Clinical trial NCT05302570: Neoadjuvant Short-course Hypofractionated PBT for Non-metastatic RPS
Official title: PROTONS-RPS: a Phase II Non-Randomized Open-label Single-arm Trial Of Neoadjuvant Short-course Hypofractionated Proton Beam Therapy for Non-metastatic RetroPeritoneal Sarcoma
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Retroperitoneal Sarcoma
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Robert L. Sloan Fund for Cancer Research
First posted: 2022-03-31
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The investigators' study titled "PROTONS-RPS: a Phase II non-Randomized Open-label single-arm Trial Of Neoadjuvant Short-course hypofractionated proton beam therapy for non-metastatic RetroPeritoneal Sarcoma" is a phase II trial evaluating the safety and efficacy of hypofractionated proton beam therapy (H-PBT) in the neoadjuvant (NA) setting for patients with non-metastatic retroperitoneal sarcoma (RPS) planned for surgical resection. This trial will include adult patients with resectable RPS.

Detailed description: The investigators' primary outcome is overall complication rate after treatment with NA H-PBT and surgical resection based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.2 Secondary objectives include evaluating the acute toxicity of H-PBT prior to surgical resection, rate of progression between diagnosis and definitive resection, early post-operative complication rate after resection of RPS in patients who received NA H-PBT, and local recurrence-free survival at 1 and 2 years. A priori subset analyses will be conducted for patients with well-differentiated and dedifferentiated liposarcoma.

The investigators plan to accrue a minimum of 44 patients to evaluate the investigators' primary outcome. Treatment will be 5 doses of H-PBT including a simultaneous integrated boost to at-risk margins followed by surgical resection after 4-6 weeks. Patients will be followed in the post-operative setting according to standard of care surveillance for RPS.

Eligibility criteria: Inclusion Criteria:

* Adult patients (≥18 years of age)
* Patients with primary non-recurrent retroperitoneal sarcoma
* Calculated creatinine clearance ≥50 mL/min and functional contralateral kidney based on nuclear medicine renal scan
* Normal bone marrow function (WBC ≥ 4 x109 /L)
* Eastern Cooperative Oncology Group status ≤ 2
* Cardiac function ≤ New York Heart Association class II
* Proton beam therapy approved by insurance (including Medicare/Medicaid)

Exclusion Criteria:

* Evidence of metastatic disease on staging CT of chest/abdomen/pelvis
* History of abdominal or pelvic radiation therapy
* Inability to tolerate supine position for duration of PBT simulation or treatment
* Tumor originating from gastrointestinal or gynecologic organs
* Specific sarcoma histologies including osteosarcoma, desmoid tumors, chondrosarcoma arising from vertebrae or pelvic bones, embryonal rhabdomyosarcoma
* Tumor extending into femoral or obturator canal
* History of systemic lupus erythematosus or ulcerative colitis
* Genetic syndrome with radiation-associated tumorigenicity (i.e.: Li-Fraumeni)
* Presence of clinically significant ascites
* Co-existing malignancy or treated malignancy in the last 2 years expected to limit life expectancy; does not include completely resected cutaneous basal cell carcinoma, squamous cell carcinoma, in situ breast or cervical malignancies, or other pathologies at the discretion of the investigators.

Primary outcomes:
measure: Overall serious adverse event rate for patients with primary resectable RPS receiving NA short-course h-PBT followed by surgical resection
timeFrame: 24 months
Secondary outcomes:
measure: Safety of NA short-course hypofractionated PBT for primary resectable RPS as assessed by incidence of acute Grade 3+ adverse events
timeFrame: Up to 6 weeks
measure: Tolerability of NA short-course hypofractionated PBT for primary resectable RPS as assessed by cessation of NA H-PBT due to toxicity or required dose reduction for serious adverse events
timeFrame: Up to 6 weeks
measure: Rate of local or distant tumor progression from diagnosis to time of surgery after treatment with PBT
timeFrame: Up to 6 weeks (pre-operatively)
measure: Rate of acute post-operative surgical complications in patients receiving NA short-course hypofractionated PBT
timeFrame: 30 days after surgery
measure: Local recurrence-free survival (LRFS)
timeFrame: Every 6 months, Up to 2 years
Other outcomes:
Locations:
city: Washington
country: United States
facility: Sibley Memorial Hospital
state: District of Columbia
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Amol Narang, MD
role: PRINCIPAL_INVESTIGATOR
References: