Androgen Suppression Combined With Nodal Irradiation and Dose Escalated Prostate Treatment

Prostate Cancer Clinical Trial

— ASCENDE-SBRT  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06235697
• Other study ID #: CCTG-PR24
• Secondary ID: NCI-2023-09091CC
• Status: Recruiting
• Phase: Phase 3
• Start date: April 25, 2024
• Est. completion date: April 30, 2033

Study information

• Verified date: April 2024
• Source: Canadian Cancer Trials Group
• Contact: Wendy Parulekar
• Phone: 613-533-6430
• Email: wparulekar[@]ctg.queensu.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)?

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 710
• Est. completion date: April 30, 2033
• Est. primary completion date: October 31, 2032
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Radiation:
• Radiation
46Gy / 23 fractions of EBRT to pelvis and prostate + LDR or HDR boost to prostate + Adjuvant ADT: Unfavourable Intermediate Risk: 6 months or High / Very High Risk: 24 months
• Radiation SBRT only
25Gy / 5 fractions to pelvis + 40 Gy / 5 fractions to prostate (SBRT)

Locations

Country	Name	City	State
Canada	Odette Cancer Centre, Sunnybrook Health Sciences Centre	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Canadian Cancer Trials Group	NRG Oncology

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		8.6 years
Secondary	Safety and tolerability assessed by CTCAE v5.0		8.6 years
Secondary	PSA response at 4 years compared using a Cochran-Mantel-Haenszel (CMH) test		8.6 years
Secondary	Metastasis-free Survival compared using the Gray's test		8.6 years
Secondary	Cause-specific Survival compared using the Gray's test		8.6 years
Secondary	Overall Survival analysed using a Cox proportional hazards model and graphically described using the Kaplan-Meier method		8.6 years
Secondary	Participant-reported outcomes using EPIC-26 questionnaire		8.6 years
Secondary	Participant-reported tolerability using PRO-CTCAE questionnaire		8.6 years
Secondary	Economic Outcomes using EQ-5D-5L	Canadian sites only	8.6 years
Secondary	Economic Outcomes using FACIT-COST	Canadian sites only	8.6 years