TUT-CIP-002: a Pivotal, Multicenter, Open-label, Randomized Controlled Trial to Evaluate the Effectiveness and Safety of Tutelix™ TL150 (IOP40), a Thermoresponsive Hydrogel Spacer for Prostate Radiotherapy

INTERVENTION: Tutelix™ is a water‐based solution of a proprietary synthetic polymer with rheological characteristics similar to water. It is radiologically opaque, ensuring safe, simple, and effective administration. Tutelix™ is intended to temporarily position the anterior rectal wall away from the prostate during radiotherapy for prostate cancer and, in creating this space, it is the intent to reduce the radiation dose delivered to the anterior rectum. The Tutelix™ injection will be performed transperineally by a credentialed proceduralist using a fine‐gauge needle, and the solution will polymerize into a cohesive gel within approximately 1 to 2 minutes upon contact with body temperature. A credential proceduralist is either a Urologist or Radiation Oncologist who is experienced in placement of fiducials and spacing devices and has been assessed and approved by the trial sponsor to complete this procedure. Approximately 15 to 20 mL of spacer material will be injected (exact volume per clinician discretion based on participant anatomy) to achieve a target separation of about 0.7 to 1.5 cm between the prostate capsule and anterior rectal wall. The procedure will take approximately 20‐30 minutes and will be completed under an anaesthetic. Approximately 7 days following the Inde Xprocedure, participants will commence standard of care Radiotherapy (RT) course which may include: External Beam Radiotherapy (EBRT) ‐ Conventional fractionation, e.g. 78‐82 Gy in 39‐42 fractions over 8 weeks OR Moderately hypofractionated RT, e.g. 60‐70 Gy in 20‐28 fractions over 4‐5 weeks. Stereotactic Body Radiotherapy (SBRT): 36 ‐ 40 Gy in 5 fractions over 1‐2 weeks. Tutelix™ will be predominantly resorbed within 12 months post‐insertion. CONDITION: Cancer ‐ Prostate Prostate Cancer; ; Prostate Cancer PRIMARY OUTCOME: To demonstrate any change to the radiation dose to the rectum by the insertion of the Tutelix™ spacer between the prostate and rectum.[Rectal volume receiving 90% of the prescription dose (Rectum V90%) measured in cc as assessed by the Radiotherapy treatment planning system. End of Radiotherapy course which is completed 2‐9 weeks following the index procedure (either insertion of fiducials or insertion of fiducials and Tutelix.] SECONDARY OUTCOME: Change from baseline in EPIC‐26 SF Quality of Life[EPIC‐26 SF HRQoL questionnaire scores. Baseline, end of treatment,3,6,12 (and 18 months if applicable).] Proportion of participants with Grade greater than or equal to 2 rectal toxicities following completion of radiotherapy.[Adverse events will be graded by NCI CTCAE, Version 5. ; Participants will be assessed by study clinicians at the scheduled follow‐up visit and rectal adverse events will be recorded and assigned a CTCAE grade. This will be assessed from the time of insertion of fiducials or fiducials and Tuteli Xat the end of radiation treatment, 3 months, 6 months, 12 months and 18 months after the insertion. ] The maximum gap distance (mm) between the posterior surface of the prostate and the anterior rectal wall following Tutelix™ placement, assessed on imaging during the radiotherapy course. ; ; [CT simulation and/or scheduled verification CT during radiotherapy (per protocol imaging schedule) via measurement of the posterior margin of the prostate and the closest anterior rectal wall surface. ; End of Radiotherapy course which is completed 2‐9 weeks following the inde Xprocedure (either insertion of fiducials or insertion of fiducials and Tutelix)] The mean gap distance (mm) between the posterior surface of the prostate and the anterior rectal wall following Tutelix™ placement, assessed on imaging during the radiotherapy course.[CT simulation and/or scheduled verification CT during radiotherapy (per protocol imaging schedule) via measurement of the posterior margin of the prostate and the closest anterior rectal wall surface. End of Radiotherapy course which is completed 2‐9 weeks following the inde Xprocedure (either insertion of fiducials or insertion of fiducials and Tutelix)] To assess doses of radiation received by comparing the CTV and PTV the bladder in participants with and without insertion of the Tutelix™ spacer. The CTV and PTV of the bladder will be assessed as a composite outcome.