Vincristine, Dactinomycin, and Doxorubicin With or Without Radiation Therapy or Observation Only in Treating Younger Patients Who Are Undergoing Surgery for Newly Diagnosed Stage I, Stage II, or Stage III Wilms' Tumor - Full Text View

Purpose

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.

Condition	Intervention	Phase
Stage I Wilms Tumor Stage II Wilms Tumor Stage III Wilms Tumor	Procedure: therapeutic conventional surgery Drug: vincristine sulfate Biological: dactinomycin Drug: doxorubicin hydrochloride Radiation: 3-dimensional conformal radiation therapy	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment
Official Title:	Treatment for Very Low and Standard Risk Favorable Histology Wilms Tumor

Resource links provided by NLM:

MedlinePlus related topics: Wilms Tumor

Drug Information available for: Dactinomycin Doxorubicin

Genetic and Rare Diseases Information Center resources: Wilms' Tumor

U.S. FDA Resources

Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:

Event Free Survival Probability [ Time Frame: 4 years ]
Probability of no relapse, secondary malignancy, or death after 4 year in the study.
Overall Survival (OS) Probability [ Time Frame: 4 years ]
Probability of being alive after 4 years in the study.

Secondary Outcome Measures:

Incidence of Contralateral Kidney Lesions [ Time Frame: During follow-up ]
Number of contralateral kidney lesions during follow-up.
Incidence of Renal Failure [ Time Frame: During follow-up ]
Number of renal failures defined as requiring dialysis or renal transplant as determined by low GFR during follow-up


Enrollment:	808
Study Start Date:	October 2006
Study Completion Date:	September 2015
Primary Completion Date:	December 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Nephrectomy and re-evaluation (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.	Procedure: therapeutic conventional surgery Undergo surgery Drug: vincristine sulfate Given IV Other Names: leurocristine sulfate VCR Vincasar PFS Biological: dactinomycin Given IV Other Names: ACT-D actinomycin C1 AD Cosmegen DACT Drug: doxorubicin hydrochloride Given IV Other Names: ADM ADR Adria Adriamycin PFS Adriamycin RDF Radiation: 3-dimensional conformal radiation therapy Patients undergo radiotherapy Other Names: 3D conformal radiation therapy 3D-CRT
Experimental: Nephrectomy, chemotherapy (standard-risk, stg I or II) 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.	Procedure: therapeutic conventional surgery Undergo surgery Drug: vincristine sulfate Given IV Other Names: leurocristine sulfate VCR Vincasar PFS Biological: dactinomycin Given IV Other Names: ACT-D actinomycin C1 AD Cosmegen DACT Drug: doxorubicin hydrochloride Given IV Other Names: ADM ADR Adria Adriamycin PFS Adriamycin RDF Radiation: 3-dimensional conformal radiation therapy Patients undergo radiotherapy Other Names: 3D conformal radiation therapy 3D-CRT
Experimental: Nephrectomy/biopsy, chemotherapy (standard-risk, stage III) 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.	Procedure: therapeutic conventional surgery Undergo surgery Drug: vincristine sulfate Given IV Other Names: leurocristine sulfate VCR Vincasar PFS Biological: dactinomycin Given IV Other Names: ACT-D actinomycin C1 AD Cosmegen DACT Drug: doxorubicin hydrochloride Given IV Other Names: ADM ADR Adria Adriamycin PFS Adriamycin RDF Radiation: 3-dimensional conformal radiation therapy Patients undergo radiotherapy Other Names: 3D conformal radiation therapy 3D-CRT

Detailed Description:

PRIMARY OBJECTIVES:

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).

SECONDARY OBJECTIVES:

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.

Eligibility


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

Criteria

Inclusion Criteria:

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:
    - Aniridia
    - 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

Contacts and Locations

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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00352534

Show 221 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Conrad Fernandez, MD	Children's Oncology Group

More Information


Responsible Party:	Children's Oncology Group
ClinicalTrials.gov Identifier:	NCT00352534 History of Changes
Other Study ID Numbers:	AREN0532 NCI-2009-01067 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) CDR0000487540 ( Other Identifier: ClinicalTrials.gov ) AREN0532 ( Other Identifier: Children's Oncology Group ) AREN0532 ( Other Identifier: CTEP ) U10CA098543 ( U.S. NIH Grant/Contract )
Study First Received:	July 13, 2006
Results First Received:	October 26, 2016
Last Updated:	April 5, 2017

Additional relevant MeSH terms:


Neoplasms Wilms Tumor Neoplasms, Complex and Mixed Neoplasms by Histologic Type Kidney Neoplasms Urologic Neoplasms Urogenital Neoplasms Neoplasms by Site Neoplastic Syndromes, Hereditary Kidney Diseases Urologic Diseases Genetic Diseases, Inborn Doxorubicin Liposomal doxorubicin Dactinomycin	Vincristine Antibiotics, Antineoplastic Antineoplastic Agents Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Phytogenic Tubulin Modulators Antimitotic Agents Mitosis Modulators Anti-Bacterial Agents Anti-Infective Agents Protein Synthesis Inhibitors Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on September 21, 2017