Combination Chemotherapy With or Without Radiation Therapy in Treating Young Patients With Newly Diagnosed Stage III or Stage IV Wilms' Tumor
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Purpose
This phase III trial is studying how well combination chemotherapy with or without radiation therapy works in treating young patients with newly diagnosed stage III or stage IV Favorable Histology Wilms' tumor. 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. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving more than one drug (combination chemotherapy) with or without radiation therapy may kill more tumor cells.
| Condition | Intervention | Phase |
|---|---|---|
|
Stage III Wilms Tumor With Loss of Heterozygosity (LOH) for 1p and 16q Stage IV Wilms Tumor |
Drug: doxorubicin hydrochloride Drug: liposomal vincristine sulfate Procedure: conventional surgery Radiation: 3-dimensional conformal radiation therapy Biological: dactinomycin Drug: cyclophosphamide Drug: etoposide |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Treatment of Newly Diagnosed Higher Risk Favorable Histology Wilms Tumors |
- EFS of patients with stage IV and rapid complete response (RCR) of lung metastases [ Time Frame: At 4 years ] [ Designated as safety issue: No ]The methods of Woolson to compare the results to the fixed null outcomes as defined above and using an O'Brien-Fleming boundary (truncated at 3 standard deviations) will be used.
- EFS of patients with stage IV and slow incomplete response (SIR) of lung metastases [ Time Frame: At 4 years ] [ Designated as safety issue: No ]The methods of Woolson to compare the results to the fixed null outcomes as defined above and using an O'Brien-Fleming boundary (truncated at 3 standard deviations) will be used.
- EFS of patients with stage IV, non lung disease only, and stage III with LOH 1p and 16q [ Time Frame: At 4 years ] [ Designated as safety issue: No ]
- Correlate between the burden of pulmonary metastatic disease with outcome in patients with stage IV FH Wilms' tumor [ Time Frame: At 4 years ] [ Designated as safety issue: No ]CT scans of the abdomen and of the chest will be submitted in digital format through QARC (chest X-rays will not be requested) and reviewed and classified prospectively. Tumor burden will be compared with relapse-free survival to determine whether pulmonary tumor burden is a prognostic factor
| Enrollment: | 395 |
| Study Start Date: | February 2007 |
| Estimated Primary Completion Date: | July 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment (chemotherapy, surgery, radiotherapy)
REGIMEN DD4A (weeks 1-6): Patients receive dactinomycin IV; liposomal vincristine sulfate IV; and doxorubicin hydrochloride IV. Patients with pulmonary and extra-pulmonary metastases at diagnosis undergo 3-dimensional conformal radiation therapy to all sites of metastatic disease. Patients with initially unresectable tumors at diagnosis are reevaluated at week 6, and if resectable, undergo conventional surgery and then proceed to either regimen DD4A or regimen M based on their pulmonary response at week 6. REGIMEN DD4A (weeks 7-25): Patients receive dactinomycin IV; liposomal vincristine sulfate IV; doxorubicin hydrochloride IV. REGIMEN M (weeks 7-31): Patients receive cyclophosphamide IV; liposomal vincristine sulfate IV; dactinomycin IV; doxorubicin hydrochloride IV and etoposide IV. Patients with pulmonary metastases only who are slow incomplete responders (SIR) also undergo whole lung 3-dimensional conformal radiation therapy.
|
Drug: doxorubicin hydrochloride
Given IV
Other Names:
Drug: liposomal vincristine sulfate
Given IV
Other Names:
Procedure: conventional surgery
Other Name: surgery, conventional
Radiation: 3-dimensional conformal radiation therapy
Other Names:
Biological: dactinomycin
Given IV
Other Names:
Drug: cyclophosphamide
Given IV
Other Names:
Drug: etoposide
Given IV
Other Names:
|
Hide Detailed Description
Detailed Description:
PRIMARY OBJECTIVES:
I. Determine the 4-year event-free survival (EFS) of patients with stage IV favorable histology (FH) Wilms' tumor with pulmonary metastases only who have complete resolution of pulmonary lesions without whole lung irradiation treated with DD4A chemotherapy comprising vincristine, dactinomycin, and doxorubicin hydrochloride.
II. Determine the 4-year EFS of these patients who do not have resolution of pulmonary metastases by week 6 treated with the addition of cyclophosphamide and etoposide to a modified-regimen DD4A (regimen M).
III. Determine the 4-year EFS of patients with stage III or IV FH Wilms' tumor with loss of heterozygosity for chromosomes 1p and 16q treated with regimen M.
SECONDARY OBJECTIVES:
I. Correlate the burden of pulmonary metastatic disease with outcome in patients with stage IV FH Wilms' tumor.
OUTLINE: This is a multicenter study.
