ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    AREN0534
Previous Study | Return to List | Next Study

Combination Chemotherapy and Surgery in Treating Young Patients With Wilms Tumor

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00945009
Recruitment Status : Completed
First Posted : July 23, 2009
Last Update Posted : July 25, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Brief Summary:
This phase III trial studies how well combination chemotherapy and surgery work in treating young patients with Wilms tumor. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. 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.

Condition or disease Intervention/treatment Phase
Adult Kidney Wilms Tumor Beckwith-Wiedemann Syndrome Childhood Kidney Wilms Tumor Diffuse Hyperplastic Perilobar Nephroblastomatosis Hemihypertrophy Rhabdoid Tumor of the Kidney Stage I Kidney Wilms Tumor Stage II Kidney Wilms Tumor Stage III Kidney Wilms Tumor Stage IV Kidney Wilms Tumor Stage V Kidney Wilms Tumor Biological: Dactinomycin Drug: Doxorubicin Hydrochloride Radiation: Radiation Therapy Procedure: Therapeutic Conventional Surgery Drug: Vincristine Sulfate Phase 3

Detailed Description:

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: Patients are assigned to 1 of 3 arms.

ARM 1 (Bilateral Wilms Tumors): Patients start with three drug chemotherapy (Regimen VAD; vincristine, dactinomycin and doxorubicin) and are evaluated and six and 12 weeks for feasibility of undergoing a partial nephrectomy/renal sparing surgery. At week 12 definitive surgery takes place followed by chemotherapy and radiation therapy based on histology and stage. Treatment continues for 25 or 31 weeks depending on histology. Patients are followed for up to 10 years following end of therapy.

ARM 2 (Unilateral High Risk tumors bilaterally predisposed): Patients start with either 2 drug or three drug chemotherapy (Regimen VA, VAD) and are evaluated a 6 and 12 weeks for feasibility of undergoing a partial nephrectomy. At week 12 definitive surgery takes place followed by chemotherapy.

ARM 3 (DHPLN): Patients with this rare disease are diagnosed based on cross-sectional imaging characteristics and undergo 2 drug chemotherapy (Regimen;VA). Patients are reassessed at 6 weeks and 12 weeks. If disease has responded or stayed stable chemotherapy is completed for 19 weeks (Regimen EE4A). If disease has progress a biopsy is performed to assess histology and adjust therapy based on the biopsy. This therapy may include, nephrectomy, chemotherapy or radiation therapy.

VAD REGIMEN: 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).

EE4A REGIMEN: 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).

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


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 249 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment for Patients With Bilateral, Multicentric, or Bilaterally-Predisposed Unilateral Wilms Tumor
Actual Study Start Date : July 13, 2009
Actual Primary Completion Date : December 31, 2016
Actual Study Completion Date : June 30, 2017


Arm Intervention/treatment
Experimental: Arm 1 (Bilateral Wilms Tumors)
Patients start with three drug chemotherapy (Regimen VAD; vincristine, dactinomycin and doxorubicin) and are evaluated and six and 12 weeks for feasibility of undergoing a partial nephrectomy/renal sparing surgery. At week 12 definitive surgery takes place followed by chemotherapy and radiation therapy based on histology and stage. Treatment continues for 25 or 31 weeks depending on histology. Patients are followed for up to 10 years following end of therapy.
Biological: Dactinomycin
Given IV
Other Names:
  • Actinomycin A IV
  • Actinomycin C1
  • ACTINOMYCIN D
  • Actinomycin I1
  • Actinomycin IV
  • Actinomycin X 1
  • Actinomycin-[thr-val-pro-sar-meval]
  • Cosmegen
  • DACT
  • Dactinomycine
  • Lyovac Cosmegen
  • Meractinomycin

Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
  • 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)
  • ADM
  • Adriacin
  • Adriamycin
  • Adriamycin Hydrochloride
  • Adriamycin PFS
  • Adriamycin RDF
  • ADRIAMYCIN, HYDROCHLORIDE
  • Adriamycine
  • Adriblastina
  • Adriblastine
  • Adrimedac
  • Chloridrato de Doxorrubicina
  • DOX
  • DOXO-CELL
  • Doxolem
  • Doxorubicin.HCl
  • Doxorubin
  • Farmiblastina
  • FI 106
  • FI-106
  • hydroxydaunorubicin
  • Rubex

Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • irradiation
  • Radiation
  • Radiotherapeutics
  • RADIOTHERAPY
  • RT
  • Therapy, Radiation

Procedure: Therapeutic Conventional Surgery
Undergo surgical resection

Drug: Vincristine Sulfate
Given IV
Other Names:
  • Kyocristine
  • Leurocristine sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate

