SRT Versus SRT+ADT in Prostate Cancer

Phase 3

Recruiting

• Conditions: Prostate Cancer
• Interventions: Drug: Triptorelin Embonate; Drug: Bicalutamide 50 mg

• Registration Number: NCT05019846
• Lead Sponsor: Marco Lorenzo Bonu

Brief Summary

To clarify the role of short-term Androgen deprivation therapy (ADT) in the context of intermediate unfavorable and a subclass of high-risk patients treated with prostate Stereotactic radiotherapy (SRT).

In intermediate unfavorable risk group, when choosing standard external beam radiotherapy, short term ADT is superior in terms of biochemical disease free survival (bDFS) to EBRT alone. In high risk disease, results of the combination therapy are even more clear. Prostate SRT has been endorsed as option for primary radical treatment for prostate cancer. In such patients, the benefit of ADT is still unknown and the decision is left to clinical judgement.

For these reasons, it seems to be relevant to propose a randomized, open label, phase III clinical trial of prostate SBRT + 6 months ADT versus prostate SBRT alone in intermediate unfavorable and a subgroup of high risk prostate cancer patients.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-08-02
• Study First Submitted QC: 2021-08-18
• Study First Posted: 2021-08-25
• Study Start: 2021-09-30
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-13
• Last Update Posted: 2023-04-18
• Primary Completion: 2025-12-01
• Study Completion: 2029-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 310

Inclusion Criteria

• Histological confirmation of prostate acinar adenocarcinoma with a minimum of 10 biopsy cores taken

• Prostate protocol MRI for local staging

• Patients belonging to intermediate unfavorable group according to the D'Amico/NCCN risk group classification:

  • -Grade group 3 or/and
  • -2-3 risk factors for intermediate category (PSA 10-20 ng/ml/ Grade group 2-3/ cT2b cT2c) or/and
  • -biopsy cores positive ≥50%

• Patients belonging to a subclass of high risk group according to the D'Amico/NCCN risk group classification:

  • -ISUP group 4 (GS 4+4, 3+5, 5+3) or
  • -cT3a stage or
  • PSA>20

• Eastern Coooperative Oncology Group (ECOG) PS 0-2

• Ability of the patient to understand and sign a written informed consent document

• Ability and willingness to comply with patients reported outcome questionnaires schedule during the study time

• IPSS 0-15

• Prostate Volume less than 100cc

• PSA must be dosed maximum 60 days before randomization

• No pathologic lymph nodes and distant metastasis on PET (fluorocholine) scan or CT scan+bone scan.

• Contraceptive measures for patients with partners with reproductive potential must be explained

Exclusion Criteria

• History of Malignant tumors in the previous 2 years excluding non melanoma cancers of the skin. If a patient presents an anamnesis of malignancy (excluding non melanoma skin cancers) it must be free from disease since 24 months at the time of enrollement.
• Previous prostate surgery other than TURP (at least 6 weeks prior to start of SBRT).
• Previous pelvic RT
• Prior androgen deprivation therapy (excluding 5alpha reductase inhibitors)
• Any prior active treatment for prostate cancer; patients on previous active surveillance are eligible if inclusion criteria are met
• Active severe inflammatory bowel disease
• Bilateral hip prothesis or any implant that could seriously interfere with dosimetric calculations
• Age >80 years.
• cT4a, cT3b or pelvic lymph node involvement
• Controindication or hypersensitivity to the use of Triptoreline
• 5alpha reductase inhibitors not discontinued 4 weeks prior to randomization
• History of bone fractures and fall
• Risk factors for abnormal heart rhythms or QT prolongation.
• Use of concomitant medications that prolong the QT/QTc interval

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SRT+ADT	Triptorelin Embonate	Patients in ARM A will be treated with SRT on the prostate (consecutive days or at alternate days to a total dose of 36.25 Gy administered in 5 fraction (7.25 Gy/fraction) + LHRH analogue (Triptoreline 22.5 mg). An anti-androgen drug (es. Bicalutamide 50 mg) must be administered daily starting from 7 days before LHRH analogue administration to 10 days after to prevent the flare effect
SRT+ADT	Bicalutamide 50 mg	Patients in ARM A will be treated with SRT on the prostate (consecutive days or at alternate days to a total dose of 36.25 Gy administered in 5 fraction (7.25 Gy/fraction) + LHRH analogue (Triptoreline 22.5 mg). An anti-androgen drug (es. Bicalutamide 50 mg) must be administered daily starting from 7 days before LHRH analogue administration to 10 days after to prevent the flare effect

Primary Outcome Measures

Name	Time	Method
biochemical disease free survival	outcome will be evaluated at the completion of 5 years of follow-up	form the date of the end of radiotherapy to the date of PSA meeting protocol criteria for biochemical relapse or last Follow-up visit. Outcome is mesured in months.

Secondary Outcome Measures

Name	Time	Method
freedom from local recurrence	outcome will be evaluated at the completion of 5 years of follow-up	from the date of the end of radiotherapy to the date of local relapse or last Follow-up visit. Outcome is mesured in months.
freedom from regional recurrence	outcome will be evaluated at the completion of 5 years of follow-up	from the date of the end of radiotherapy to the date of regional relapse or last Follow-up visit. Outcome is mesured in months.
Overall survival	outcome will be evaluated at the completion of 5 years of follow-up	from the date of the end of radiotherapy to the date of death 8any cause) or last Follow-up visit. Outcome is mesured in months.
quality of life, prostate related quality of life in prostate cancer	12 weeks after SRT, 3, 6 and 12 months after SRT	scored with questionnaire Expandend Prostate cancer Index Composite-26 (EPIC-26), score scale is 0-100 with higher scores representing better health related quality of life
Disease free survival	outcome will be evaluated at the completion of 5 years of follow-up	from the date of the end of radiotherapy to the date of relapse (any) or last Follow-up visit.Outcome is mesured in months.
quality of life, prostate related quality of life questionnarire	12 weeks after SRT, 3, 6 and 12 months after SRT	scored with questionnaire European organization for research and treatment of cancer PR 25, (EORTC PR 25), All of the scales and single-item measures range in score from 0 to 100. A high score for the Sexual Activity and Sexual Functioning scales represents a high level of functioning, whereas a high score for the Urinary, Bowel, and Hormonal Treatment Related symptoms scales and Incontinence Aid item represents a high level of symptomatology or problems.
patients reported outcome, prostate related symptoms assessment	12 weeks after SRT, 3, 6 and 12 months after SRT	scored with questionnaire Internation Prostate syntoms scale (IPSS, from 0 (best) to 35 (worse))
freedom from distant metastasis	outcome will be evaluated at the completion of 5 years of follow-up	from the date of the end of radiotherapy to the date of metastatic relapse or last Follow-up visit. Outcome is mesured in months.
patients reported outcome, erectile function assessment,	12 weeks after SRT, 3, 6 and 12 months after SRT	scored with questionnaire International Index of Erectile Function 5 (IIEF from 25 (best) to 5 (worse))
Clinician reported Acute Toxicity, assessed with CTCAE 5.0 scales	from the beginning of treatment until 6 months after SRT	Outcome is mesured in 0-5 scale (higher scale worse toxicity)
Clinician reported Late Toxicity, assessed with CTCAE 5.0 scales	from 6 months after SRT 5 years of follow-up	Outcome is mesured in 0-5 scale (higher scale worse toxicity)

Trial Locations

Locations (1)

ASST Spedali Civili of Brescia; 🇮🇹 Brescia, BS, Italy