REGIMEN DD4A (weeks 1-6): Patients receive dactinomycin IV over 1-5 minutes once in week 1; vincristine IV once in weeks 1-6; and doxorubicin hydrochloride IV over 15 minutes once in week 4 in the absence of disease progression or unacceptable toxicity. Patients with both pulmonary and extra-pulmonary metastases at diagnosis undergo radiotherapy once daily beginning in week 1 and continuing for 5-14 days. After completion of DD4A chemotherapy (week 6), patients undergo evaluation. Patients with stage IV disease and pulmonary metastases only with no loss of heterozygosity (LOH) who are rapid complete responders (RCR) (i.e., all pulmonary metastases disappear) proceed to regimen DD4A (weeks 7-25).
All other patients (i.e., patients with stage III or IV disease and LOH of both 1p and 16q; stage IV disease with pulmonary metastases only who are slow incomplete responders [SIR] [i.e., pulmonary metastases do not disappear]; or stage IV disease with nonpulmonary metastases or with nonpulmonary metastases in combination with pulmonary metastases proceed to regimen M (weeks 7-31).
Patients with initially unresectable or incompletely resected tumors are reevaluated at week 6, and if resectable, undergo surgery and then proceed to either regimen DD4A or regimen M as described above.
REGIMEN DD4A (weeks 7-25): Patients receive dactinomycin IV over 1-5 minutes once in weeks 7, 13, 19, and 25; vincristine IV once in weeks 7-10, 13, 16, 19, 22, and 25; and doxorubicin hydrochloride IV over 15 minutes once in weeks 10, 16, and 22 in the absence of disease progression or unacceptable toxicity.
REGIMEN M (weeks 7-31): Patients receive cyclophosphamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 in weeks 7, 10, 19, and 25; vincristine IV once in weeks 8, 9, 11, 12, 13, 16, 22, 28, and 31; and dactinomycin IV or doxorubicin hydrochloride IV over 15 minutes once in weeks 13, 16, 22, 28, and 31 in the absence of disease progression or unacceptable toxicity. Patients with pulmonary metastases only who are SIR also undergo whole lung radiotherapy once daily beginning in week 7 and continuing for 5-14 days.
NOTE: Patients who begin study treatment after undergoing resection of all pulmonary metastases are not eligible for this study. It is recommended that these patients be treated as per the current gold standard of therapy which is chemotherapy according to regimen DD4A (weeks 1-25) and whole lung radiotherapy for 5-14 days beginning in week 1.
After completion of study treatment, patients are followed periodically for 10 years.
Eligibility| Ages Eligible for Study: | up to 29 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
-
Newly diagnosed Wilms' tumor meeting 1 of the following criteria:
- Stage IV disease with favorable histology with or without loss of heterozygosity (LOH) for 1p and 16q
- Stage III disease with favorable histology with LOH for 1p and 16q transferring from clinical trial COG-AREN0532
- Patients must begin therapy within 14 days after surgery or biopsy, unless medically contraindicated
-
No bilateral Wilms' tumors (stage IV)
- Patients should be referred to COG-AREN0534
- Previously enrolled in clinical trial COG-AREN03B2
- Karnofsky performance status (PS) 50-100% (for patients > 16 years of age) OR Lansky PS 50-100% (for patients ≤ 16 years of age)
- Bilirubin ≤ 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
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No prior tumor-directed chemotherapy or radiotherapy unless transferring from clinical trial COG-AREN0532 OR treatment for emergent issues, as medically indicated
- No concurrent aprepitant
Contacts and LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT00379340
Show 207 Study Locations
| Principal Investigator: | David Dix, MD | Children's Oncology Group |
More Information
No publications provided
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00379340 History of Changes |
| Other Study ID Numbers: | AREN0533, NCI-2009-00419, CDR0000496508, U10CA098543, COG-AREN0533 |
| Study First Received: | September 19, 2006 |
| Last Updated: | October 9, 2014 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Neoplasms Wilms Tumor Genetic Diseases, Inborn Kidney Diseases Kidney Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Complex and Mixed Neoplastic Syndromes, Hereditary Urogenital Neoplasms Urologic Diseases Urologic Neoplasms Cyclophosphamide Dactinomycin Doxorubicin |
Liposomal doxorubicin Vincristine Alkylating Agents Anti-Bacterial Agents Anti-Infective Agents Antibiotics, Antineoplastic Antimitotic Agents Antineoplastic Agents Antineoplastic Agents, Alkylating Antineoplastic Agents, Phytogenic Antirheumatic Agents Enzyme Inhibitors Immunologic Factors Immunosuppressive Agents Mitosis Modulators |
ClinicalTrials.gov processed this record on February 27, 2015