[Dosimetry to record difference in coverage of the bladder of CTV and PTV between RT planning #1 and RT planning #2. Treatment planning systems (TPS) are used in departments and have undergone rigorous verification. The software is able to capture this data easily and routinely. This is standard practice and dose not require additional confirmation as it is a mandatory requirement of all radiation oncology sites within Australia. Sites undergo routine quality assurance to ensure calibration of machines and dosimetry. End of Radiotherapy course which is completed 2‐9 weeks following the inde Xprocedure (either insertion of fiducials or insertion of fiducials and Tutelix)] To assess doses of radiation received by comparing the CTV and PTV the penile bulb in participants with and without insertion of the Tutelix™ spacer. The CTV and PTV of the penile bulb will be assessed as a composite outcome.[Dosimetry to record difference in coverage of the penile bulb of CTV and PTV between RT planning #1 and RT planning #2. Treatment planning systems (TPS) are used in departments and have undergone rigorous verification. The software is able to capture this data easily and routinely. This is standard practice and dose not require additional confirmation as it is a mandatory requirement of all radiation oncology sites within Australia. Sites undergo routine quality assurance to ensure calibration of machines and dosimetry. End of Radiotherapy course which is completed 2‐9 weeks following the inde Xprocedure (either insertion of fiducials or insertion of fiducials and Tutelix)] To assess doses of radiation received by the Clinical target volume (CTV) and Planning target volume (PTV) of the rectum in participants with and without insertion of the Tutelix™ spacer by assessment of the difference in coverage of CTV and PTV between RT planning #1 (planning before the inde Xprocedure) and RT planning #2 (planning after the inde Xprocedure) for the interventional group. The CTV and PTV of the rectum will be assessed as a composite outcome.[Dosimetry Evaluation: ; Record difference in coverage of CTV and PTV between RT planning #1 and RT planning #2; ; Maximum rectal dose (d0.5cc); ; Volume of rectum receiving 70% of prescription dose (Rectum V70%); ; Doses to other nearby organs at risk (OAR). ; Treatment planning systems (TPS) are used in departments and have undergone rigorous verification. The software is able to capture this data easily and routinely. This is standard practice and dose not require additional confirmation as it is a mandatory requirement of all radiation oncology sites within Australia. Sites undergo routine quality assurance to ensure calibration of machines and dosimetry. End of Radiotherapy course which is completed 2‐9 weeks following the inde Xprocedure (either insertion of fiducials or insertion of fiducials and Tutelix)] Tutelix™ volume following insertion [Visibility of prostate via Transrectal Ultrasound (TRUS) during injection of hydrogel and Volume measurements on MRI End of Inde Xprocedure] INCLUSION CRITERIA: Histologically confirmed adenocarcinoma of the prostate who is a candidate for external beam RT (including intensity‐modulated or image‐guided RT) and Tutelix™ insertion, as determined by radiation oncologist and proceduralist. Meets one of the following disease risk categories if they are planned for definitive treatment of the primary tumor (e.g. as part of a multimodal therapy approach): a. Localised prostate cancer: N0, M0; b. Low‐volume mCSPC, e.g. less than or equal to 4 bone metastases with none outside the vertebral column or pelvis, and no visceral metastasis. Participants must have an intact prostate (no prior prostatectomy) and baseline MRI demonstrating a clean tissue plane between prostate and rectum (no tumor invasion of rectal wall). Eastern Cooperative Oncology Group (ECOG) Performance Status of 0‐2 at Screening. Life expectancy greater than 5 years. In the opinion of the proceduralist, the participant must be fit for anes