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Trial registered on ANZCTR


Registration number
ACTRN12624001348549
Ethics application status
Approved
Date submitted
24/09/2024
Date registered
8/11/2024
Date last updated
8/11/2024
Date data sharing statement initially provided
8/11/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
To evaluate the feasibility of inserting Tutelix™ to reduce the dose of radiation to the rectum in men undergoing radiotherapy.
Scientific title
A Prospective, First-In-Human, Single Arm Study to Evaluate the SafeTy, Dosimetry, and Clinical Effects of a Perirectal Thermoresponsive Spacer Device in Patients Undergoing CuraTive Intent ProstatE Modulated Radiotherapy or Low Dose Rate (LDR) BrachytherApy (TUTELA)
Secondary ID [1] 313010 0
TUT-001A
Universal Trial Number (UTN)
Trial acronym
TUTELA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate cancer 335205 0
Condition category
Condition code
Cancer 331759 331759 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The Tutelix solution will be inserted transperineally under Transrectal Ultrasound (TRUS) guidance between the prostate and the rectum prior to radiotherapy.
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. This solution can be injected through a fine gauge needle and forms a cohesive hydrogel matrix upon administration. The gelation is triggered by physiological temperature and does not involve any polymerisation or chemical reaction.

The resulting hydrogel matrix is self-moulding as it sculpts with itself to form a consistent, homogenous and cohesive structure which can be viewed clearly under ultrasound imaging. This facilitates pinpoint visualization of the investigational device during its administration as it is molded into the optimal position.

The main component of the Tutelix investigational device is a proprietary polymer (PPHO). This polymer is the second generation of the PNPHO polymer, developed and clinically tested by Tetratherix Technology Pty Ltd for dental applications under (PET-A, HREC/16 SVHM 258, PET-B, HREC 043/19) and currently under investigation for dermal applications (TD-SI-001, HREC 288/23).
PNPHO and PPHO are both dissolved in buffered solutions, which are 95% similar in terms of chemical/ molar composition and have identical mode of action and thermoresponsive properties.

The clinical investigation involves 2 stages:
Cohort 1: An open-label and single-arm study of up to 15 participants (3 in the Stage 1 and the additional 12 participants after Safety Review Meeting (SRM )in Stage 2) pre-planned to receive Low-Dose-Rate (LDR) brachytherapy 145Gy with Iodine 125 permanent seeds aiming for V100 >90% (as per TG43 guidelines) as part of definitive Radiotherapy (RT) for prostate cancer.

Cohort 2: An open-label and single-arm study of up to 15 participants (all treated in Stage 2), pre-planned to receive 60Gy in 20 fractions as part of definitive RT for prostate cancer.

The Tutelix will be administered by a radiation oncologist or urologist with extensive experience in prostate rectal spacers. The injection of the Tutelix takes 1-2 minutes. The total procedure time is 15-20 minutes including preparation time.
8-10mls of the solution is administered, this is at the discretion of the proceduralist, given the different anatomical variations such as size of prostate and position of rectum as this varies.
Preclinical studies indicate the Tutelix hydrogel remains in the body for 6 months, this is a secondary endpoint of the study.
Review of medical records and procedural surveys will be used to monitor adherence to the intervention.

