Ultra-hypofractionated Carbon-ion Therapy for Prostate Cancer

Carbon-ion Therapy With Ultra-hypofractionated RadiothErapy for Localized Prostate Cancer (CURE-PC-1): Phase I Clinical Trial

This is a single-arm, exploratory phase I clinical trial evaluating the safety and efficacy of ultra-hypofractionated carbon ion radiotherapy (CIRT) in 6 fractions compared to the conventional 12-fraction regimen in patients with low- and intermediate-risk localized prostate cancer. A total of 20 patients will be enrolled sequentially and treated with CIRT at 7 GyE per fraction, delivered twice weekly on alternating days, for a total of 6 fractions (total prescribed dose: 42 GyE). Androgen deprivation therapy for 6 months will be administered concurrently in patients classified as unfavorable intermediate-risk. The primary endpoint is the incidence of acute treatment-related toxicity of Grade 3 or higher per CTCAE v5.0 occurring within 90 days after completion of CIRT. Secondary endpoints include the incidence of late toxicity, biochemical relapse-free survival (bRFS), and quality of life assessed by EPIC-26 and IPSS questionnaires. Patients will undergo scheduled follow-up visits for 2 years after treatment completion, followed by long-term follow-up through electronic medical record review up to 5 years.

STUDY DESIGN This study is a prospective, single-arm clinical study designed to evaluate the safety of an ultra-hypofractionated carbon ion radiotherapy (CIRT) regimen in patients with localized prostate cancer. A total of 20 participants will be enrolled sequentially at a single institution. An initial cohort of 10 participants will be enrolled first. If fewer than 2 participants develop Grade ≥3 treatment-related acute toxicity within 90 days of completing CIRT, an additional 10 participants will be enrolled to reach the total sample size of 20. Participants will receive CIRT according to the following procedures.

1. Carbon Ion Radiotherapy : CIRT will be administered at 7 GyE per fraction, twice weekly on alternating days, for a total of 6 fractions over 3 weeks (total prescribed dose: 42 GyE). At the investigator's discretion, a simultaneous integrated boost (SIB) of 6 GyE × 6 fractions (total 36 GyE) may be prescribed to the seminal vesicle target. Treatment planning will be performed using RayStation with consideration of dose constraints for the rectum and bladder.
2. Androgen Deprivation Therapy (ADT) : ADT will not be administered to low-risk and favorable intermediate-risk patients. Unfavorable intermediate-risk patients will receive ADT concurrently for a total of 6 months, with the first dose completed prior to CIRT initiation. Permitted agents include GnRH agonists (Leuprolide, Goserelin, Triptorelin), GnRH antagonists (Degarelix, Relugolix), and anti-androgens (Bicalutamide, Flutamide, Nilutamide).
3. Permitted Procedures : Insertion of gold fiducial markers for image-guided radiotherapy and SpaceOAR hydrogel for rectal protection are permitted as part of the institutional standard of care and are not considered part of the study intervention.

Inclusion Criteria:

1. Male patients aged 19 years or older who are able to provide written informed consent

2. Histologically confirmed prostatic adenocarcinoma within 6 months prior to the first treatment (either carbon ion radiotherapy or androgen deprivation therapy, whichever comes first)

3. Documented pre-biopsy serum prostate-specific antigen (PSA) level available

4. Classified as one of the following risk groups based on NCCN Guidelines Version 5.2026:

   • Low risk: PSA ≤10 ng/mL AND Gleason score 6 (Grade Group 1) AND cT1-T2a
   • Intermediate risk: PSA 10-20 ng/mL OR Gleason score 7 (Grade Group 2-3) OR cT2b-T2c, without any high-risk features

5. No evidence of distant metastasis or regional lymph node metastasis

6. Adequate general condition for prostate cancer treatment as determined by ECOG Performance Status 0 or 1

7. Multiparametric prostate MRI performed prior to biopsy

Exclusion Criteria:

1. Prior history of pelvic radiotherapy or prostate surgery
2. History of malignancy other than prostate cancer, except for the following: cervical carcinoma in situ, completely resected non-melanoma skin cancer, or any cancer with disease-free status maintained for 5 or more years after treatment
3. Patients deemed inappropriate for carbon ion radiotherapy due to active infection, bleeding disorders, or severe cardiac, hepatic, or renal dysfunction, or patients who have undergone major surgery or experienced a major cardiovascular event (e.g., myocardial infarction, cerebral infarction, or cerebral hemorrhage) within the past 6 months
4. Patients with evidence of prostatitis or urinary tract infection on screening urinalysis and urine culture (However, enrollment is permitted if the condition improves on follow-up evaluation prior to carbon ion radiotherapy.)
5. Patients with psychiatric disorders or cognitive impairment considered unable to comply with the treatment plan
6. Patients currently participating in another investigational drug or medical device study concurrently with this study
7. Patients for whom carbon ion radiotherapy is physically difficult due to artificial hip prostheses or other metallic implants
8. Patients who underwent multiparametric prostate MRI after biopsy
9. Patients with a history of surgical treatment for benign prostatic hyperplasia, such as transurethral resection of the prostate (TURP) or holmium laser enucleation of the prostate (HoLEP)