Combination Chemotherapy and Surgery in Treating Young Patients With Wilms Tumor

This study has suspended participant recruitment.
(Temporarily stopped for assessment)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00945009
First received: July 22, 2009
Last updated: March 24, 2015
Last verified: March 2015

July 22, 2009
March 24, 2015
July 2009
July 2019   (final data collection date for primary outcome measure)
  • Event-free survival [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Prevention of complete removal of at least one kidney in 50% of patients with bilateral Wilms tumor (BWT) [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
  • Efficacy of chemotherapy in preserving renal units and preventing Wilms tumor development in patients with diffuse hyperplastic perilobular nephrogenic rests [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Facilitation of partial nephrectomy in lieu of total nephrectomy in 25% of patients with unilateral Wilms tumor [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
  • Percentage of patients with bilateral Wilms tumor (BWT) undergoing definitive surgical treatment by week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • 4-year event-free survival [ Designated as safety issue: No ]
  • Prevention of complete removal of at least one kidney in 50% of patients with bilateral Wilms tumor (BWT) [ Designated as safety issue: No ]
  • Efficacy of chemotherapy in preserving renal units and preventing Wilms tumor development in patients with diffuse hyperplastic perilobular nephrogenic rests [ Designated as safety issue: No ]
  • Facilitation of partial nephrectomy in lieu of total nephrectomy in 25% of patients with unilateral Wilms tumor [ Designated as safety issue: No ]
  • Percentage of patients with BWT undergoing definitive surgical treatment by week 12 [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00945009 on ClinicalTrials.gov Archive Site
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Combination Chemotherapy and Surgery in Treating Young Patients With Wilms Tumor
Treatment for Patients With Bilateral, Multicentric, or Bilaterally-Predisposed Unilateral Wilms Tumor

This phase III clinical trial is studying how well combination chemotherapy and surgery work in treating young patients with Bilateral Wilms tumor and children who are a special risk for forming tumors in both kidneys. 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. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving it after surgery may kill any tumor cells that remain after surgery.

OBJECTIVES:

I. To improve 4-year event-free survival (EFS) to 73% for young patients with bilateral Wilms tumor (BWT).

II. To prevent complete removal of at least one kidney in 50% of patients with BWT by using prenephrectomy 3-drug chemotherapy induction with vincristine (vincristine sulfate), dactinomycin, and doxorubicin (doxorubicin hydrochloride).

III. To evaluate the efficacy of chemotherapy in preserving renal units in children with diffuse hyperplastic perilobar nephroblastomatosis (DHPLN) and preventing Wilms tumor development.

IV. To facilitate partial nephrectomy in lieu of nephrectomy in 25% of children with unilateral tumors and aniridia, Beckwith-Wiedemann syndrome (BWS), hemihypertrophy or other overgrowth syndromes, by using prenephrectomy 2-drug chemotherapy induction with vincristine and dactinomycin.

V. To have 75% of patients with BWT undergo definitive surgical treatment by 12 weeks after initiation of chemotherapy.

OUTLINE:

PREOPERATIVE CHEMOTHERAPY: Patients receive preoperative chemotherapy according to radiographic stage.

VAD REGIMEN (stage I-IV bilateral Wilms tumor [BWT] with biopsy revealing favorable histology or no preoperative biopsy; stage I-III BWT with focal anaplasia; stage I BWT with diffuse anaplasia; or high-risk, stage III-IV unilateral Wilms tumor [WT] with contralateral nephrogenic rest [NR] or predisposition syndrome): Patients receive vincristine sulfate intravenously (IV) over 1 minute on days 1, 8, 15, 22, 29, and 36 (weeks 1-6) and dactinomycin IV and doxorubicin hydrochloride IV over 15-120 minutes on days 1 and 22 (weeks 1 and 4).

REVISED UH-1 REGIMEN (stage IV BWT with focal anaplasia; stage II-IV BWT with diffuse anaplasia; or stage I-IV malignant rhabdoid tumor of the kidney): Patients receive vincristine sulfate IV on days 1, 8, and 15 (weeks 1-3); doxorubicin hydrochloride IV over 15-120 minutes on day 1 (week 1); cyclophosphamide IV over 1 hour on day 1 and on days 22-25 (weeks 1 and 4); carboplatin IV over 1 hour on day 22 (week 4); and etoposide phosphate IV over 1 hour on days 22-25 (week 4). -- regimen closed

EE-4A REGIMEN (high-risk, stage I-II unilateral WT with contralateral NR or predisposition syndrome or diffuse hyperplastic perilobar NRs [DHPLNR]): Patients receive vincristine sulfate IV over 1 minute on days 1, 8, 15, 22, 29, and 36 (weeks 1-6) and dactinomycin IV over 1-5 minutes on days 1 and 22 (weeks 1 and 4).

Patients are evaluated at week 6. If partial nephrectomy is feasible, patients proceed to definitive surgery and lymph node sampling followed by postoperative therapy. If partial nephrectomy is not feasible, patients receive additional chemotherapy (as above with the same or a different set of regimen) followed by definitive surgery at week 12 and postoperative therapy OR patients proceed to a different chemotherapy regimen.

POSTOPERATIVE THERAPY: Patients receive postoperative therapy according to histology after preoperative chemotherapy and according to the highest assigned risk for either kidney.

EE-4A regimen (BWT with complete resection of all gross tumors at diagnosis with stage I-II favorable histology; BWT with complete response [CR] by imaging after 6 weeks of preoperative chemotherapy; completely necrotic stage I-II BWT; intermediate-risk stage I BWT; unilateral WT stage I-II with CR by imaging after 6-12 weeks of preoperative chemotherapy; completely necrotic stage I-II unilateral WT; or intermediate-risk stage I-II unilateral WT): Patients receive vincristine sulfate IV over 1 minute on days 43, 50, 57, 64, 85, 106, and 127 (weeks 7-10, 13, 16, and 19) and dactinomycin IV over 1-5 minutes on days 43, 64, 85, 106, and 127 (weeks 7, 10, 13, 16, and 19).

DD-4A REGIMEN (intermediate-risk, stage II BWT; stage I BWT with blastemal predominance; or stage I unilateral WT with blastemal predominance): Patients receive vincristine sulfate IV over 1 minute on days 1, 8, 15, 22, 29, and 36 (weeks 1-6); dactinomycin IV over 1-5 minutes on day 1 (week 1); and doxorubicin hydrochloride IV over 15-120 minutes on day 22 (week 4). Patients then receive vincristine sulfate IV over 1 minute on days 43, 50, 57, 64, 85, 106, 127, 148, and 169 (weeks 7-10, 13, 16, 19, 22, and 25); dactinomycin IV over 1-5 minutes on days 43, 85, 127, and 169 (weeks 7, 13, 19, and 25); and doxorubicin hydrochloride over 15-120 minutes on days 63, 106, and 148 (weeks 10, 16, and 22). Some patients may also undergo radiation therapy.

DD-4A REGIMEN AND RADIATION THERAPY (BWT with complete resection of all gross tumors at diagnosis with stage III-IV favorable histology, completely necrotic stage III-IV BWT; intermediate-risk, stage III-IV BWT; stage I BWT with diffuse anaplasia; stage I-III BWT with focal anaplasia; stage I unilateral WT with diffuse anaplasia; stage I unilateral WT with focal anaplasia; or intermediate-risk, stage III-IV unilateral WT): Patients receive DD-4A regimen as above. Patients also undergo concurrent radiation therapy.

REGIMEN I (stage II BWT with blastemal predominance or stage II unilateral WT with blastemal predominance): Patients receive vincristine sulfate IV over 1 minute on days 43, 50, 57, 71, 78, 85, 92, 127, and 169 (weeks 7-9, 11-14, 19, and 25); doxorubicin hydrochloride IV over 15-120 minutes on days 43, 85, 127, and 169 (weeks 7, 13, 19, and 25); cyclophosphamide IV over 15-30 minutes on days 43, 64, 85, 106, 127, 148, and 169 (weeks 7, 10, 13, 16, 19, 22, and 25); and etoposide phosphate IV over 1 hour on days 64, 106, and 148 (weeks 10, 16, and 22).

