A Phase II trial of Pembrolizumab in patients with mCRPC
- Conditions
- Metastatic Castration Resistant Prostate CancerTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-000931-15-GB
- Lead Sponsor
- Institute of Cancer Research
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Male
- Target Recruitment
- 100
1.Individual, aged 18 years or older.
2.Histologically confirmed adenocarcinoma of the prostate (tumours with neuroendocrine features are eligible). If the patient does not have a prior histological diagnosis then the planned baseline fresh biopsy may be used for both the purpose of confirming the histological diagnosis prior to trial entry and for subsequent biomarker analysis. All patients must be willing to have fresh biopsies to obtain tumour tissue for biomarker analysis.
3.mCRPC with one of the following:
• MMR defective disease by immunohistochemistry;
• Tumours with evidence of bi-allelic CDK12 loss;
• Tumours with high MSI-NGS with either:
o deleterious MMR gene mutation OR;
o high CD3 (=70th centile) OR;
o HIMUT (=11);
• Tumours with HIMUT with either high CD3 or a deleterious mutation in a DNA
repair gene;
• The presence of DNA repair defects (HR, NHEJ, NER) with high CD3 count;
4.Patients with:
• Measurable soft tissue disease as per iRECIST criteria (with or without bone disease), OR
• Non measurable soft tissue disease as per iIRECIST criteria (with or without bone disease), and a CTC count =>5 cells/7.5 ml and PSA value = 2 µg/L (2 ng/ml)
5.Documented prostate cancer progression as assessed by the investigator with one of the following:
• PSA progression defined by a minimum of three rising PSA levels with an interval of = 1-week between each determination. Patients on systemic glucocorticoids for control of symptoms must have documented PSA progression by PCWG3 while on the same dose of systemic glucocorticoids prior to commencing Cycle1 Day1 of treatment.
• Radiological progression of soft tissue disease by RECIST criteria or of bone metastases by PCWG3 criteria with two or more confirmed new bone lesions on a bone scan/WBMRI with or without PSA progression.
6.Willing and able to comply with the follow-up schedule and the requirements of the biomarker studies including the paired fresh tumour biopsies.
7. Written informed consent.
8.Prior treatment with at least one of the approved treatments for mCRPC (i.e. Abiraterone, Enzalutamide, Docetaxel, Cabazitaxel, Radium 223).
9. At least 28-days washout at trial entry since the completion of prior therapy, including major surgery, chemotherapy and other investigational agents. For hormonal treatment and radiotherapy refer to the guidelines below:
• At least 28-days since the completion of prior flutamide treatment. Patients whose PSA did not decline in response to antiandrogens given as a second line or later intervention will only require a 14-day washout prior to Cycle 1, Day 1.
• At least 42-days since the completion of prior bicalutamide (Casodex) and nilutamide (Nilandron) treatment. Patients whose PSA did not decline for at least 3-months in response to antiandrogens given as second line or later intervention will require only a 14-day washout period prior to Cycle 1 Day 1.
• At least 14-days from any radiotherapy with the exception of a single fraction of radiotherapy for the purposes of palliation (confined to one field) is permitted.
10.Surgically or medically castrated, with testosterone levels of <50 ng/dL (<2.0 nM). If the patient is being treated with LHRH agonists (patient who have not undergone orchiectomy), this therapy must have been initiated at least 4 weeks prior to Cycle 1 Day 1 and must be contin
1.Patients with a history of prior treatment with anti-PD-1, anti-PD-L1,
anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, or anti-CTLA-4 antibodies.
2.Patients who have received any of the following concomitant therapies:
IL-2, interferon or other non-study immunotherapy regimens;
immunosuppressive agents; other investigational therapies; or chronic use
of systemic corticosteroids (used in the management of cancer or non-
cancer-related illnesses) within 1 week prior to first dose. A dose of
10mg of prednisolone or equivalent will be allowed if clinically
indicated.
3.Patients who have received any non-oncology vaccine therapy used for
prevention of infectious diseases including seasonal vaccinations for up
to 28-days prior to or after any dose of pembrolizumab.
4.Patients receiving growth factors including, but not limited to,
G-CSF, GM-CSF, erythropoietin, within 14-days of study drug administration.
Use of such agents while on study is also prohibited. Prior use of growth
factors should be documented in the patient’s medical history.
5.Uncontrolled intercurrent cardiovascular disease as symptomatic
congestive heart failure (NYHA Class III or IV heart disease), unstable
angina pectoris, cardiac arrhythmia, poorly controlled hypertension (defined
as systolic blood pressure of =150mmHg or diastolic blood pressure of >100
mmHg based on a mean of three measurements at approximately 2-minute
intervals).
6.Any psychiatric illness/social situations that would limit compliance
with study requirements.
7.Any acute toxicity due to prior chemotherapy and / or radiotherapy that
has not resolved to a NCI-CTCAE v4.0 grade =1 with the exception of
chemotherapy induced alopecia and grade 2 peripheral neuropathy.
8.Prior malignancy diagnosed within the previous 2-years with a >30%
probability of recurrence within 12-months, with the exception of non-
melanoma skin cancer, and in-situ or non-muscle invasive bladder cancer and
germline MMR defect associated cancers that have been completely resected.
9.Patients with myelodysplastic syndrome or acute myeloid leukaemia.
10.Patients with known active central nervous system (CNS) metastases and/or
carcinomatous meningitis. Subjects with previously treated brain
metastases may participate provided they are stable (without evidence of
progression by imaging for at least four weeks prior to the first dose of
trial treatment and any neurologic symptoms have returned to baseline),
have no evidence of new or enlarging brain metastases, and are not using
steroids for at least 7 days prior to trial treatment. This exception
does not include carcinomatous meningitis which is excluded regardless of
clinical stability.
11.Patients with symptomatic or impending cord compression unless
appropriately treated beforehand and clinically stable and asymptomatic.
12.Any immunological disorder requiring treatment with immunosuppressive
treatments:
•High dose of steroids (low dose of steroids as 10mg of prednisolone or
equivalent are allowed if the patient is not able to discontinue this
treatment; patient needs to be on a stable dose for at least 4-weeks
before the enrolment);
•Cytotoxi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method