PHASE II RANDOMIZED TRIAL OF 2- VS 5-FRACTION PROSTATE STEREOTACTIC ABLATIVE RADIOTHERAPY
Trial ID: NCT06835725
Status: RECRUITING
Study type: INTERVENTIONAL
Phase: PHASE2
Start date: 2025-09-04
Completion date: 2033-04-30
Sponsor: British Columbia Cancer Agency
Conditions: Prostate CA
Interventions: Stereotactic Body Radiation Therapy (SBRT)
Locations: BC Cancer Radiation Oncology
Countries: Canada
Enrollment: 100
Age range: 18 Years - None
Sex: MALE

Summary:
Prostate cancer is a common cancer, and a significant cause of cancer death in men. There are many potentially curative treatment options for prostate cancers that have not spread. A relatively recent option is called prostate stereotactic ablative radiotherapy (SABR). SABR is a form of external beam radiotherapy, where patients receive a small number (5-7) of treatments (also called fractions) of radiation delivered in a highly accurate and precise fashion. Standard prostate SABR is generally given in 5 fractions and has been shown to be at least as effective as conventional external beam radiotherapy. Disease control with SABR appears excellent, and it compares favorably to surgery in terms of side effects and quality of life.

In theory, reducing the number of fractions from 5 to 2 may improve disease control and reduce side effects, in addition to providing added convenience for patients. Small studies suggest prostate SABR in 2 fractions may be highly effective and well tolerated. However, there is little available data comparing 2 and 5 fraction SABR head to head to tell us which is superior.

Two fraction SABR involves delivery of 2 large dose fractions of radiotherapy which could result in significant side effects if proper precautions are not taken. The use of continuous tracking of the prostate gland position during treatment delivery reduces the risk of missing the prostate or overdosing organs near by. Such tracking has been shown to reduce bladder side effects. Also, the use of a rectal spacer placed between the prostate and rectum has been shown to reduce bowel side effects. Also, advanced artificial intelligence (AI)-directed computer applications could potentially improve the targeting of radiation during each treatment.

The ADAPT-2 study is a randomized phase II trial comparing standard 5-fraction SABR with an experimental 2-fraction approach in men with intermediate risk prostate cancer. All treatment, whether 5 or 2-fractions, will use continuous prostate tracking (also called triggered imaging) and a rectal spacer (called Space OAR Hydrogel) to minimize side effects. The trial will also evaluate the potential of a new AI-guided dose guidance application to see if it can improve current methods of targeting SABR each day. This aspect of the study will be offline; that is, the AI application will not be used to actually target treatment for the trial patients. Rather, daily targeting of SABR will use standard conventional means, and the AI application will be studied in a simulated fashion to determine it is useful and can be incorporated into workflow.

The main goal of the ADAPT-25 study is to compare the long-term side effects and quality of life between 5- and 2-fraction prostate SABR. Secondary goals will be to compare the long-term disease control between 5-and 2-fraction prostate SABR, and to evaluate whether a novel AI-directed dose guidance application can be used to better target SABR by reducing doses to neighboring organs, and whether it can be easily fit into prostate SABR workflow.

Eligibility criteria:
Inclusion Criteria:

* • Age 18 or older.

  * Able to provide informed consent.
  * ECOG performance status 0 - 2.
  * Fit for all protocol treatment and follow-up.
  * Life Expectancy \> 5 years.
  * Histologically confirmed adenocarcinoma of the prostate, NCCN low or intermediate risk, with biopsy performed within the last 18 months:

Low risk = cT1-T2a,Gleason ≤ 6, and PSA \< 10ng/mL. Intermediate risk = at least one of: cT2b/T2c, PSA 10-20ng/mL, or Gleason 7, but not high risk.

* 6 months of Androgen Deprivation Therapy (ADT) is permitted for those with NCCN unfavorable intermediate risk disease (aka high-tier intermediate risk disease), defined as intermediate risk disease with one or more of: two or three intermediate risk features, Gleason 4+3, or ≥50% biopsy cores positive.
* For those with NCCN unfavorable intermediate risk disease, it is permitted for ADT to have been initiated prior to study enrollment provided it is possible for radiotherapy to be completed before completion of 6 months of ADT.
* Prostate volume \<100cc based on imaging or digital rectal examination.
* PSA within 90 days prior to registration. If ADT is started before registration, then the PSA must have been done no more than 90 day prior to the date of the first ADT injection.
* CT abdomen and pelvis within the 6 months prior to registration (may be omitted for NCCN low risk participants). If particpant started on ADT prior to registration, CT should be done before first ADT injection.
* Bone scan within the 6 months prior to of registration (may be omitted for NCCN low risk participants). If particpant started on ADT prior to registration, bone scan should be done before first ADT injection.
* Must be appropriate for and willing to undergo implantation of prostate fiducial markers and Space OAR Hydrogel.

Exclusion Criteria:

Clinical stage cT3 or greater. Gleason score 8 or greater. PSA \> 20ng/mL or greater. NCCN high or very high risk. Pelvic nodal metastases. Distant metastases. Previous malignancy within the last 5 years except basal or squamous cell carcinomas of the skin.

Previous pelvic radiotherapy. Any prior active local treatment for prostate cancer. Participants previously on active surveillance are eligible if they continue to meet all other eligibility criteria.

Unilateral or Bilateral hip prostheses. Medical conditions likely to make radiotherapy inadvisable (e.g., inflammatory bowel disease).

Medical condition that would make implantation of fiducial markers or hydrogel rectal spacer unsafe, in the opinion of the treating physician (e.g., pelvic or prostate abscess).

Medical condition or implant that prohibits MRI (e.g. pacemaker) Trans-urethral resection of the prostate (TURP), GreenLight Laser or Holmium Laser Prostate procedure within 6 months of radiotherapy.

Outcomes:
Freedom from grade 2 or higher toxicity