DURVALUMAB for Prostate cancer | Oligometastatic hormone-sensitive prostate cancer

Inclusion criteria

• {"criterion_text":"- 1.\tWritten informed consent obtained from the patient prior to performing any protocol-related procedures, including screening evaluations\n- 10.\tBody weight > 30kg\n- 11.\tLife expectancy of > 24 months\n- 12.\tPatient 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\n- 13.\tSocial insurance\n- 2.\tAge > or = 18 years at time of study entry\n- 3.\tHistologically proven diagnosis of prostate cancer (PCa)\n- 4.\tPCa 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.\n- 5.\tAmended 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\t≤ 4 cm for bone metastases o\t≤ 2 cm for lymph node metastases\n- 6.\tWHO performance state 0-1\n- 7.\tControlled 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.\n- 8.\tIf 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.\n- 9.\tAdequate normal organ and marrow function as defined below: o\tHaemoglobin ≥9.0 g/dL o\tAbsolute neutrophil count (ANC) ≥ 1.5 x 103 /L (≥ 1500 per mm3) o\tPlatelet count ≥ 75 x 109/L (≥75,000 per mm3) o\tSerum 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. o\tAST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN o\tMeasured 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)\t=\tWeight (kg) x (140 – Age) 72 x serum creatinine (mg/dL)"}

Exclusion criteria

• {"criterion_text":"- 1.\tSerum testosterone level < 8.5 nmol/l\n- 10.\tRelapsed primary tumor\n- 11.\tPerihilar lymphnode metastases\n- 12.\tPrevious irradiation of the oligometastatic site using a dose > 20 Gy less than 5 years ago\n- 13.\tPrevious treatment with a cytotoxic agent for PCa\n- 14.\tTreatment during the past month with products known to influence PSA levels (e.g. fluconazole, finasteride, corticosteroids...)\n- 14. Participation in another clinical study with an investigational product during the last 4 weeks\n- 16.\tConcurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study\n- 17.\tAny prior immune therapy (CTLA-4, PD1 or PD-L1 inhibitor, including durvalumab)\n- 18.\tCurrent or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab,. The following are exceptions to this criterion: \tIntranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) \tSystemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent \tSteroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)\n- 19.\tRadiotherapy 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\n- 2. Vertebral metastases with a minimum distance inferior to 5 mm between GTV and spinal cord\n- 20.\tMajor surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of Durvalumab.\n- 21.\tHistory of allogenic organ transplantation\n- 22.\tActive 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: \tPatients with vitiligo or alopecia \tPatients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement \tAny chronic skin condition that does not require systemic therapy \tPatients without active disease in the last 5 years may be included but only after consultation with the study physician \tPatients with celiac disease controlled by diet alone\n- 23.\tUncontrolled 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\n- 24.\tHistory of another primary malignancy except for \tMalignancy 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 \tAdequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease \tAdequately treated carcinoma in situ without evidence of disease\n- 25.\tHistory of leptomeningeal carcinomatosis\n- 26.\tHistory of active primary immunodeficiency\n- 27.\tActive 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 surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.\n- 28.\tReceipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.\n- 29.\tKnown allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.\n- 3.\tSuppressed\n- 30.\tPrior randomization or treatment in a previous durvalumab clinical study regardless of treatment arm assignment\n- 31.\tMale patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy, whichever is the longer time period\n- 4. Lymph nodes greater than 20 mm\n- 5.\tModified Patient with PSA doubling time less than 3 months and with two metastases or more\n- 6.\tSpinal cord compression\n- 7.\tAny unresolved toxicity NCI CTCAE (5.0) Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria -\tPatients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. -\tPatients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.\n- 8.\tPSA rise while on active treatment (LHRH-agonist, LHRH-antagonist, anti-androgen, maximal androgen blockade, oestrogen)\n- 9.\tLung, Brain, Liver or other visceral metastases"}

Primary endpoints

• {"endpoint_text":"- 3 types of progression are defined and definitions of progression are used and registered according to the recommendations of the prostate cancer clinical trials working group. If a patient meets any of the progression criteria or death from any causes, the patient will be considered to have progressive disease. Calculation will start from randomization until progression or death. 1.\tPSA or biochemical progression 2. Local progression 3. Distant progression","definition_or_measurement_approach":"Progression is defined according to prostate cancer clinical trials working group recommendations as any of: 1) PSA or biochemical progression, 2) Local progression, or 3) Distant progression. If a patient meets any progression criterion or dies from any cause they are considered to have progressive disease. Calculation starts from randomization until progression or death."}

