Proton beam radiation for treating Wilms tumor in children

Multi-Center Trial Sponsored by St. Jude Children's Research Hospital for the Treatment of Newly Diagnosed Patient's With Wilm's Tumor Requiring Abdominal Radiation Delivered With Proton Beam Irradiation

This study tests if proton beam radiation can safely treat Wilms tumor in children while protecting healthy tissues better than regular radiation.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 260 (estimated)
• Sex: All
• Sponsor: St. Jude Children's Research Hospital (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Memphis, Tennessee)
• Trial ID: NCT04968990 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of proton beam radiation therapy (PBRT) for children diagnosed with Wilms tumor, focusing on minimizing damage to surrounding healthy tissues while effectively targeting the tumor. Participants will receive PBRT based on their cancer stage and surgical findings, with specific protocols for those with varying degrees of tumor involvement. The study aims to assess the feasibility of sparing critical organs while maintaining effective treatment outcomes compared to traditional radiation methods.

Who should consider this trial

Good fit: Ideal candidates include children newly diagnosed with Wilms tumor who meet specific staging and surgical criteria.

Not a fit: Patients with unfavorable histology or those who have already received significant prior therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to improved treatment outcomes and reduced side effects for children with Wilms tumor.

How similar studies have performed: Other studies have shown promise with proton beam therapy in pediatric cancers, suggesting potential for success in this novel application.

Eligibility criteria

Inclusion Criteria:

* 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)
  * The tumor is not completely resectable because of local infiltration into vital structures
  * Tumor spillage occurring either before or during surgery
  * A trans abdominal biopsy (regardless of type- tru-cut, open or fine needle aspiration) was performed prior to resection or chemotherapy. Retroperitoneal biopsies DO NOT require radiotherapeutic management like stage III
  * Tumor is removed in greater than one piece (e.g. tumor cells are found in a separately excised adrenal gland; a tumor thrombus within the renal vein is removed separately from the nephrectomy specimen). Extension of the primary tumor within vena cava into thoracic vena cava and heart is considered Stage III, rather than Stage IV even though outside the abdomen.
* Stage IV - Hematogenous metastases (lung, liver, bone, brain, etc.), or lymph node metastases outside the abdomino-pelvic region are present. (The presence of tumor within the adrenal gland is not interpreted as metastasis and staging depends on all other staging parameters present). Patients with lung involvement and local abdominal stage I or II are eligible to remain on trial for whole lung irradiation objective.
* Stage V - Bilateral renal involvement by tumor is present at diagnosis. An attempt should be made to stage each side according to the above criteria on the basis of the extent of disease
* Patients that have or will receive neoadjuvant chemotherapy for unresected unilateral or bilateral Wilms tumor without a biopsy are not assumed to be require adjuvant radiation on this study. That determination will be based on surgical findings and the approach to treatment detailed in the protocol.

Timing

* Patients undergoing upfront surgery must start RT, if indicated, within 28 days of definitive surgery with a goal of starting RT by day 21.
* Patients receiving neoadjuvant chemotherapy will be enrolled either at diagnosis (if at St. Jude) or at the time of RT.

Other Criteria

• Female patients of childbearing potential (age ≥10 years old or post-menarche) must have a negative pregnancy test prior to enrollment.

Exclusion Criteria:

* 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.

Where this trial is running

Memphis, Tennessee

• St.Jude Children's Research Hospital — Memphis, Tennessee, United States (Recruiting)

Study contacts

• Principal investigator: Matthew J Krasin, MD — St. Jude Children's Research Hospital
• Study coordinator: Matthew J Krasin, MD

Conditions Wilms Tumor; Retroperitoneum; Retroperitoneal subsites; Kidney; Lymph node involvement; Abdomen