Clinical trial NCT06235697: Androgen Suppression Combined With Nodal Irradiation and Dose Escalated Prostate Treatment
Official title: Androgen Suppression Combined With Elective Nodal Irradiation and Dose Escalated Prostate Treatment: A Non-Inferiority, Phase III Randomized Controlled Trial of Stereotactic Body Radiation Therapy Versus Brachytherapy Boost in Patients With Unfavourable Risk Localized Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Prostate Cancer
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: NRG Oncology
First posted: 2024-02-01
Enrollment: 710
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is being done to answer the following question: Is the strategy to give higher doses of radiotherapy treatment over a shorter period of time using special equipment and fewer treatments (also known as Stereotactic Body Radiation Therapy or SBRT) as effective as usual external radiation therapy given with a brachytherapy boost (which involves radiation sources inserted directly into the prostate)?

Detailed description: The usual approach for patients with unfavourable prostate cancer who are not in a study is treatment with external beam radiation therapy (EBRT) to the pelvis and prostate in combination with hormone therapy (androgen deprivation therapy - ADT). To improve control of prostate cancer at risk of returning, additional treatment with a brachytherapy boost (insertion of radiation sources directly into the prostate) is recommended. For patients who get the usual approach for this cancer, about 89 out of 100 are free of cancer after 5 years.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed adenocarcinoma of the prostate diagnosed within the last 9 months
* Participants with unfavourable risk prostate cancer are eligible according to the following NCCN classification guidelines (Version 4.2022 - May 10, 2022):

  • Unfavourable-intermediate risk - has one or more of the following:
* 2 or 3 Intermediate Risk Factors (IRFs): cT2b-cT2c, Gleason 7 (grade group 2 or 3), and/or PSA 10-20 ng/ml;
* Gleason 4+3 (grade group 3)
* \> 50% biopsy cores positive

  • High risk - has one of the following:
* cT3a
* Gleason 8-10 (grade group 4 or 5)
* PSA \> 20 ng/ml

  • Very-high risk - has at least one of the following:
* cT3b-cT4
* Primary Gleason pattern 5
* 2 or 3 high risk features: cT3a, Gleason 8-10 (grade group 4 or 5), and/or PSA \> 20 ng/ml
* \> 4 cores with Gleason 8-10 (grade group 4 or 5)
* ECOG performance status of 0, 1 or 2
* Participants must be ≥ 18 years of age
* Judged to be medically fit for brachytherapy
* Participant is able (i.e. sufficiently fluent) and willing to complete the quality of life and/or health utility questionnaires in either English, French or Spanish
* Participants consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each participant must sign a consent form prior to enrollment in the trial to document their willingness to participate
* Participants must be accessible for treatment and follow-up. Investigators must assure themselves the participants enrolled on this trial will be available for complete documentation of the treatment, adverse events, and follow-up
* In accordance with CCTG policy, protocol treatment is to begin within 12 weeks of participant enrollment
* Participants must be willing to take precautions to prevent pregnancy while on study
* ADT (LHRH agonists, antagonists, or anti-androgens) for prostate cancer is permitted for up to 30 days before study enrollment
* 5-alpha reductase inhibitors (5-ARI) are allowed, but baseline PSA will be corrected if 5-ARI use occurs within 6 months of enrollment
* Participants may NOT have received other therapies including chemotherapy, PARPi, radioligand or other investigational drugs for prostate cancer
* Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Urinary function defined as International Prostate Symptom Score (IPSS) \< 20. Alpha blockers are allowed to treat baseline urinary function
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

Exclusion Criteria:

* Prior pelvic radiotherapy
* Contraindication to radical prostate radiotherapy (e.g. connective tissue disease or inflammatory bowel disease)
* Anticoagulation medication (if unsafe to discontinue for gold seed insertion or brachytherapy implant) and/or prior or current bleeding diathesis
* Prior steam vaporization (Rezum), transurethral resection of the prostate (TURP), prostatectomy (simple or radical), or any ablative therapy to the prostate (cryotherapy, HIFU, TULSA, focal laser ablation, photodynamic therapy)
* Prostate volume \> 60cc before start of androgen deprivation therapy
* Anatomy that would preclude precise brachytherapy implant (such as arch interference or large median lobe)
* Evidence of castrate resistance (defined as a rising PSA \> 3.0 ng/ml while testosterone is \< 3.0 nmol/l)
* Hip prosthesis

Primary outcomes:
measure: To compare the progression-free survival (PFS) of SBRT versus conventional EBRT plus brachytherapy boost defined as time to biochemical failure, initiation of salvage therapy, local-regional recurrence, distant progression, or death
timeFrame: 8.6 years
Secondary outcomes:
measure: Safety and tolerability assessed by CTCAE v5.0
timeFrame: 8.6 years
measure: PSA response at 4 years compared using a Cochran-Mantel-Haenszel (CMH) test
timeFrame: 8.6 years
measure: Metastasis-free Survival compared using the Gray's test
timeFrame: 8.6 years
measure: Cause-specific Survival compared using the Gray's test
timeFrame: 8.6 years
measure: Overall Survival analysed using a Cox proportional hazards model and graphically described using the Kaplan-Meier method
timeFrame: 8.6 years
measure: Participant-reported outcomes using EPIC-26 questionnaire
timeFrame: 8.6 years
measure: Participant-reported tolerability using PRO-CTCAE questionnaire
timeFrame: 8.6 years
measure: Economic Outcomes using EQ-5D-5L
timeFrame: 8.6 years
measure: Economic Outcomes using FACIT-COST
timeFrame: 8.6 years
Other outcomes:
Locations:
city: Creve Coeur
country: United States
facility: Siteman Cancer Center at West County Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center-South County
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Christian Hospital
state: Missouri
city: Saint Peters
country: United States
facility: Siteman Cancer Center at Saint Peters Hospital
state: Missouri
city: Midlothian
country: United States
facility: Bon Secours Saint Francis Medical Center
state: Virginia
city: Richmond
country: United States
facility: Bon Secours Cancer Institute at Reynolds Crossing
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University/Massey Cancer Center
state: Virginia
city: Mississauga
country: Canada
facility: Trillium Health Partners - Credit Valley Hospital
state: Ontario
city: Oshawa
country: Canada
facility: Lakeridge Health Oshawa
state: Ontario
city: Toronto
country: Canada
facility: Odette Cancer Centre- Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network-Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
Study officials:
affiliation: Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
name: Andrew Loblaw
role: STUDY_CHAIR
References: