|Phase II||Biomarker/Laboratory analysis, Treatment||Active||Under 30||NCI, Other||AREN0321|
CDR0000472893, COG-AREN0321, NCT00335556
RATIONALE: 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. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PURPOSE: This phase II trial is studying how well combination chemotherapy, radiation therapy, and/or surgery work in treating patients with high-risk kidney tumors.
Further Study Information
- Evaluate whether a treatment regimen containing cyclophosphamide, carboplatin, and etoposide alternating with vincristine, doxorubicin hydrochloride, and cyclophosphamide (revised regimen UH-1) improves the event-free and overall survival of patients with diffuse anaplastic Wilms tumor (DAWT) as compared to historical controls.
- Evaluate, in a phase II "window" study, the antitumor activity of a combination of vincristine and protracted-schedule irinotecan hydrochloride in patients with metastatic DAWT.
- Evaluate whether revised regimen UH-1 improves the event-free and overall survival of patients with malignant rhabdoid tumor (MRT) as compared to historical controls.
- Maintain the excellent event-free survival of patients with stage I clear cell sarcoma of the kidney (CCSK) without the use of abdominal irradiation.
- Describe the outcomes of patients with stage I DAWT or stages I-III focal anaplastic Wilms tumor (FAWT) treated with vincristine, dactinomycin, doxorubicin hydrochloride, and flank radiation.
- Describe the outcomes of patients with stage IV FAWT or stage IV CCSK treated with revised regimen UH-1.
- Describe event-free and overall survival of children and adolescents with localized renal cell carcinoma (RCC) (including patients with local lymph node involvement) treated with surgical resection without adjuvant therapy.
- Describe response rate, event-free survival, and overall survival of patients with unresectable or distantly metastatic RCC treated according to institutional preference.
- Correlate histologic and molecular cytogenetic findings with outcome in pediatric RCC. (exploratory)
- Evaluate the frequency of germline and inherited INI1 mutations in renal and extrarenal MRT and correlate the presence of detectable INI1 mutation with clinical outcome. (exploratory)
- Determine the frequency of TP53 mutations in anaplastic Wilms tumor and correlate the presence of detectable TP53 mutation with clinical outcome. (exploratory)
OUTLINE: This is a multicenter study. Patients are assigned to 1 of 6 treatment regimens according to tumor histology, stage of disease, and response to treatment.
- Surgery (renal cell carcinoma [RCC]): Patients with completely resectable stage I-IV RCC undergo surgical resection. Patients with incompletely resectable stage III-IV RCC undergo treatment as per physician's choice.
- Patients with initially unresectable or incompletely resected tumors receive chemotherapy and undergo imaging reevaluation after 4 cycles (approximately 12 weeks). If the tumor is deemed resectable at week 13, surgery is performed.
- Revised Regimen UH-1 (stage II-III or stage IV [with no measurable disease] diffuse anaplastic Wilms tumor [DAWT], stage I-IV malignant rhabdoid tumor [MRT], stage IV focal anaplastic Wilms tumor [FAWT], or stage IV clear cell sarcoma of the kidney [CCSK]): Patients receive vincristine IV on day 1 in weeks 1-3, 10-12, 13-15, 22-24, and 28-30; doxorubicin hydrochloride IV over 15 minutes on day 1 and cyclophosphamide (CPM2) IV over 15-30 minutes on day 1 in weeks 1, 10, 13, 22, and 28; and cyclophosphamide (at lower doses [CPM1]) IV over 1 hour and etoposide IV over 1 hour on days 1-4 and carboplatin IV over 1 hour on day 1 in weeks 4, 7, 16, 19, and 25. Patients whose primary tumors were initially resected undergo radiotherapy** once daily, 5 days a week, for 4-5½ weeks beginning on day 1 in week 1. Patients with delayed primary tumor resection undergo radiotherapy** beginning on day 1 in week 13. If the primary tumor was not previously resected, patients undergo resection, if feasible, in week 13. Patients with unresectable CCSK receive no further study therapy.
- Irinotecan/vincristine window therapy* (stage IV DAWT with measurable disease at diagnosis): Patients receive vincristine IV on day 1 and irinotecan hydrochloride IV over 60-90 minutes on days 1-5 in weeks 1 and 2. Patients with progressive disease (PD) are treated with revised regimen UH-1. Patients with stable disease (SD), partial response (PR), or complete response (CR) receive another course of irinotecan hydrochloride/vincristine window therapy beginning on day 22. After the second course, patients with SD or PD are treated with revised regimen UH-1 and patients with PR or CR are treated with revised regimen UH-2.
NOTE: *Patients who are eligible for but who are unwilling to receive window therapy, receive therapy on revised regimen UH-1.
- Some patients will have received pre-operative chemotherapy on AREN0532 or AREN0533 for what was presumed to be favorable histology Wilms tumor. Patients designated to receive revised regimen UH-1 receive this regimen in its entirety starting from week 1, except that the week-28 doxorubicin dose is withheld to maintain a cumulative doxorubicin dose ≤ 225 mg/m^2.
