|Phase III||Treatment||Closed||Under 30 at diagnosis||NCI, Other||AREN0532|
NCI-2009-01067, CDR0000487540, COG-AREN0532, U10CA098543, NCT00352534
This phase III trial is studying vincristine, dactinomycin, and doxorubicin with or without radiation therapy or observation only to see how well they work in treating patients undergoing surgery for newly diagnosed stage I, stage II, or stage III Wilms' tumor. Drugs used in chemotherapy, such as vincristine, dactinomycin, and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving these treatments after surgery may kill any tumor cells that remain after surgery. Sometimes, after surgery, the tumor may not need additional treatment until it progresses. In this case, observation may be sufficient.
Further Study Information
I. Evaluate the overall and event-free survival of younger patients with newly diagnosed stage I favorable histology Wilms' tumor (< 2 years of age and < 550gms) treated with nephrectomy only (very low risk), or with newly diagnosed stage III favorable histology Wilms tumor with possible nephrectomy followed by vincristine, dactinomycin, doxorubicin hydrochloride, and radiotherapy (standard risk).
I. Determine the effects of adding doxorubicin hydrochloride to the regimen for patients with stage I or II favorable histology found to have a high-risk biological marker.
II. Determine whether the omission of adjuvant therapy increases the incidence of contralateral kidney lesions in patients with very low-risk disease treated by nephrectomy and observation only.
III. Determine whether the omission of adjuvant therapy increases the incidence of renal failure in patients with very low-risk disease who have metachronous relapse.
IV. Correlate study outcomes in patients with standard-risk disease with biological data from tissue collections on protocol study COG-AREN03B2.
OUTLINE: This is a multicenter study. Patients are stratified according to clinical and biological risk factors (very low risk vs standard risk).
STRATUM I: (very low-risk disease) Patients undergo nephrectomy only. If they meet criteria, they are then observed periodically for 5 years. Patients with recurrent disease undergo surgery (immediate or delayed) and receive chemotherapy as in stratum III. Patients with no metachronous renal disease receive radiotherapy. Patients with metachronous disease undergo renal-sparing surgery and chemotherapy as in stratum III, but no radiotherapy. Treatment continues for up to 25 weeks.
STRATUM II: (standard-risk, stage I or II disease with adverse biological marker) Patients undergo nephrectomy. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1, every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 doses of doxorubicin. Treatment continues for up to 25 weeks.
STRATUM III: (standard-risk, stage III disease) Patients undergo nephrectomy, if feasible, or biopsy. For patients who undergo biopsy only, definitive surgery is undertaken at week 7 or 13. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1 every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 dose of doxorubicin hydrochloride. Patients undergo radiotherapy over 5-7 days after nephrectomy. Treatment continues for up to 25 weeks.
After completion of study treatment, patients are followed periodically for up to 8 years.
- Histologically confirmed Wilms' tumor
- Newly diagnosed stage I-III disease
- Favorable histology
- No moderate- or high-risk Wilms' predisposition syndromes
- Must meet 1 of the following disease stratification categories:
- Very low-risk disease
- Stage I disease
- Age < 2 years
- Tumor weight < 550 g
- Regional lymph nodes histologically negative (must have been sampled)
- No pulmonary metastases on CT scan of chest
- No synchronous bilateral Wilms tumors (Stage V)
- Not predisposed to develop bilateral Wilms tumors, defined as unilateral Wilms tumor and any of the following:
- Beckwith-Wiedemann syndrome
- Simpson-Golabi-Behmel syndrome
- Denys-Drash syndrome or other associated genito-urinary anomalies
- Multicentric WT or unilateral WT with contralateral nephrogenic rest(s) in a child < 1 year of age
- Diffuse hyperplastic perilobar nephroblastomatosis
- Standard-risk disease meeting 1 of the following criteria:
- Disease does not require radiotherapy
- LOH at chromosomes 1p and 16q for stage I or II
- Stage I disease meeting 1 of the following criteria:
- Age ≥ 2 years to age < 30 years
- Tumor weight ≥ 500 g
- Stage II disease
- Age < 30 years
- Any tumor weight
- Disease requires radiotherapy
- No LOH at chromosomes 1p and 16q*
- Stage III disease
- Must be enrolled on protocol COG-AREN03B2
- Karnofsky performance status (PS) 50-100% for patients > 16 years old
- Lansky PS 50-100% for patients ≤ 16 years old
- Bilirubin (direct) ≤ 1.5 times upper limit of normal (ULN)
- AST or ALT < 2.5 times ULN
- Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide angiogram (standard-risk disease)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patient must use effective contraception
- No prior tumor-directed chemotherapy or radiotherapy
- Patients transferring from AREN03B2 with LOH 1p and 16q allowed
Trial Lead Organizations/Sponsors
Children's Oncology GroupNational Cancer Institute
|Conrad Fernandez, MD||Principal Investigator|
|UAB Comprehensive Cancer Center|
|Alyssa T Reddy||Ph: 205-934-0309|
|Children's Oncology Group|
|Conrad V Fernandez||Ph: 902-470-8394|
|Mountain States Tumor Institute at St. Luke's Regional Medical Center|
|Eugenia Chang||Ph: 800-845-4624|
|Western Michigan University School of Medicine Clinics|
|Jeffrey S Lobel||Ph: 800-227-2345|
|Steven L Halpern||Ph: 973-971-5900|
|Legacy Emanuel Hospital and Health Center and Children's Hospital|
|Janice F Olson||Ph: 503-413-2560|
|Cancer Centers of the Carolinas - Faris Road|
|Nichole L Bryant||Ph: 864-241-6251|
|Royal Brisbane and Women's Hospital|
|Helen Irving||Ph: 888-823-5923|
|McMaster Children's Hospital at Hamilton Health Sciences|
|Carol Portwine||Ph: 905-521-2100ext74595|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00352534
ClinicalTrials.gov processed this data on March 03, 2014
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