Treatment of Newly Diagnosed Patient's With Wilm's Tumor Requiring Abdominal Radiation Delivered With Proton Beam Irradiation

NCT04968990 | Recruiting Phase 2 FDA Device

• 1 other identifier: SJWT21
• Study Type: interventional
• Target: 260
• Locations: 1 country
• Sites: 1

Brief Summary

Participants are being asked to take part in this clinical trial, a type of research study, because the participants have a Wilms Tumor cancer. Primary Objectives To determine whether delivery of proton beam radiation to a conformal reduced target volume in the flank allows normal flank growth compared to the contralateral untreated side and non-irradiated patients. Secondary Objectives To deliver proton beam radiation to a conformal reduced target volume (partial kidney proton beam radiation therapy) in the affected kidney(s) for patients with Stage V (bilateral Wilms tumor) and specific involved surgical margins yielding no reduction in the high control rates seen with more traditional flank / whole kidney fields. Exploratory Objectives

• Study the feasibility of sparing the residual kidney, spine and liver in patients requiring whole abdomen radiation therapy using either a proton beam treatment technique or intensity-modulated radiation therapy ( IMRT) photon based technique.
• Study the feasibility of delivering whole lung radiation therapy with proton beams with the goals of sparing the developing breast tissue, heart structures, thyroid and liver.
• Develop simultaneous xenografts and organoid models from the same starting material to study Wilms tumor biology and compare responses to chemotherapeutic agents.
• Define the evolution of organ specific (kidney, liver, pancreas, etc.) abnormalities (laboratory studies) as an early marker of possible late end organ damage and their relationship to radiation.
• Study and evaluate impact of proton therapy on the musculoskeletal system and physical performance and compare with photon therapy cases treated with classical treatment fields.
• Assess CTC-AE and Pediatric Patient Reported Outcomes during radiation and in follow-up, correlating with disease, treatment and patient variables.
• Correlate quantitative MRI values, including apparent diffusion coefficient (ADC) values, with histopathology findings post-surgery in children with (bilateral) Wilms.
• Assess daily variations in proton range along each treatment beam using standard pre-treatment cone beam CT or on-treatment MR.

Conditions

Wilms Tumor

Keywords

Retroperitoneum; Retroperitoneal subsites; Kidney; Lymph node involvement; Abdomen

Outcome Measures

Primary Outcomes (4)

• Half circumference at 3 year

  Half circumference measurement at 3 year from irradiated and unirradiated hemi-abdomen for patients in need of flank radiation

  3 years after all patients finish proton therapy

• Half circumference at 5 year

  Half circumference measurement at 5 year from irradiated and unirradiated hemi-abdomen for patients in need of flank radiation

  5 years after all patients finish proton therapy

• Half circumference at 7 year

  Half circumference measurement at 7 year from irradiated and unirradiated hemi-abdomen for patients in need of flank radiation

  7 years after all patients finish proton therapy

• Half circumference at 10 year

  Half circumference measurement at 10 year from irradiated and unirradiated hemi-abdomen for patients in need of flank radiation

  Half circumference measurement at 10 year from irradiated and unirradiated hemi-abdomen

Secondary Outcomes (1)

• Local control rate in a partially radiated kidney

  5 years

Study Arms (3)

Favorable Histology Stage I & II and FH Stage III/IV

ACTIVE COMPARATOR

Favorable Histology Stage I \& II and FH Stage III/IV Delayed Local Control with clear surgical margins and pathologically negative lymph nodes. Participants will undergo complete surgical resection at diagnosis or after 6-12 weeks of induction chemotherapy.

Procedure: Complete Surgical Resection

Stage III & IV Adjuvant RT and Stage V

ACTIVE COMPARATOR

Participants will undergo surgical resection at diagnosis or after 6-12 weeks of induction chemotherapy. Those with evidence of LN involvement, surgical margin involvement, local or diffuse spill, gross disease in the renal bed or peritoneal implants, will receive adjuvant PBRT.