REGIMEN I AND RADIATION THERAPY (stage III-IV BWT with blastemal predominance or stage III-IV unilateral WT with blastemal predominance): Patients receive regimen I as above. Patients also undergo concurrent radiation therapy.

REVISED UH-1 REGIMEN AND RADIATION THERAPY (stage IV BWT with focal anaplasia; stage II-IV BWT with diffuse anaplasia; stage IV unilateral WT with focal anaplasia; stage II-IV unilateral WT with diffuse anaplasia; and stage I-IV malignant rhabdoid tumor of the kidney; or DHPLNR with anaplasia): Patients receive vincristine sulfate IV over 1 minute on days 64, 71, 78, 85, 92, 99, 148, 155, 162, 190, 197, and 204 (weeks 10-15, 22-24, and 28-30); doxorubicin hydrochloride IV over 15-120 minutes on days 64, 85, 148, and 190 (weeks 10, 13, 22, and 28); cyclophosphamide IV over 15-30 minutes on days 43-46, 64, 85, 106-109, 127-130, 148, 169-172, and 190 (weeks 7, 10, 13, 16, 19, 22, 25, and 28); carboplatin IV over 1 hour on days 43, 106, 127, and 169 (weeks 7, 16, 19, and 25); and etoposide phosphate IV over 1 hour on days 43-46, 106-109, 127-130, and 169-172 (weeks 7, 16, 19, and 25). Patients also undergo radiation therapy.

VAD REGIMEN (DHPLNR with favorable histology WT with viable elements): Patients receive vincristine sulfate IV over 1 minute on days 43, 50, 57, 64, 71, and 78 (weeks 7-12) and dactinomycin IV over 1-5 minutes and doxorubicin hydrochloride IV over 15-120 minutes on days 43 and 64 (weeks 7 and 10).

After completion of study treatment, patients are followed up periodically for 10 years.

Interventional
Phase 3
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Adult Renal Wilms Tumor
  • Beckwith-Wiedemann Syndrome
  • Childhood Renal Wilms Tumor
  • Diffuse Hyperplastic Perilobar Nephroblastomatosis
  • Hemihypertrophy
  • Stage I Renal Wilms Tumor
  • Stage II Renal Wilms Tumor
  • Stage III Renal Wilms Tumor
  • Stage IV Renal Wilms Tumor
  • Stage V Renal Wilms Tumor
  • Biological: Dactinomycin
    Given IV
    Other Name: Lyovac Cosmegen
  • Drug: Doxorubicin Hydrochloride
    Given IV
  • Drug: Vincristine Sulfate
    Given IV
    Other Names:
    • Kyocristine
    • Oncovin
    • VCR
    • Vincasar
  • Drug: Carboplatin
    Given IV
  • Drug: Cyclophosphamide
    Given IV
  • Drug: Etoposide Phosphate
    Given IV
    Other Names:
    • ETOP
    • Etopophos
  • Radiation: Radiation Therapy
    Undergo radiation therapy
    Other Names:
    • Cancer Radiotherapy
    • Irradiate
    • Irradiated
    • Irradiation
    • RT
  • Procedure: Therapeutic Conventional Surgery
    Undergo surgical resection
  • Procedure: Adjuvant Therapy
    Undergo adjuvant therapy
    Other Name: Adjuvant Therapy
  • Procedure: Neoadjuvant Therapy
    Undergo neoadjuvant therapy
    Other Names:
    • Induction Therapy
    • induction therapy
    • Neoadjuvant
    • Neoadjuvant Therapy
    • Preoperative Therapy
Experimental: Treatment (chemotherapy, radiation therapy, surgery)
See Detailed Description
Interventions:
  • Biological: Dactinomycin
  • Drug: Doxorubicin Hydrochloride
  • Drug: Vincristine Sulfate
  • Drug: Carboplatin
  • Drug: Cyclophosphamide
  • Drug: Etoposide Phosphate
  • Radiation: Radiation Therapy
  • Procedure: Therapeutic Conventional Surgery
  • Procedure: Adjuvant Therapy
  • Procedure: Neoadjuvant Therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Suspended
260
Not Provided
July 2019   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • The patient must have one of the following conditions to be eligible:

