As in other solid tumours, increasing evidence indicates that patients diagnosed with a limited number of prostate cancer metastases, so-called oligometastases, have a better prognosis compared with patients with extensive metastatic disease. Survival of patients with three or fewer metastases was superior compared with patients with more than three lesions. The introduction of novel imaging modalities such as Fluorocholine (FCH), Fuciclovine or Ga-PSMA PET CT has increased the detection of oligometastatic prostate cancer (PCa) recurrence, potentially justifying the use of a metastasis-directed therapy with radiotherapy (RT). Based on several studies, SBRT is now considered as a strongly validated option in oligometastatic prostate cancer. It is increasingly understood that cancers are recognized by the immune system, and, under some circumstances, the immune system may control or even eliminate tumors. Programmed death-ligand 1 (PD-L1) is transmembrane protein that has been speculated to play a major role in suppressing the immune system during particular events. PD-L1 is expressed in a broad range of cancers. Based on these findings, an anti-PD-L1 antibody could be used therapeutically to enhance antitumor immune responses in patients with cancer. Experimental data from multiple cancer models have provided cumulative evidence of an interaction of ionizing radiation with the systemic antitumor immunity and this has created several opportunities in the field. The oligometastatic setting appears to be the most relevant clinical situation to evaluate the immune response generated by radiotherapy and immune modifiers in patients with an intact immune system. The hypothesize is that Durvalumab will enhance immune response following SBRT targeting oligometastatic lesions. In this randomized 2:1 phase II trial of Stereotactic Body Radiation Therapy with or without durvalumab in oligometastatic hormone sensitive prostate cancer patients, Durvalumab will be started one month prior to SBRT to be able to evaluate PSA and immune response to the drug. It will be combined with SBRT and then given adjuvantly for a total of 12 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
96
Durvalumab, MEDI4736, is a immunotherapy, SBRT (stereotactic body radiotherapy) is a procedure that uses high doses of radiation delivered to a precise target. By using special positioning and implanted markers in the body, radiologists are able to deliver a much higher dose of radiation to a cancer than traditional radiation therapy
SBRT (stereotactic body radiotherapy) is a procedure that uses high doses of radiation delivered to a precise target. By using special positioning and implanted markers in the body, radiologists are able to deliver a much higher dose of radiation to a cancer than traditional radiation therapy
Institut Bergonie
Bordeaux, France
CHRU de Brest
Brest, France
Centre Georges François Leclerc
Dijon, France
Centre Oscar Lambret
Lille, France
Chbs Lorient
Lorient, France
Centre Léon Bérard
Lyon, France
Institut de Cancérologie de Montpellier
Montpellier, France
Hospices Civils de Lyon
Pierre-Bénite, France
ICO
Saint-Herblain, France
Two-years Progression-free survival
The primary outcome will be progression-free survival, defined as the time from randomization until a biochemical-clinical failure
Time frame: 54 months
Health-related quality of life
Health-related quality of life will be evaluated using EORTC QLQ-PR25 instruments.Total score is reported
Time frame: through study completion, an average of 7.5 year
Health-related quality of life
Health-related quality of life will be evaluated using self-administered EORTC QLQ-C30 questionnaire. Total score is reported
Time frame: through study completion, an average of 7.5 year
Androgen deprivation therapy free survival
ADT will be started in both arms at time of polymetastatic disease, local progression of metastases or symptoms.
Time frame: through study completion, an average of 7.5 year
Prostate cancer specific survival
Delay from randomization to death
Time frame: through study completion, an average of 7.5 year
Overall survival
Delay from randomization to death
Time frame: through study completion, an average of 7.5 year
Acute toxicity: Common toxicity criteria version 4.03
Common toxicity criteria version 4.03
Time frame: through study completion, an average of 7.5 year
Late toxicity: Common toxicity criteria version 4.03
Common toxicity criteria version 4.03
Time frame: through study completion, an average of 7.5 year
Time to resistance castration
serum testosterone measure
Time frame: through study completion, an average of 7.5 year
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