Efficacy and Tolerability of Rectal Budesonide Suppositories for Acute Radiation Proctitis in Male Patients with Prostate Carcinoma: A Phase II Randomized Controlled Trial

The primary objective is to evaluate the efficacy of once-daily 4 mg budesonide suppositories compared to placebo in improving Common Terminology Criteria for Adverse Events (CTCAE) grading for acute radiation proctitis in male patients with prostate carcinoma. Scope: 3, 5.

Secondary objectives include:

• Further assessment of CTCAE grading for proctitis.
• Evaluation of CTCAE grading for the lower gastrointestinal composite.
• Measurement of patient-reported symptom severity and symptomatic manifestation.
• Assessment of bowel-related function, general treatment response, and quality of life.
• Evaluation of tolerability.

This clinical trial involves 80 male participants aged 18 years or older. The study population consists of individuals diagnosed with prostate carcinoma, including cases of primary disease or biochemical recurrence. Participants must present with acute radiation proctitis symptoms, specifically characterized by a CTCAE grading for proctitis and diarrhea of grade 1 or higher for a minimum of three days. Eligible subjects are required to have undergone or be planned for external beam radiation therapy with a total dose of 60-80 Gy. Inclusion is further contingent upon an Eastern Cooperative Oncology Group performance status of ≤2 or a Karnofsky performance status of 70% or greater. Additionally, participants must demonstrate sufficient compliance with electronic patient-reported outcomes during the screening period.

This phase II, double-blind, randomized, placebo-controlled, two-arm parallel group clinical trial is designed to evaluate the efficacy and tolerability of budesonide 4 mg suppositories administered via rectal use once daily compared to a placebo for the amelioration of symptoms associated with acute radiation proctitis. The study involves male patients aged 18 years or older diagnosed with prostate carcinoma who exhibit CTCAE grading for proctitis and diarrhea of grade 1 or higher for at least three days. The research methodology includes a screening period to assess eligibility and electronic patient-reported outcomes compliance. Following screening, participants undergo an 8-week treatment period. The clinical sequence involves several scheduled visits, including a baseline assessment, follow-up visits at Visit 2 and Visit 4 to evaluate symptom reduction and therapeutic success, and a final assessment at Visit 5. Primary efficacy is measured by the time to the first improvement in proctitis grading. Secondary endpoints include assessments of rectal pain, diarrhea, fecal incontinence, and various gastrointestinal scores. The overall duration of participant involvement is determined by the 8-week treatment course and subsequent follow-up evaluations.

The experimental treatment consists of budesonide administered in the form of a 4 mg suppository. This medication is intended for rectal use once daily for a duration of 8 weeks to evaluate its efficacy in ameliorating symptoms of acute radiation proctitis.

The comparator treatment is a placebo administered via the same route and frequency as the active substance. This placebo-controlled study utilizes a double-blind design to compare the effects of the active medication against the non-active substance.

The primary efficacy endpoint is the time to the first improvement in CTCAE grading for acute radiation proctitis, defined as the number of days from baseline to the first occurrence of a lower grade sustained for at least three consecutive days. Secondary endpoints include the percentage of participants achieving a reduction in CTCAE grading for proctitis, diarrhea, rectal pain, and other components of the lower GI composite, including fecal incontinence, lower GI hemorrhage, and gastrointestinal pain, by one or two score points from baseline at Visit 2 and Visit 4. Additional assessments involve the time to first improvement for these lower GI symptoms.

Further evaluation of efficacy includes the following parameters measured at specific intervals:

• Course and change from baseline in the SHS-GI sum score and sub-scores at Visits 2, 4, and 5.
• Course and change from baseline in the PGI-S at Visits 2, 4, and 5.
• PGI-C assessments at Visits 2 and 4.
• Course and change from baseline in the EPIC Bowel Domain Score at Visits 2, 4, and 5.
• Therapeutic success and therapeutic benefit at Visit 4, determined by the PGA.
• Percentage of participants remaining symptom-free for at least ten consecutive days at Visit 4.
• Frequency and duration of rescue medication use at Visit 4.
• Investigator and participant efficacy assessments at Visit 4.

Clinical outcomes during the treatment period are also monitored, including average daily bowel movement frequency, the presence of bloody stool or mucous stool, and the intensity of pain during bowel movements. The assessment further includes the percentage of days with uncontrolled bowel movements, the use of pads, the impact of symptoms on daily life and functioning, and the necessity of medical intervention due to symptoms.