Device: Proton Beam Radiation (PBRT); Drug: DD-4A Chemotherapy Regimen; Procedure: Surgical Resection

Stage V Adjuvant RT:

ACTIVE COMPARATOR

Participants will undergo partial nephrectomy after 6-12 weeks of induction chemotherapy. Those with evidence of LN involvement, surgical margin involvement, local or diffuse spill, gross disease in the renal bed or peritoneal implants, will receive adjuvant PBRT

Device: Proton Beam Radiation (PBRT); Drug: DD-4A Chemotherapy Regimen; Procedure: Partial Nephrectomy

Interventions

Proton Beam Radiation (PBRT) DEVICE

The treatment approach with radiation therapy prescribed in this trial is designed to deliver highly conformal radiation therapy (proton beam radiation or intensity modulated photon radiation) to target volumes that are based on the burden of disease.

Stage III & IV Adjuvant RT and Stage V; Stage V Adjuvant RT:

DD-4A Chemotherapy Regimen DRUG

Patients will receive standard of care chemotherapy based on diagnosis and stage.

Stage III & IV Adjuvant RT and Stage V; Stage V Adjuvant RT:

Surgical Resection PROCEDURE

Participants will undergo surgical resection at diagnosis or after 6-12 weeks of induction chemotherapy.

Stage III & IV Adjuvant RT and Stage V

Complete Surgical Resection PROCEDURE

Participants will undergo complete surgical resection at diagnosis or after 6-12 weeks of induction chemotherapy

Favorable Histology Stage I & II and FH Stage III/IV

Partial Nephrectomy PROCEDURE

Participants will undergo partial nephrectomy after 6-12 weeks of induction chemotherapy.

Stage V Adjuvant RT:

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients are eligible to be enrolled on this trial at the time of initial (or presumptive) diagnosis of Wilms tumor, at the time of surgery or at the time of radiation treatment.
• Patients that are determined to be stage I or II will be eligible for the surgical and biologic aspects of this trial but will otherwise be followed per institutional standards and be "off therapy" at the time of stage determination (followed only for survival).
• Patients identified to have an anaplastic or other unfavorable tissue component (non-Wilms histology) to their tumor may have tissue assessed for the biology objective but will be removed from the therapeutic portion of the study at the time of identification of this pathologic finding.
• Performance Level • The Karnofsky performance status must be ≥50 for patients \>16 years of age and the Lansky performance status must be ≥ 50 for patients ≤ 16 years of age.
• Prior Therapy
• Only prior therapy with the initial chemotherapy regimen defined in section 5.1 and Appendix III are allowed for patients that are treated with neoadjuvant chemotherapy. These patients may change to an alternate regime based on response or biologic features and noted in section 5.1. Prior biopsy or surgery is allowed.
• Prior radiation therapy is not allowed if directed at the abdomen. Emergent RT to other sites of disease is acceptable.
• Organ Function Requirements:
• None - As per institutional standard of care. Diagnosis / Stage
• Presumed diagnosis of Wilms tumor (continued management on trial will depend on stage and histology)
• Resected upfront stage III, IV or V favorable histology Wilms tumor. Stage III includes any one or multiples of the following:
• Lymph nodes within the abdomen or pelvis are involved by tumor. (Lymph node involvement in the thorax, or other extra-abdominal sites is a criterion for Stage IV)
• The tumor has penetrated through the peritoneal surface
• Tumor implants are found on the peritoneal surface
• Gross or microscopic tumor remains post-operatively (e.g., tumor cells are found at the margin of surgical resection on microscopic examination - in the post chemotherapy setting only specific types of viable tumor at the surgical margin are considered stage III AND require adjuvant radiation - see surgery / pathology / radiation section for additional details)

You may not qualify if:

• Inability or unwillingness to provide written informed consent
• Prior radiation therapy to a site to be treated with proton / photon radiation as part of this trial. Emergent radiation is allowed.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (1)

St.Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

Related Links

• St.Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Wilms Tumor

Interventions

Proton Therapy

Condition Hierarchy (Ancestors)

Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Heavy Ion Radiotherapy; Radiotherapy; Therapeutics

Study Officials

• Matthew J Krasin, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matthew J Krasin, MD

CONTACT

888-226-4343; referralinfo@stjude.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2021
• First Posted: July 20, 2021
• Study Start: August 19, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2036
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available at the time of article publication.
• Access Criteria: Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.

Locations

US (1)