Secondary endpoints

• {"endpoint_text":"- a) Time from randomization to the date of PSA or biochemical progression as defined above","definition_or_measurement_approach":"Time from randomization to date of PSA or biochemical progression as defined in the primary endpoint."}
• {"endpoint_text":"- b) Time from randomization to the date of any event of PSA progression, local progression, distant progression, or death","definition_or_measurement_approach":"Time from randomization to first occurrence of any of PSA progression, local progression, distant progression, or death."}
• {"endpoint_text":"- c) Time from randomization to the date of any event of local progression, distant progression, or death","definition_or_measurement_approach":"Time from randomization to first occurrence of local progression, distant progression, or death."}
• {"endpoint_text":"- d) Time from randomization to the date of any event of distant progression, or death","definition_or_measurement_approach":"Time from randomization to first occurrence of distant progression or death."}
• {"endpoint_text":"- e)Quality of life scoring using the EORTC QLQ-C30 supplemented with QLQ-PR25 and pain with BPI + EVA","definition_or_measurement_approach":"Quality of life assessed by EORTC QLQ-C30 supplemented with QLQ-PR25; pain assessed with BPI and EVA."}
• {"endpoint_text":"- f) ADT will be started in both arms at time of polymetastatic disease, local progression of metastases (defined above) or symptoms. In case of a metachronous oligometastatic recurrence, a retreatment with radiotherapy or surgery is allowed. Calculation will start from randomization until ADT is started.","definition_or_measurement_approach":"Time from randomization to initiation of androgen deprivation therapy (ADT); ADT start criteria include polymetastatic disease, local progression, or symptoms."}
• {"endpoint_text":"- g)\tProstate cancer specific survival (PCSS) will be calculated from randomization until Prostate cancer death or complications related to the protocol treatment","definition_or_measurement_approach":"Time from randomization until death due to prostate cancer or complications related to protocol treatment."}
• {"endpoint_text":"- h)\tOverall survival (OS) will be calculated from randomization until death from any cause","definition_or_measurement_approach":"Time from randomization until death from any cause."}
• {"endpoint_text":"- Time to first symptomatic event will be calculated from randomization until the event of symptoms due to metastatic disease","definition_or_measurement_approach":"Time from randomization until first symptomatic event attributable to metastatic disease."}
• {"endpoint_text":"- j)\tAcute and late toxicity due to radiotherapy will be scored using the Common toxicity criteria version 5.0","definition_or_measurement_approach":"Radiotherapy-related acute and late toxicity graded using Common Toxicity Criteria (CTCAE) version 5.0."}
• {"endpoint_text":"- k)\tPlasma biomarkers measurements","definition_or_measurement_approach":"Measurement of specified plasma biomarkers (details not specified in the record)."}
• {"endpoint_text":"- l)\tImmune response monitoring","definition_or_measurement_approach":"Monitoring of immune response parameters (details not specified in the record)."}
• {"endpoint_text":"- m)\tPDL1 expression in CTCs","definition_or_measurement_approach":"Assessment of PD-L1 expression in circulating tumor cells (CTCs)."}
• {"endpoint_text":"- n)\tTime to castration resistance","definition_or_measurement_approach":"Time from randomization to development of castration-resistant disease (definition per protocol)."}
• {"endpoint_text":"- o)\tAssociation between the PSA 3, 5, and 7-months after SBRT (in 3 classes : <0.1 ng/mL / 0.1-0.49 / >0.5 ng/mL), and dPFS, PCSS and OS (ref : PMID: 29727915, PMID: 24739897). Exploratory analyses investigating association between other PSA threshold values at different timepoints with survival outcomes will be performed","definition_or_measurement_approach":"Exploratory analyses associating PSA categories at 3, 5, and 7 months post-SBRT with distant PFS, prostate-cancer specific survival, and overall survival."}
• {"endpoint_text":"- NED is defined as patients meeting all of the following: - Alive - No biochemical recurrence (defined as PSA >0.5 ng/ml + nadir and rising) - No distant progression - No local progression - No subsequent therapy for PC","definition_or_measurement_approach":"Binary early endpoint 'No Evidence of Disease (NED)' defined as alive, no biochemical recurrence (PSA >0.5 ng/ml + nadir and rising), no distant progression, no local progression, and no subsequent therapy for prostate cancer."}

France

Earliest CTIS Part Ii Submission Date

12-06-2024

Latest Decision Or Authorization Date

05-07-2024

Processing Time Days

23

Number Of Sites

16

Number Of Participants

96

Primary sponsor

Full Name

Institut De Cancerologie De L Ouest

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France