Prostate cancer with OligometaSTatic relapse: Combining stereotactic Ablative Radiotherapy and Durvalumab (MEDI4736), a randomized phase II trial

Phase 1

• Conditions: oligometastatic hormone sensitive prostate cancer; MedDRA version: 21.0Level: LLTClassification code: 10007463Term: Carcinoma prostatic Class: 10029104; Therapeutic area: Diseases [C] - Male Urogenital Diseases [C12]; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2024-513207-13-00
• Lead Sponsor: Institut De Cancerologie De L Ouest

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-06-03
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 96

Inclusion Criteria

1.Written informed consent obtained from the patient prior to performing any protocol-related procedures, including screening evaluations, 10.Body weight > 30kg, 11.Life expectancy of > 24 months, 12.Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up, 13.Social insurance, 2.Age > or = 18 years at time of study entry, 3.Histologically proven diagnosis of prostate cancer (PCa), 4.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., 5.Amended A maximum of 5 bone or lymph node metastases diagnosed on Ga-PSMA PET CT, OR a maximum of 3 bone or lymph node metastases diagnosed on FCH-PET CT o= 4 cm for bone metastases o= 2 cm for lymph node metastases, 6.WHO performance state 0-1, 7.Controlled primary tumor. In case the PSA > 0,2 ng/ml in the postoperative setting patients are eligible if a multiparametric 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., 8.If ADT has been previously administered to the patient, a minimum of 12 months must have elapsed between the predicted duration of the last injection and inclusion of the patient in the study. For this category of patients, serum testosterone has to be higher than 8.5 nmol/l prior to inclusion., 9.Adequate normal organ and marrow function as defined below: oHaemoglobin =9.0 g/dL oAbsolute neutrophil count (ANC) = 1.5 x 103 /L (= 1500 per mm3) oPlatelet count = 75 x 109/L (=75,000 per mm3) oSerum 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 haemolysis or hepatic pathology), who will be allowed only in consultation with their physician. oAST (SGOT)/ALT (SGPT) =2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =5x ULN oMeasured 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)

Exclusion Criteria

1.Serum testosterone level < 8.5 nmol/l, 10.Relapsed primary tumor, 11.Perihilar lymphnode metastases, 12.Previous irradiation of the oligometastatic site using a dose > 20 Gy less than 5 years ago, 13.Previous treatment with a cytotoxic agent for PCa, 14.Treatment during the past month with products known to influence PSA levels (e.g. fluconazole, finasteride, corticosteroids...), 14. Participation in another clinical study with an investigational product during the last 4 weeks, 16.Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study, 17.Any prior immune therapy (CTLA-4, PD1 or PD-L1 inhibitor, including durvalumab), 18.Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab,. The following are exceptions to this criterion: ?Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) ?Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent ?Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication), 19.Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug, 2. Vertebral metastases with a minimum distance inferior to 5 mm between GTV and spinal cord, 20.Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of Durvalumab., 21.History of allogenic organ transplantation, 22.Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion: ?Patients with vitiligo or alopecia ?Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement ?Any chronic skin condition that does not require systemic therapy ?Patients without active disease in the last 5 years may be included but only after consultation with the study physician ?Patients with celiac disease controlled by diet alone, 23.Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, 24.History of another primary malignancy except for ?Malignancy treated with curative intent and with no known active disease =5 years before the first dose of IP and of low potential risk for recurrence ?Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease ?Adequately treated carcinoma in situ without evidence of disease, 25.History of leptomeningeal carcinomatosis, 26.History of active primary immunodeficiency, 27.Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified