| Eligibility |
Inclusion Criteria:
1. Written informed consent obtained from the patient prior to performing any
protocol-related procedures, including screening evaluations
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. 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).
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 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.
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:
- 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)
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
Exclusion Criteria:
1. Serum testosterone level < 8.5 nmol/ml
2. Vertebral metastases with a minimum distance inferior to 5 mm between GTV (gross tumor
volume) and spinal cord
3. Visceral metastases
4. Bone metastases seen on bone scan
5. Lymph nodes greater than 20 mm
6. PSA doubling time less than 6 months
7. Spinal cord compression
8. Any unresolved toxicity NCI CTCAE (v4.03) Grade =2 from previous anticancer therapy
with the exception of alopecia, vitiligo, and the laboratory values defined in the
inclusion criteria
- 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.
9. PSA rise while on active treatment (LHRH-agonist, LHRH-antagonist, anti-androgen,
maximal androgen blockade, oestrogen)
10. Lung, Brain, Liver or other visceral metastases
11. Relapsed primary tumor
12. Perihilar lymphnode metastases
13. Previous irradiation of the oligometastatic site using a dose > 20 Gy less than 5
years ago.
14. Previous treatment with a cytotoxic agent for PCa
15. Treatment during the past month with products known to influence PSA levels (e.g.
fluconazole, finasteride, corticosteroids...)
16. Particimmunotherapyation in another clinical study with an investigational product
during the last 4 weeks
17. 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
18. Any prior immune therapy (CTLA-4, PD1 (Programmed cell death )1 or PD-L1 inhibitor,
including durvalumab)
19. Current or prior use of immunosuppressive medication within 14 days before the first
dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or
systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of
prednisone, or an equivalent corticosteroid. 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)
20. 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
21. Major surgical procedure (as defined by the Investigator) within 28 days prior to the
first dose of Durvalumab.
22. History of allogenic organ transplantation.
23. 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
24. 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
25. 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 immunotherapy 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
26. History of leptomeningeal carcinomatosis
27. History of active primary immunodeficiency
28. Active infection including tuberculosis, hepatitis B (known positive HBV (hepatitis B
virus) surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus
(positive HIV 1/2 antibodies). Patients with a past or resolved HBV (hepatitis B
virus) infection (defined as the presence of hepatitis B core antibody [anti-HBc
(hepatitis B core antigen)] 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.
29. Receipt of live attenuated vaccine within 30 days prior to the first dose of
immunotherapy. Note: Patients, if enrolled, should not receive live vaccine whilst
receiving immunotherapy and up to 30 days after the last dose of immunotherapy.
30. Known allergy or hypersensitivity to any of the study drugs or any of the study drug
excipients.
31. Prior randomization or treatment in a previous durvalumab clinical study regardless of
treatment arm assignment.
32. Male 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.
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