Stage 1 duration will be less than 3 months.
Stage 2 will commence after the safety review meeting for stage 1, which will be approximately 28 days after stage 1.
The duration of Stage 2 is 12 months.
Intervention code [1] 329553 0
Treatment: Devices
Intervention code [2] 329646 0
Treatment: Other
Comparator / control treatment
There is no control required by study design, as extensive literature is available on spacer products currently in use.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 339424 0
Assess the dose of radiation to the rectum after Tutelix™ insertion.
Assessment method [1] 339424 0
Cohort 1: Assess rectal volume receiving 100Gy (V100Gy) measured in cc Cohort 2: Assess rectal volume receiving 54Gy (V54Gy) measured in cc The data will be collected from the Radiotherapy treatment planning system and assessed, this is a commonly collected data point in radiation delivery.
Timepoint [1] 339424 0
For Cohort 1 this is Day 0 - this is the date of product insertion and brachytherapy insertion. For Cohort 2 this is Day 14 - radiotherapy begins at approximately day 14
Secondary outcome [1] 439923 0
Dosimetry Evaluation - COMPOSITE
Assessment method [1] 439923 0
Cohort 1: Assess highest radiation dose to 1cc (D1cc) and 2cc (D2cc) of rectum. Additionally, doses to other nearby organs at risk (OAR) will be extensively evaluated Cohort 2: Assess maximum rectal dose (d0.5cc), and volume of rectum receiving 40Gy (V40Gy). Additionally doses to other nearby organs at risk (OAR) will be extensively evaluated The data will be collected from the Radiotherapy treatment planning system and assessed,
Timepoint [1] 439923 0
Cohort 1 Day 0 is Tutelix Insertion and brachytherapy Cohort 1 Day 28 is 28 days post last brachytherapy Cohort 1 Day 90, Day 180, Day 365 is post Tutelix insertion and radiotherapy Cohort 2 Day 0 is Tutelix insertion Cohort 2 Day 28 is post last External Beam Radiation Therapy (ERBT) Cohort 2 Day 90, 180 and 365 is post Tutelix Insertion
Secondary outcome [2] 439924 0
Evaluate gastrointestinal toxicity according to CTCAE v5.0.
Assessment method [2] 439924 0
CTCAE v5.0- Common Terminology Criteria for Adverse Events (CTCAE v5.0) is a standardised system used to classify and grade the severity of adverse events (AEs) on the study and will include bladder, bowel and sexual function.
Timepoint [2] 439924 0
Day 1 of RT Day 28 post-LDR Brachytherapy (Cohort 1 only) Day 28 post-External Beam Radiation Therapy (EBRT) (Cohort 2 only) 3 months post-insertion 6 months post-insertion 12 months post- Tutelix™ insertion
Secondary outcome [3] 440305 0
Evaluate genitourinary toxicity according to CTCAE v5.0.
Assessment method [3] 440305 0
CTCAE v5.0- Common Terminology Criteria for Adverse Events (CTCAE v5.0) is a standardised system used to classify and grade the severity of adverse events (AEs) on the study and will include bladder, bowel and sexual function.
Timepoint [3] 440305 0
Day 1 of RT Day 28 post-LDR Brachytherapy (Cohort 1 only) Day 28 post-External Beam Radiation Therapy (EBRT) (Cohort 2 only) 3 months post-insertion 6 months post-insertion 12 months post- Tutelix™ insertion
Secondary outcome [4] 440306 0
Evaluate Sexual Toxicity according to CTCAE v5.0.
Assessment method [4] 440306 0
CTCAE v5.0- Common Terminology Criteria for Adverse Events (CTCAE v5.0) is a standardised system used to classify and grade the severity of adverse events (AEs) on the study and will include bladder, bowel and sexual function.
Timepoint [4] 440306 0
Day 1 of RT Day 28 post-LDR Brachytherapy (Cohort 1 only) Day 28 post-External Beam Radiation Therapy (EBRT) (Cohort 2 only) 3 months post-insertion 6 months post-insertion 12 months post- Tutelix™ insertion
Secondary outcome [5] 441176 0
Assess Bowel Quality Of Life
Assessment method [5] 441176 0
Quality of life will be assessed using the Expanded Prostate Cancer Index Composite questionnaire.
Timepoint [5] 441176 0
Day 1 of RT Day 28 post-LDR Brachytherapy (Cohort 1 only) Day 28 post-External Beam Radiation Therapy (EBRT) (Cohort 2 only) 3 months post-insertion 6 months post-insertion 12 months post- Tutelix™ insertion

Eligibility
Key inclusion criteria
Cohort 1:
1. Subject must sign an Informed Consent Form (ICF) indicating that he understands the purpose of, and procedures required for the study and is willing to participate for the entire duration.
2. Willing and able to complete all requested study follow up. Patients not suitable for MRI can still be registered on trial (and will not have day 28, 3, 6 and 12 month MRI)
3. Histologically proven low to intermediate risk prostate cancer (ISUP 1-3) suitable for LDR brachytherapy and Tutelix™ insertion as determined by radiation oncologist and proceduralist
4. Clinical stage T1c-­T2N0 or N0M0
5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2
6. Gleason score < /= 7
7. Fit for general, spinal or local anaesthetic
8. Life expectancy > 10 years
9. PSA < 20ng/mL

Cohort 2
1. Subject must sign an Informed Consent Form (ICF) indicating that he understands the purpose of, and procedures required for the study and is willing to participate for the entire duration.
2. Willing and able to complete all requested study follow up. Patients not suitable for MRI can still be registered on trial (and will not have baseline, 3month, 6 and 12 month MRI)
3. Histologically proven low to intermediate risk prostate cancer (ISUP 1-3) suitable for EBRT and Tutelix™ insertion as determined by radiation oncologist and proceduralist.
4. Clinical stage T1c-­T2N0M0
5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2
6. Gleason score < / =7
7. Fit for general, spinal or local anaesthetic
8. Life expectancy > 10 years
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Cohort 1:
1. Metastatic disease including regional nodal metastasis.
2. Patients requiring radiation to pelvis
3. Patients with poor urinary function (peak urinary flow rate <10 mL/sec or postvoid residual > 100 mL) have a higher risk of post-implant urinary obstruction and require urological assessment prior to considering implant
4. Obstruction resulting from a large median lobe or high bladder neck may be managed
5. Non-rheumatoid collagen vascular disorders
6. Inflammatory bowel disease and/or history of adhesions/bowel obstruction
7. Previous high dose RT to pelvis defined as any patient receiving more than 30Gy to below bottom of the 5th lumbar vertebrae (L5).
8. Extracapsular extension of prostate cancer
9. Prostate volume in relation to pubic arch interference
10. Large TURP defect which precludes seed placement and acceptable dosimetry
11. Estimated Prostate volume >80cm3
12. Androgen deprivation therapy unless started or investigator intends to start less than 45 days prior to Injection and will continue for a total planned duration of 3-6 months.
13. Allergy to anaesthetic or iodine.
14. Known rectal perforation or pre-existing prostatitis.
15. Ongoing inflammation or infection, in or near the intended treatment site.
16. Subjects with known iodine allergies