- Revised Regimen UH-2 (DAWT with CR/PR to irinotecan hydrochloride/vincristine window therapy): Patients receive vincristine on day 1 in weeks 1-3, 10, 11, 16-21, 25, 26, 28-30, and 34-36 and doxorubicin hydrochloride and CPM2 as in revised regimen UH-1 in weeks 1, 16, 19, 28, and 34. Patients also receive CPM1, etoposide, and carboplatin as in revised regimen UH-1 in weeks 4, 7, 13, 22, and 31 and irinotecan hydrochloride IV over 60-90 minutes on days 1-5 in weeks 10, 11, 25, and 26. Patients whose primary tumors were initially resected undergo radiotherapy** as in revised regimen UH-1 beginning on day 1 in week 1. Patients with delayed primary tumor resection undergo radiotherapy** as in revised regimen UH-1 beginning on day 1 in week 7. If the primary tumor was not previously resected, patients undergo resection, if feasible, in week 7.
- Regimen I (stage I-III CCSK): Patients receive vincristine IV on day 1 in weeks 1-3, 5-9, 8-9, 11-14, 19, and 25; doxorubicin hydrochloride IV over 15 minutes on day 1 and cyclophosphamide IV over 1 hour on days 1-3 in weeks 1, 7, 13, 19, and 25; and cyclophosphamide IV and etoposide IV on days 1-5 in weeks 4, 10, 16, and 22. Patients whose primary tumors were initially resected (except those with stage I CCSK) undergo radiotherapy** as in revised regimen UH-1 beginning on day 1 in week 1. Patients with delayed primary tumor resection undergo radiotherapy** as in revised regimen UH-1 beginning on day 1 in week 13. If the primary tumor was not previously resected, patients undergo resection, if feasible, in week 13.
- Regimen DD-4A (stage I DAWT or stages I-III FAWT): Patients receive dactinomycin IV over 1-5 minutes on day 1 in weeks 1, 7, 13, 19, and 25; vincristine IV on day 1 in weeks 1-10, 13, 16, 19, 22, and 25; and doxorubicin hydrochloride IV over 15 minutes on day 1 in weeks 4, 10, 16, and 22. Patients whose primary tumors were initially resected undergo radiotherapy** as in revised regimen UH-1 beginning on day 1 in week 1. Patients with delayed primary tumor resection undergo radiotherapy** as in revised regimen UH-1 beginning on day 1 in week 13. If the primary tumor was not previously resected, patients undergo resection, if feasible, in week 13.
- Patients designated to receive Regimen DD-4A may resume this regimen where they left off on the AREN0532 or AREN0533 studies. For example, if a patient received 6 weeks of DD-4A therapy on AREN0532 and then had a nephrectomy showing FAWT, they may transfer to AREN0321 and resume therapy at week 7.
NOTE: **Radiation therapy should be delayed for patients less than 6 months of age.
Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up until the fifth anniversary of the date the patient was enrolled on this study.
PROJECTED ACCRUAL: A total of 295 patients will be accrued for this study.
- Newly diagnosed disease of 1 of the following histologic types:
- Focal anaplastic Wilms' tumor
- Diffuse anaplastic Wilms' tumor
- Clear cell sarcoma of the kidney
- Malignant rhabdoid tumor (renal or extrarenal)
- Renal cell carcinoma
- Clear cell
- Renal medullary
- Collecting duct
- Carcinoma associated with neuroblastoma
- Renal cell carcinoma unclassified
- High-risk disease
- Stage I-IV disease
- No stage V (bilateral) high-risk renal tumors
- Patients with stage IV diffuse anaplastic Wilms tumor are eligible for "window" therapy if the following criteria are met:
- Measurable disease, defined as ≥ 1 lesion that can be measured in 3 dimensions with the longest diameter (which may be in the cranio-caudal dimension) ≥ 1 cm on CT scan or MRI
- No tumors that could potentially cause life-threatening complications with tumor progression, such as tumors with intracranial or intraspinal extension
- No tumors that could compress the airway
- No CNS tumors
- Must be enrolled on COG-AREN03B2
- Karnofsky performance status (PS) 50-100% (> 16 years of age) OR Lansky PS 50-100% (≤ 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 LVEF ≥ 50%
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- No prior systemic chemotherapy or radiation therapy unless enrolled on COG-AREN0532 or COG-AREN0533 clinical trials and received prenephrectomy chemotherapy
- Patients with renal cell carcinoma who received prior chemotherapy for another type of malignancy or non-malignant condition allowed
- Patients who received prior chemotherapy are not eligible for "window" therapy
- No more than 14 days since prior surgery or biopsy unless medically contraindicated or pathological diagnosis requires special studies
- No concurrent aprepitant
Trial Lead Organizations/Sponsors
Children's Oncology GroupNational Cancer Institute
|Jeffrey Stuart Dome||Study Chair|
|Najat Chafic Daw||Study Chair|
|UAB Comprehensive Cancer Center|
|Alyssa T Reddy||Ph: 205-934-0309|
|Miami Children's Hospital|
|Enrique A Escalon||Ph: 305-662-8360|
|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 NCT00335556
ClinicalTrials.gov processed this data on October 17, 2013
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