Prostate Cancer With OligometaSTatic Relapse: Combining Stereotactic Ablative Radiotherapy and Durvalumab (MEDI4736)

NCT03795207 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: ICO-N-2017-08
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Node; Prostate; Bone Metastases; Prostate Cancer Patients

Keywords

Node; Prostate; Bone Metastases; Prostate cancer patients; SBRT (Stereotactic body radiation therapy); Durvalumab; TEP-FCH; TEP-PSMA

Outcome Measures

Primary Outcomes (1)

• Two-years Progression-free survival

  The primary outcome will be progression-free survival, defined as the time from randomization until a biochemical-clinical failure

  54 months

Secondary Outcomes (8)

• Health-related quality of life

  through study completion, an average of 7.5 year

• Health-related quality of life

  through study completion, an average of 7.5 year

• Androgen deprivation therapy free survival

  through study completion, an average of 7.5 year

• Prostate cancer specific survival

  through study completion, an average of 7.5 year

• Overall survival

  through study completion, an average of 7.5 year

Study Arms (2)

Arm SBRT + DURVALUMAB

EXPERIMENTAL

Radiation (SBRT) + Immunotherapy treatment (Durvalumab) 64 patients will be enrolled in this arm Durvalumab, will be started one month prior to SBRT and then given for a total of 12 months. Patient will receive one injection per months (1500 mg/cycle) SBRT will be started one month after Durvalumab and patients will receive 3 fractions of radiation

Combination Product: SBRT + Durvalumab

Arm SBRT

ACTIVE COMPARATOR

Radiation (SBRT) 32 patients will be enrolled in this arm Patients will receive only 3 fractions of radiation

Radiation: SBRT

Interventions

SBRT + Durvalumab COMBINATION_PRODUCT

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

Arm SBRT + DURVALUMAB

SBRT RADIATION

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

Arm SBRT

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained from the patient prior to performing any protocol-related procedures, including screening evaluations
• Age \> or = 18 years at time of study entry
• Histologically proven diagnosis of prostate cancer (PCa)
• PCa patients with a biochemical recurrence "Rising PSA" following treatment with curative intent (radical prostatectomy, primary radiotherapy or a combination of both) as defined by the EAU guidelines.
• A maximum of 5 bone or lymph node metastases, seen only on FCH-PET CT or Ga-PSMA PET CT, not seen on conventional imaging assessments (bone scan or thorax, abdomen and pelvis CT scan).
• WHO performance state 0-1
• Controlled primary tumor. In case the PSA \> 0,2 ng/ml in the postoperative setting patients are eligible if a multiparametic MRI or PET scan of the prostate bed rules out a local relapse.
• Patients after primary radiotherapy should undergo MRI of the prostate according to the European Society of Urogenital Radiology (ESUR) guidelines to rule out local relapse. In case of a suspicious lesion, a biopsy should confirm local recurrence and patients should be referred for local salvage prostatectomy when distant metastases are ruled out. If MRI rules out local relapse, patients are eligible.
• Adequate normal organ and marrow function as defined below:
• Haemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 x 103 /L (≥ 1500 per mm3)
• Platelet count ≥ 75 x 109/L (≥75,000 per mm3)
• Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysishaemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
• AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN
• Measured creatinine clearance (CL) ≥ 40 ml/min or Calculated creatinine CL ≥ 40 ml/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance: Creatinine CL (ml/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)

You may not qualify if:

• Serum testosterone level \< 8.5 nmol/ml
• Vertebral metastases with a minimum distance inferior to 5 mm between GTV (gross tumor volume) and spinal cord
• Visceral metastases
• Bone metastases seen on bone scan
• Lymph nodes greater than 20 mm
• PSA doubling time less than 6 months
• Spinal cord compression
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
• PSA rise while on active treatment (LHRH-agonist, LHRH-antagonist, anti-androgen, maximal androgen blockade, oestrogen)
• Lung, Brain, Liver or other visceral metastases
• Relapsed primary tumor
• Perihilar lymphnode metastases
• Previous irradiation of the oligometastatic site using a dose \> 20 Gy less than 5 years ago.
• Previous treatment with a cytotoxic agent for PCa

Sponsors & Collaborators

• Institut Cancerologie de l'Ouest: lead
• AstraZeneca: collaborator

Study Sites (9)

Institut Bergonie

Bordeaux, 33076, France

Location

CHRU de Brest

Brest, 29200, France

Location

Centre Georges François Leclerc

Dijon, 21079, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Chbs Lorient

Lorient, 56100, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Institut de Cancérologie de Montpellier

Montpellier, 34298, France

Location

Hospices Civils de Lyon

Pierre-Bénite, 69310, France

Location

ICO

Saint-Herblain, 44805, France

Location

MeSH Terms

Interventions

Radiosurgery; durvalumab

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• STEPHANE SUPIOT

  INSTITUT DE CANCEROLOGIE DE L'OUEST

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2019
• First Posted: January 7, 2019
• Study Start: March 21, 2019
• Primary Completion: December 27, 2023
• Study Completion (Estimated): December 27, 2027
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (9)