Trial of Pembrolizumab in Metastatic Castration Resistant Prostate Cancer

NCT03506997 | Unknown Phase 2 DMC

• 2 other identifiers: ICR-CTSU/2016/100602017-000931-15
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

PERSEUS1 is an open-label, single arm, phase II trial evaluating the efficacy of Pembrolizumab in metastatic castration resistant prostate cancer (mCRPC) patients (Part A) with a biomarker enrichment stage (Part B) if efficacy is shown in part A.

Conditions

Castration-resistant Prostate Cancer

Keywords

Immune checkpoint inhibitor; Pembrolizumab

Outcome Measures

Primary Outcomes (1)

• To evaluate tumour response

  Responses will be defined on the basis of the following outcomes; if any of these occur patients will be considered to have responded: * Objective response by iRECIST 1.1;or * CTC count conversion from \>5 to \<5 * PSA decline of ≥50%. Responses will need confirmation by a second consecutive value obtained four or more weeks after the first value indicated a response. Evaluable patients with no confirmed response as defined above will be classified as non-responders. Response will be evaluated 6 months post-trial entry. The last value of PSA, CTC count, CT scan/bone scan/WB-MRI on or up to 28 days before the date of first study treatment will be used as the baseline value for this assessment.

  6 months post trial entry

Secondary Outcomes (7)

• Radiological progression-free survival (rPFS)

  From date of randomisation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Time to radiological progression

  From date of randomisation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Progression free survival

  From date of randomisation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Time to PSA progression

  From date of randomisation until the date of first documented PSA progression or date of death from any cause, whichever came first, assessed up to 100 months

• Duration of PSA response

  From date of first decline by at least 50% until the time time there is an increase of 25% of PSA nadir or date of death from any cause, whichever came first, assessed up to 100 months

Other Outcomes (9)

• Exploratory: • Molecular endpoints from both diagnostic archival FFPE tumour tissue (when available) and fresh mCRPC tumour tissue

  From date of randomisation until the end of trial or date of death from any cause, whichever came first, assessed up to 100 months

• Exploratory: • Molecular endpoints from both diagnostic archival FFPE tumour tissue (when available) and fresh mCRPC tumour tissue

  From date of randomisation until the end of trial or date of death from any cause, whichever came first, assessed up to 100 months

• Exploratory: • Molecular endpoints from both diagnostic archival FFPE tumour tissue (when available) and fresh mCRPC tumour tissue

  From date of randomisation until the end of trial or date of death from any cause, whichever came first, assessed up to 100 months

Study Arms (1)

Pembrolizumab

EXPERIMENTAL

Pembrolizumab will be given at a dose of 200mg IV every 3 weeks for a maximum of two years

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Pembrolizumab 200mg given as a 30 minute intravenous (IV) infusion, on day 1 of each 3 week cycle. Patients may continue with pembrolizumab treatment as long as they remain free from intolerable toxicity for a maximum of two years, if in the Investigator's opinion they are receiving clinical benefit, and/or they do not meet any discontinuation criteria.

Also known as: Keytruda; MK-3475

Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Male, aged 18 years or older.
• Histologically confirmed metastatic castrate resistant adenocarcinoma of the prostate. 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.
• Identified high mutational load (defined as 11 or more mutations per targeted panel - see Section 5.5 below) on next generation sequencing and/or a DNA repair defect that can increase mutation load including MMR deficiency and/or high MSI by next generation sequencing.
• Patients with no measurable disease and only widespread bone disease must have a CTC count \>5.
• Willing and able to comply with the follow-up schedule and the requirements of the biomarker studies including the paired fresh tumour biopsies.
• Written informed consent.
• Prior treatment with at least one of the approved treatments for mCRPC (i.e. Abiraterone, Enzalutamide, Docetaxel, Cabazitaxel, Radium 223).
• 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.
• 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. The PSA value at the Screening visit should be ≥ 2 µg/L (2 ng/ml) if there is no measurable disease; 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.
• Radiographic progression of soft tissue disease by iRECIST criteria or of bone metastases by PCWG3 criteria with two or more confirmed new bone lesions on a bone scan/wb-MRI with or without PSA progression.
• 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 continued throughout the study.

You may not qualify if:

• \. 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.
• \. 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.
• \. 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 the expected start or after any dose of pembrolizumab. Examples include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, seasonal flu, H1N1 flu, rabies, BCG, and typhoid vaccine.
• \. Patients receiving growth factors including, but not limited to, granulocyte colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (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.
• \. Uncontrolled intercurrent cardiovascular disease as symptomatic congestive heart failure (New York Heart Association 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).
• \. Any psychiatric illness/social situations that would limit compliance with study requirements.
• \. Any acute toxicity due to prior chemotherapy and / or radiotherapy that has not resolved to a NCI-CTCAE v4 grade ≤1 with the exception of chemotherapy induced alopecia and grade 2 peripheral neuropathy.
• \. 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.
• \. 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.
• \. Patients with symptomatic or impending cord compression unless appropriately treated beforehand and clinically stable and asymptomatic.
• \. Any chronic respiratory disease. 13. 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);
• Cytotoxic agents (such as alkylating agents or antimetabolites);
• Antibodies (polyclonal antibodies; monoclonal antibodies different from pembrolizumab);
• Drugs acting on immunophilins (cyclosporin, tacrolimus, sirolimus);

Sponsors & Collaborators

• Institute of Cancer Research, United Kingdom: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

The Royal Marsden Hospital

Sutton, Surrey, SM2 5PT, United Kingdom

RECRUITING

MeSH Terms

Interventions

pembrolizumab

Study Officials

• Johann de Bono

  The Institute of Cancer Research/The Royal Marsden NHSFT

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephanie M Burnett, BSc

CONTACT

02087224261; perseus-icrctsu@icr.ac.uk

Ajit Sarvadikar

CONTACT

020 8722 4329; perseus-icrctsu@icr.ac.uk

Study Design

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

Model Details: Two stage Simon Minimax design phase II trial, with 90% power and 5% type I error to discard treatment if \<20% responses are observed and detect activity \>40%

Study Record Dates

• First Submitted: March 12, 2018
• First Posted: April 24, 2018
• Study Start: November 27, 2018
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2025
• Last Updated: July 22, 2020

Record last verified: 2020-07

Locations

GB (1)