    • Synchronous bilateral Wilms tumors*; or
    • Unilateral Wilms tumor and aniridia, Beckwith-Wiedemann Syndrome, idiopathic hemihypertrophy, Simpson-Golabi-Behmel-Syndrome, Denys-Drash Syndrome or other associated genitourinary anomalies associated with bilateral Wilms tumor, such as hypospadias and undescended testis (to be eligible, these patients must not undergo any nephrectomy at diagnosis; note-horseshoe kidney is not associated with bilateral Wilms tumor and these patients should go on the appropriate unilateral Wilms tumor study); or
    • Multicentric Wilms tumor (any age) (to be eligible, these patients must not undergo any nephrectomy at diagnosis); or
    • Unilateral Wilms tumor with contralateral nephrogenic rest(s) (any size) in a child under one year of age (to be eligible, these patients must not undergo any nephrectomy at diagnosis); or
    • Diffuse hyperplastic perilobar nephroblastomatosis (unilateral or bilateral) defined by central radiological review; or
    • Wilms tumor arising in a solitary kidney (patients with metachronous Wilms tumor are not eligible)
    • It is often difficult to distinguish Wilms tumors from nephrogenic rests based on imaging studies and percutaneous biopsies. The AREN0534 study uses the guideline that Wilms tumor with a single lesion 1 cm or greater in the contralateral kidney or multiple lesions (of any size) in the contralateral kidney should be treated on the synchronous bilateral Wilms tumor stratum; patients with an isolated lesion less than 1 cm in the contralateral kidney should be treated on the appropriate study for unilateral Wilms tumor OR on the unilateral Wilms tumor/contralateral nephrogenic rest stratum of this study if they have not undergone nephrectomy and are under one year of age.
    • Loss of heterozygosity (LOH) results—which are used in the unilateral Wilms tumor studies—are not a requirement for enrollment on AREN0534; blood samples can be submitted but will not be used to direct AREN0534 therapy
  • Specimens/materials must be submitted for central review by day 7; for enrollment on AREN0534, unless a biopsy was done, the submission requirements at enrollment on AREN03B2 refer to imaging studies; tissue samples are only required if a surgical procedure (biopsy or nephrectomy) was performed at the time of enrollment on AREN03B2
  • Patients must begin protocol therapy on AREN0534 by day 14 following surgery or diagnosis by initial computed tomography (CT)/magnetic resonance imaging (MRI), unless medically contraindicated
  • Karnofsky performance status must be >= 50% for patients > 16 years of age and Lansky performance status must be >= 50% (for patients =< 16 years of age
  • Patients must not have received systemic chemotherapy or radiation therapy prior to treatment on this study
  • Patients with unilateral Wilms tumor and aniridia, Beckwith-Wiedemann Syndrome, idiopathic hemihypertrophy, Simpson-Golabi-Behmel-Syndrome, Denys-Drash Syndrome or other associated genitourinary anomalies; or multicentric or unilateral Wilms tumor with contralateral nephrogenic rest(s) (any size) in a child under 1 year of age who undergo a nephrectomy at diagnosis are not eligible for this study and should be directed to a unilateral Wilms tumor study
  • Total bilirubin =< 1.5 times upper limit of normal (ULN) for age
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 times upper limit of normal (ULN) for age
  • Shortening fraction >= 27% by echocardiogram, OR ejection fraction >= 50% by radionuclide angiogram

    • (Cardiac function does not need to be assessed in patients who will not receive doxorubicin as part of their initial therapy on this study [i.e., patients who start on regimen EE-4A])
  • Female patients of childbearing age must have a negative pregnancy test
  • Female patients who are lactating must agree to stop breastfeeding
  • Sexually active patients of childbearing potential must agree to use effective contraception
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Both
up to 29 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada,   Israel,   New Zealand,   Puerto Rico
Puerto Rico
 
NCT00945009
AREN0534, NCI-2011-01953, CDR0000649716, AREN0534, AREN0534, U10CA180886, U10CA098543
Yes
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Peter Ehrlich, MD MSC Children's Oncology Group
Children's Oncology Group
March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP