A Study for Patients With Prostate Cancer to See Whether Delivering an Extra Dose of Radiation to Parts of the Body With More Cancer is Better Than Standard Treatment in Which the Same Dose of Radiation is Given Throughout the Prostate Gland

This is a prospective, open label, non-randomized, single site, phase I/II study of the safety and utility of 11C-Choline PET scans for delineation of intraprostatic lesions in subjects with localized intermediate risk prostate cancer and subsequent Enhanced EBRT (External Beam Radiation Therapy) to monitor toxicity, therapeutic response and recurrence.

The estimated total number of subjects required for protocol enrollment and baseline 11C-Choline PET scans is 63; however, the protocol will complete accrual only when 29 subjects have commenced Enhanced EBRT or the outlined stopping rules require a halt to accrual. Twenty-nine (29) subjects treated with Enhanced EBRT are required to assess the toxicity of this treatment based on the statistical analysis outlined in the protocol. Subjects will receive a fixed dose (400 MBq, 10%) of 11C-Choline and PET/CT imaging with co-registration 3T MRI imaging prior to Enhanced EBRT and two further doses of 11C-Choline at two intervals (3 and 6 months) thereafter.

Subjects with suitable intraprostatic lesion delineation with 11C-Choline will proceed to Enhanced EBRT, consisting of a dose prescription of 78 Gy in 25 fractions to the intraprostatic lesions and 68 Gy in 25 fractions (simultaneously) to the prostate gland. Subjects without suitable intraprostatic lesion delineation will be treated with Cross Cancer Institute standard of care EBRT and undergo follow-up for biochemical recurrence per protocol to determine the prognostic value of the baseline PET findings.

Subjects will be monitored for 11C-Choline safety and efficacy and for EBRT safety / toxicity and efficacy.

11C-Choline PET image intraprostatic lesion(s) will be analyzed by the relative uptake scores (RUS), tumor to background ratios (T/B) and SUVmax parameters. Adequate delineation will be determined by a lesion with tumor to background ration ≥2. This is defined in section 10.

11C-Choline PET image parameters will be correlated with other measures of progression and survival including biochemical disease free survival as indicators of Enhanced EBRT response.

Efficacy of 11C-Choline delineated Enhanced EBRT will be evaluated by progression and survival analysis compared to historical data from this population.

Safety of 11C-Choline will be determined by: vital signs, blood hematology and clinical biochemistry profile (pre-injection, post-imaging) and adverse event collection.

Safety/toxicity of 11C-Choline delineated Enhanced EBRT will be determined by adverse event collection, primarily for genitourinary and gastrointestinal toxicity and compared to historical data from this population.

Inclusion criteria

• Age ≥ 18 years
• Biopsy proven prostate cancer with an intermediate risk feature defined as

• Gleason score 7, PSA <20, T1-T2C or
• Gleason score 6, PSA 10-20, T1-T2C or
• Gleason Score 6 or 7, PSA <20, T2C
• Localized disease based on staging investigations including bone scan, CT abdomen and pelvis, and any other clinically indicated staging investigations
• Eligible for curative intent external beam radiotherapy
• Able and willing to follow instructions and comply with protocol
• Provide written informed consent prior to participation in the study
• Karnofsky Performance Scale Score 70-100

Exclusion criteria

• Have had a 11C-Choline PET scan performed within 4 weeks after any biopsies of the prostate (due to concern that acute post biopsy intraprostatic changes may affect scan accuracy)
• BMI ≥ 30
• The presence of a hip prosthesis
• Bilirubin ≥ 20 µmol/L
• AST or ALT ≥ 5 times the upper limits of normal
• Serious medical conditions which may prevent a patient from tolerating therapy such as: congestive heart failure, unstable angina, unstable ventricular arrhythmia, uncontrolled psychiatric conditions, serious infections and/or uncontrolled diabetes.
• Metastatic disease
• Prostate cancer with only low risk features or any high risk feature with a PSA ≥20 or T3 disease
• A history of previous carcinoma except for basal cell carcinoma
• Age < 18 years
• Prior treatment with hormonal therapy
• AUA prostate symptom score > 20
• Crohn's disease or ulcerative colitis
• Patient is unable to comply adequately iwth bowel or bladder prep during CT simulation