Francois Pein, MD
          • Phone Number: 33-1-4211-4339
          • Email: pein@igr.fr
  • Germany
      • Homburg, Germany, 66421
        • Recruiting
        • Universitaetsklinikum des Saarlandes
  • Netherlands
      • Amsterdam, Netherlands, 1100 DE
        • Recruiting
        • Academisch Medisch Centrum at University of Amsterdam
        • Contact:
  • United Kingdom
    • England
      • Sutton, England, United Kingdom, SM2 5PT
        • Recruiting
        • Royal Marsden - Surrey

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 18 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Leicester

Collaborators

Children's Cancer and Leukaemia Group
Gesellschaft fur Padiatrische Onkologie und Hamatologie - Germany
Societe Francaise Oncologie Pediatrique

Investigators

  • Study Chair: Francois Pein, MD, Gustave Roussy, Cancer Campus, Grand Paris
  • Study Chair: Kathy Pritchard-Jones, MD, Royal Marsden NHS Foundation Trust
  • Study Chair: Norbert Graf, Universitaetsklinikum des Saarlandes

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2001

Study Registration Dates

First Submitted

October 3, 2002

First Submitted That Met QC Criteria

January 26, 2003

First Posted (ESTIMATE)

January 27, 2003

Study Record Updates

Last Update Posted (ESTIMATE)

June 24, 2014

Last Update Submitted That Met QC Criteria

June 23, 2014

Last Verified

June 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000257531
  • SIOP-WT-2001
  • SFOP-SIOP-WT-2001
  • CCLG-SIOP-WT-2001
  • GPOH-GERMANY-SIOP-WT-2001
  • EU-20208

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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