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

Sponsor

University of Leicester (Other)

Overall Status

Unknown status

CT.gov ID

NCT00047138

Collaborator

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

350

Enrollment

Locations

87.5

Patients Per Site

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Kidney Cancer	Biological: dactinomycin Drug: carboplatin Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: etoposide Drug: vincristine sulfate Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: radiation therapy	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

350 participants

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

Nephroblastoma (Wilms Tumour) Clinical Trial And Study

Study Start Date :

Jan 1, 2001

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 18 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Institut Gustave Roussy	Villejuif		France	94805 CEDEX
2	Universitaetsklinikum des Saarlandes	Homburg		Germany	66421
3	Academisch Medisch Centrum at University of Amsterdam	Amsterdam		Netherlands	1100 DE
4	Royal Marsden - Surrey	Sutton	England	United Kingdom	SM2 5PT

Sponsors and Collaborators

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

Investigators

Study Chair: Jan DeKraker, MD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
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