Combination Chemotherapy With or Without Radiation Therapy in Treating Young Patients With Newly Diagnosed Stage III or Stage IV Wilms' Tumor - Full Text View

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:	Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: No masking Primary Purpose: Treatment
Official Title:	Treatment of Newly Diagnosed Higher Risk Favorable Histology Wilms Tumors

Resource links provided by NLM:

MedlinePlus related topics: Wilms Tumor

Genetic and Rare Diseases Information Center resources: Wilms' Tumor Perlman Syndrome

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

Secondary Outcome Measures:

Event Free Survival Associated With the Burden of Pulmonary Metastatic Disease [ Time Frame: At 4 years ]
Probability of no relapse, secondary malignancy, or death after 4 year in the study.


Enrollment:	395
Study Start Date:	February 2007
Primary Completion Date:	October 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Stage IV and rapid complete response (RCR) of lung metastases Stage IV and rapid complete response (RCR) of lung metastases continuously treated with DD4A after 6 weeks of DD4A	Drug: doxorubicin hydrochloride Given IV Other Names: ADM ADR Adria Adriamycin PFS Adriamycin RDF Drug: liposomal vincristine sulfate Given IV Other Names: liposomal vincristine Marqibo vincristine liposomal vincristine sulfate liposome injection Procedure: conventional surgery Other Name: surgery, conventional Biological: dactinomycin Given IV Other Names: ACT-D actinomycin C1 AD Cosmegen DACT
Experimental: Stage IV and slow incomplete response (SIR) of lung metastases Stage IV and slow incomplete response (SIR) of lung metastases treated with Regimen M after 6 weeks of DD4A	Drug: doxorubicin hydrochloride Given IV Other Names: ADM ADR Adria Adriamycin PFS Adriamycin RDF Drug: liposomal vincristine sulfate Given IV Other Names: liposomal vincristine Marqibo vincristine liposomal vincristine sulfate liposome injection Procedure: conventional surgery Other Name: surgery, conventional Radiation: 3-dimensional conformal radiation therapy Other Names: 3D conformal radiation therapy 3D-CRT Biological: dactinomycin Given IV Other Names: ACT-D actinomycin C1 AD Cosmegen DACT Drug: cyclophosphamide Given IV Other Names: CPM CTX Cytoxan Endoxan Endoxana Drug: etoposide Given IV Other Names: EPEG VP-16 VP-16-213
Stage III/IV with LOH 1p and 16q treated with Regimen M Stage III/IV with LOH 1p and 16q treated with Regimen M	Drug: doxorubicin hydrochloride Given IV Other Names: ADM ADR Adria Adriamycin PFS Adriamycin RDF Drug: liposomal vincristine sulfate Given IV Other Names: liposomal vincristine Marqibo vincristine liposomal vincristine sulfate liposome injection Procedure: conventional surgery Other Name: surgery, conventional Radiation: 3-dimensional conformal radiation therapy Other Names: 3D conformal radiation therapy 3D-CRT Biological: dactinomycin Given IV Other Names: ACT-D actinomycin C1 AD Cosmegen DACT Drug: cyclophosphamide Given IV Other Names: CPM CTX Cytoxan Endoxan Endoxana Drug: etoposide Given IV Other Names: EPEG VP-16 VP-16-213
Stage IV with non-lung disease treated with Regimen M Stage IV with non-lung disease treated with Regimen M	Drug: doxorubicin hydrochloride Given IV Other Names: ADM ADR Adria Adriamycin PFS Adriamycin RDF Drug: liposomal vincristine sulfate Given IV Other Names: liposomal vincristine Marqibo vincristine liposomal vincristine sulfate liposome injection Procedure: conventional surgery Other Name: surgery, conventional Biological: dactinomycin Given IV Other Names: ACT-D actinomycin C1 AD Cosmegen DACT Drug: cyclophosphamide Given IV Other Names: CPM CTX Cytoxan Endoxan Endoxana Drug: etoposide Given IV Other Names: EPEG VP-16 VP-16-213
Stage IV with lung metastases Stage IV with lung metastases treated with DD4A for less than 6 weeks and/or response inevaluable at week 6	Drug: doxorubicin hydrochloride Given IV Other Names: ADM ADR Adria Adriamycin PFS Adriamycin RDF Drug: liposomal vincristine sulfate Given IV Other Names: liposomal vincristine Marqibo vincristine liposomal vincristine sulfate liposome injection Procedure: conventional surgery Other Name: surgery, conventional Biological: dactinomycin Given IV Other Names: ACT-D actinomycin C1 AD Cosmegen DACT

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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 (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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 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: NCT00379340

Show 207 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators


Principal Investigator:	David Dix, MD	Children's Oncology Group

More Information


Responsible Party:	Children's Oncology Group
ClinicalTrials.gov Identifier:	NCT00379340 History of Changes
Other Study ID Numbers:	AREN0533 NCI-2009-00419 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) CDR0000496508 ( Other Identifier: Clinical Trials.gov ) U10CA098543 ( US NIH Grant/Contract Award Number ) COG-AREN0533 ( Other Identifier: Children's Oncology Group )
Study First Received:	September 19, 2006
Results First Received:	December 6, 2016
Last Updated:	May 17, 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 Vincristine Etoposide Liposomal doxorubicin	Doxorubicin Cyclophosphamide Dactinomycin Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antibiotics, Antineoplastic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors

ClinicalTrials.gov processed this record on June 27, 2017