Cohort 2:
1. Any patient with high risk prostate cancer (T3a/b or T4, node positive)
2. Planned treatment to the pelvic region.
3. Metastatic disease including regional nodal metastasis
4. Patients requiring radiation to pelvis
5. Previous high dose radiation to the pelvis defined as any patient receiving more than 30Gy to below bottom of L5.
6. Poor urinary and bowel function.
7. Radio sensitising medications (e.g. methotrexate).
8. Inflammatory bowel disease and/or history of adhesions/bowel obstruction.
9. Bilateral hip replacement.
10. Cardiac implanted electronic device (CIED) unless radiation dose to CIED approved by treating cardiologist/electrophysiologist
11. Estimated prostate volume >80cm3
12. Androgen deprivation therapy unless started or investigator intends to start less than 45 days prior to Injection and will continue for a total planned duration of 3-6 months.
13. Allergy to anaesthetic.
14. Known rectal perforation or pre-existing prostatitis.
15. Ongoing inflammation or infection, in or near the intended treatment site.
16. Subjects with known iodine allergies

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
At least four analysis main datasets will be used for study data analyses:
Intention-to-Treat (ITT) Set - The Intention-To-Treat (ITT) analysis set for an open-label clinical trial refers to a principle used in the analysis of clinical trials where all participants who were initially allocated to Cohort 1 and 2 are included in the analysis, regardless of whether they completed the trial according to the study protocol or received the intended intervention. All baseline characteristics and disposition analyses will be conducted based on the ITT Set.

Safety Set Analysis (SAS) - The Safety Analysis Set will include all participants who underwent surgery and received any part of the Tutelix treatment or standard of care. The primary goal of the SAS is to assess and report on the safety and tolerability of the intervention.

Modified Intention-to-Treat (mITT) Analysis Set - The Modified Intention-To-Treat (mITT) Analysis Set is a variation of the traditional Intention-to-Treat (ITT) analysis and will include participants who underwent surgery and received any part of the Tutelix treatment or standard of care and participants who completed a specific initial assessment or baseline visit. Participants who enrolled but did not receive any treatment would be excluded from the mITT analysis

Per-Protocol (PP) Analysis Set- The Per-Protocol (PP) Analysis Set will include all participants in the mITT Set who do not have any major protocol deviations. Participants in this set will be analysed based on the treatment that they received.
Selected efficacy analyses will be conducted on the PP Analysis Set to support the main analysis.

All data will be summarised by treatment group and time point unless stated otherwise.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
25/11/2024
Actual
Date of last participant enrolment
Anticipated
1/07/2025
Actual
Date of last data collection
Anticipated
1/07/2026
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 27127 0
Icon Cancer Centre Richmond - Richmond
Recruitment hospital [2] 27128 0
Epworth Richmond - Richmond
Recruitment hospital [3] 27129 0
Icon Cancer Centre Gold Coast University Hospital - Southport
Recruitment postcode(s) [1] 43205 0
3121 - Richmond
Recruitment postcode(s) [2] 43206 0
4215 - Southport

Funding & Sponsors
Funding source category [1] 317449 0
Commercial sector/Industry
Name [1] 317449 0
Tutelix Pty Limited
Country [1] 317449 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Tutelix Pty Limited
Country
Australia
Secondary sponsor category [1] 319739 0
None
Name [1] 319739 0
Country [1] 319739 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316165 0
St Vincent's Hospital Melbourne Human Research Ethics Committee
Ethics committee address [1] 316165 0
Ethics committee country [1] 316165 0
Australia
Date submitted for ethics approval [1] 316165 0
12/09/2024
Approval date [1] 316165 0
23/09/2024
Ethics approval number [1] 316165 0

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 136998 0
Dr Matthew Neve
Address 136998 0
ICON Cancer Centre, Gold Coast University Hospital, Block C, Lower Ground, 1 Hospital Blvd, Southport, 4215, Queensland
Country 136998 0
Australia
Phone 136998 0
+61491189335
Email 136998 0
matthew.neve@icon.team
Contact person for public queries
Name 136999 0
Ruth Cremin
Address 136999 0
Tutelix Pty Limited, Unit 29 , 34-36 Ralph Street, Alexandria, NSW 2015
Country 136999 0
Australia
Phone 136999 0
+61 415686784
Email 136999 0
ruth.cremin@tutelix.com
Contact person for scientific queries
Name 137000 0
Andrew Beer
Address 137000 0
Tutelix Pty Limited, Unit 29 , 34-36 Ralph Street, Alexandria, NSW 2015
Country 137000 0
Australia
Phone 137000 0
+61 439094448
Email 137000 0
andrew.beer@tutelix.com

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.