Experimental: Arm 2 (Unilateral High Risk tumors bilaterally predisposed)
Patients start with either 2 drug or three drug chemotherapy (Regimen VA, VAD) and are evaluated a 6 and 12 weeks for feasibility of undergoing a partial nephrectomy. At week 12 definitive surgery takes place followed by chemotherapy.
Biological: Dactinomycin
Given IV
Other Names:
  • Actinomycin A IV
  • Actinomycin C1
  • ACTINOMYCIN D
  • Actinomycin I1
  • Actinomycin IV
  • Actinomycin X 1
  • Actinomycin-[thr-val-pro-sar-meval]
  • Cosmegen
  • DACT
  • Dactinomycine
  • Lyovac Cosmegen
  • Meractinomycin

Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
  • 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)
  • ADM
  • Adriacin
  • Adriamycin
  • Adriamycin Hydrochloride
  • Adriamycin PFS
  • Adriamycin RDF
  • ADRIAMYCIN, HYDROCHLORIDE
  • Adriamycine
  • Adriblastina
  • Adriblastine
  • Adrimedac
  • Chloridrato de Doxorrubicina
  • DOX
  • DOXO-CELL
  • Doxolem
  • Doxorubicin.HCl
  • Doxorubin
  • Farmiblastina
  • FI 106
  • FI-106
  • hydroxydaunorubicin
  • Rubex

Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • irradiation
  • Radiation
  • Radiotherapeutics
  • RADIOTHERAPY
  • RT
  • Therapy, Radiation

Procedure: Therapeutic Conventional Surgery
Undergo surgical resection

Drug: Vincristine Sulfate
Given IV
Other Names:
  • Kyocristine
  • Leurocristine sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate

Experimental: Arm 3 (DHPLN)
Patients with this rare disease are diagnosed based on cross-sectional imaging characteristics and undergo 2 drug chemotherapy (Regimen;VA). Patients are reassessed at 6 weeks and 12 weeks. If disease has responded or stayed stable chemotherapy is completed for 19 weeks (Regimen EE4A). If disease has progress a biopsy is performed to assess histology and adjust therapy based on the biopsy. This therapy may include, nephrectomy, chemotherapy or radiation therapy.
Biological: Dactinomycin
Given IV
Other Names:
  • Actinomycin A IV
  • Actinomycin C1
  • ACTINOMYCIN D
  • Actinomycin I1
  • Actinomycin IV
  • Actinomycin X 1
  • Actinomycin-[thr-val-pro-sar-meval]
  • Cosmegen
  • DACT
  • Dactinomycine
  • Lyovac Cosmegen
  • Meractinomycin

Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
  • 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)
  • ADM
  • Adriacin
  • Adriamycin
  • Adriamycin Hydrochloride
  • Adriamycin PFS
  • Adriamycin RDF
  • ADRIAMYCIN, HYDROCHLORIDE
  • Adriamycine
  • Adriblastina
  • Adriblastine
  • Adrimedac
  • Chloridrato de Doxorrubicina
  • DOX
  • DOXO-CELL
  • Doxolem
  • Doxorubicin.HCl
  • Doxorubin
  • Farmiblastina
  • FI 106
  • FI-106
  • hydroxydaunorubicin
  • Rubex

Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • irradiation
  • Radiation
  • Radiotherapeutics
  • RADIOTHERAPY
  • RT
  • Therapy, Radiation

Procedure: Therapeutic Conventional Surgery
Undergo surgical resection

Drug: Vincristine Sulfate
Given IV
Other Names:
  • Kyocristine
  • Leurocristine sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate




Primary Outcome Measures :
  1. Event-free survival [ Time Frame: Time from study enrollment to the first occurrence of progression, relapse after response or death from any cause, assessed up to 4 years ]
  2. Prevention of complete removal of at least one kidney in 50% of patients with bilateral Wilms tumor [ Time Frame: Up to 12 weeks ]
  3. 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 ]
  4. Facilitation of partial nephrectomy in lieu of total nephrectomy in 25% of patients with unilateral Wilms tumor [ Time Frame: Up to 12 weeks ]
  5. Percentage of patients with BWT undergoing definitive surgical treatment by week 12 [ Time Frame: 12 weeks ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   up to 29 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

      • 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
  • No concurrent aprepitant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00945009


  Show 169 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: Peter Ehrlich Children's Oncology Group

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00945009     History of Changes
Other Study ID Numbers: AREN0534
NCI-2011-01953 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000649716
AREN0534 ( Other Identifier: Childrens Oncology Group )
AREN0534 ( Other Identifier: CTEP )
U10CA180886 ( U.S. NIH Grant/Contract )
U10CA098543 ( U.S. NIH Grant/Contract )
First Posted: July 23, 2009    Key Record Dates
Last Update Posted: July 25, 2018
Last Verified: July 2018

Additional relevant MeSH terms:
Neoplasms
Wilms Tumor
Rhabdoid Tumor
Kidney Neoplasms
Hyperplasia
Beckwith-Wiedemann Syndrome
Neoplasms, Complex and Mixed
Neoplasms by Histologic Type
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplastic Syndromes, Hereditary
Kidney Diseases
Urologic Diseases
Genetic Diseases, Inborn
Pathologic Processes
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Doxorubicin
Liposomal doxorubicin
Dactinomycin
Vincristine
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic