SRT Versus SRT+ADT in Prostate Cancer (SPA)

Marco Lorenzo Bonu

Status and phase: Enrolling; Phase 3

Conditions: Prostate Cancer

Treatments: Drug: Triptorelin Embonate; Drug: Bicalutamide 50 mg

Study type: Interventional

Funder types: Other

Identifiers

NCT05019846

SPA Trial vers. 1.1

2020-005754-23 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 310 estimated patients

Sex: Male

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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310 participants in 2 patient groups

SRT+ADT

Experimental group

Description:

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

Treatment:

Drug: Bicalutamide 50 mg

Drug: Triptorelin Embonate

SRT alone

No Intervention group

Description:

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).