SRT Versus SRT+ADT in Prostate Cancer (SPA)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Triptorelin Embonate; Drug: Bicalutamide 50 mg

• Study Type: Interventional
• Enrollment (Anticipated): 310
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • BS
    • Brescia, BS, Italy, 25123
      • Recruiting
      • ASST Spedali Civili of Brescia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SRT+ADT; 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	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
No Intervention: SRT alone; Patients in ARM B will be treated with SRT on prostate alone at a total dose of 36.25 Gy administered daily or on alternate days in 5 fraction (7.25 Gy/fraction).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
biochemical disease free survival	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.	outcome will be evaluated at the completion of 5 years of follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease free survival	from the date of the end of radiotherapy to the date of relapse (any) or last Follow-up visit.Outcome is mesured in months.	outcome will be evaluated at the completion of 5 years of follow-up
freedom from local recurrence	from the date of the end of radiotherapy to the date of local relapse or last Follow-up visit. Outcome is mesured in months.	outcome will be evaluated at the completion of 5 years of follow-up
freedom from regional recurrence	from the date of the end of radiotherapy to the date of regional relapse or last Follow-up visit. Outcome is mesured in months.	outcome will be evaluated at the completion of 5 years of follow-up
freedom from distant metastasis	from the date of the end of radiotherapy to the date of metastatic relapse or last Follow-up visit. Outcome is mesured in months.	outcome will be evaluated at the completion of 5 years of follow-up
Overall survival	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.	outcome will be evaluated at the completion of 5 years of follow-up
quality of life, prostate related quality of life in prostate cancer	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	12 weeks after SRT, 3, 6 and 12 months after SRT
quality of life, prostate related quality of life questionnarire	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.	12 weeks after SRT, 3, 6 and 12 months after SRT
patients reported outcome, erectile function assessment,	scored with questionnaire International Index of Erectile Function 5 (IIEF from 25 (best) to 5 (worse))	12 weeks after SRT, 3, 6 and 12 months after SRT
patients reported outcome, prostate related symptoms assessment	scored with questionnaire Internation Prostate syntoms scale (IPSS, from 0 (best) to 35 (worse))	12 weeks after SRT, 3, 6 and 12 months after SRT
Clinician reported Acute Toxicity, assessed with CTCAE 5.0 scales	Outcome is mesured in 0-5 scale (higher scale worse toxicity)	from the beginning of treatment until 6 months after SRT
Clinician reported Late Toxicity, assessed with CTCAE 5.0 scales	Outcome is mesured in 0-5 scale (higher scale worse toxicity)	from 6 months after SRT 5 years of follow-up

Collaborators and Investigators

• Sponsor: Marco Lorenzo Bonu
• Collaborators: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2021
• Primary Completion (Anticipated): December 1, 2025
• Study Completion (Anticipated): December 1, 2029

Study Registration Dates

• First Submitted: August 2, 2021
• First Submitted That Met QC Criteria: August 18, 2021
• First Posted (Actual): August 25, 2021

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 13, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: randomized trial; SBRT; ADT; SRT; high risk prostate cancer; unfavourable intermediate risk prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Androgen Antagonists; Luteolytic Agents; Bicalutamide; Triptorelin Pamoate
• Other Study ID Numbers: SPA Trial vers. 1.1; 2020-005754-23 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Concurrently with the publication of study results concerning efficacy, we will deliver a completely deidentified data set to an appropriate data archive for sharing purposes.
• IPD Sharing Time Frame: Concurrently with the publication of study results concerning efficacy, we will deliver a completely deidentified data set to an appropriate data archive for sharing purposes.
• IPD Sharing Access Criteria: explicit request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No