SRT Versus SRT+ADT in Prostate Cancer

Official title

Stereotactic Prostate Radiotherapy With or Without Androgen Deprivation Therapy, a Phase III, Multi-institutional Randomized-controlled Trial. The SPA Trial.

Overview

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.

Interventions

• Drug Triptorelin Embonate
  single administration before SRT starting
• Drug Bicalutamide 50 mg
  1 dose each day, 7 days before LHRH until 10 days after LHRH administration

Primary outcome measures

• biochemical disease free survival [Time frame: outcome will be evaluated at the completion of 5 years of follow-up]

Secondary outcome measures (11)

• Disease free survival [Time frame: outcome will be evaluated at the completion of 5 years of follow-up]
• freedom from local recurrence [Time frame: outcome will be evaluated at the completion of 5 years of follow-up]
• freedom from regional recurrence [Time frame: outcome will be evaluated at the completion of 5 years of follow-up]
• freedom from distant metastasis [Time frame: outcome will be evaluated at the completion of 5 years of follow-up]
• Overall survival [Time frame: outcome will be evaluated at the completion of 5 years of follow-up]
• quality of life, prostate related quality of life in prostate cancer [Time frame: 12 weeks after SRT, 3, 6 and 12 months after SRT]
• quality of life, prostate related quality of life questionnarire [Time frame: 12 weeks after SRT, 3, 6 and 12 months after SRT]
• patients reported outcome, erectile function assessment, [Time frame: 12 weeks after SRT, 3, 6 and 12 months after SRT]
• patients reported outcome, prostate related symptoms assessment [Time frame: 12 weeks after SRT, 3, 6 and 12 months after SRT]
• Clinician reported Acute Toxicity, assessed with CTCAE 5.0 scales [Time frame: from the beginning of treatment until 6 months after SRT]
• Clinician reported Late Toxicity, assessed with CTCAE 5.0 scales [Time frame: from 6 months after SRT 5 years of follow-up]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Italy · 1 center

• ASST Spedali Civili of Brescia — Brescia

Identifiers

NCT: NCT05019846 · SPA Trial vers. 1.1 · 2020-005754-23

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