ivolumab and ipilimumab treatment in prostate cancer with an immunogenic signature

Phase 1

• Conditions: Metastatic castrate resistant prostate cancer (prostate adenocarcinoma); MedDRA version: 21.0 Level: LLT Classification code 10001198 Term: Adenocarcinoma of the prostate metastatic System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-004091-21-GB
• Lead Sponsor: niversity College London

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-07-11
• Last Update Posted: 16 December 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 35

Inclusion Criteria

Inclusion criteria for Pre-Screening (Assessment of ImS):
• Metastatic castrate resistant prostate cancer.
• Histologically confirmed prostate adenocarcinoma.
• Patient has archival prostate cancer tissue available or has disease amenable to biopsy and is willing to undergo a new biopsy for assessment of ImS. Disease amenable to biopsy is:
oSoft tissue lesion meeting RECIST criteria that in the opinion of clinician and interventional radiologist is safe to biopsy, or
oBone lesion that is deemed suitable to biopsy by a suitably trained clinician.
• Men =18 years.
• Adequate venous access for administration of treatment and collection blood samples for exploratory biological samples.
• Life expectancy of >6 months.
• Has had or is having =1 line of systemic treatment for CRPC, or is currently having first line systemic treatment for mCRPC.
• Reasonable expectation that the patient does currently, or will within the next 3 months, have progressive disease and fulfil all eligibility criteria for trial treatment

Inclusion Criteria for Main Study (Treatment):
• Metastatic castrate resistant prostate cancer.
• Histologically confirmed prostate adenocarcinoma.
• Immunogenic signature positive disease
• Patients with disease amenable to biopsy must be willing to have a new biopsy (if new biopsy was not required for assessment of ImS).
• WHO performance status of 0-1.
• Adequate haematological status.
• Adequate liver and renal function.
• Has had 1 line of systemic treatment for CRPC.
• Documented prostate cancer progression within 6 months prior to screening for the Main Study
• Ongoing androgen deprivation with serum testosterone <1.73 nmol/L.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

Exclusion criteria for Assessment of ImS:
• Any history of autoimmune disease, with the exception of patients with a history of autoimmune-related hyperthyroidism or hypothyroidism who are in remission or on a stable dose of thyroid-replacement hormone
• Patients with prior allogeneic stem cell or solid organ transplantation
• Active invasive malignancy in the previous 2 years excluding non-melanoma skin cancer.
• History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organising pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan (History of radiation pneumonitis in the radiation field is permitted).
• Patients with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
• Patients with the following risk factors for bowel perforation:
oHistory of acute diverticulitis or intra-abdominal abcess in the last 3 years
oHistory of GI obstruction or abdominal carcinomatosis
• History of grade =2 peripheral neuropathy.
• Prior treatment with Sipuleucel-T, immune checkpoint targeting agents or other novel immune-oncology agents
• Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to enrolment, unstable arrhythmias, or unstable angina.
• Patients with uncontrolled Type 1 diabetes mellitus. Patients controlled on a stable insulin regimen are eligible.
• Patients with uncontrolled adrenal insufficiency.
• Known active hepatitis B or C infection.
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.

Exclusion criteria for treatment:
All exclusion criteria to exclude patients from Assessment of ImS apply
• Patients with risk factors for bowel perforation.
• Patients must not have had systemic corticosteroid therapy (>10mg daily prednisone equivalent) for 14 days prior to study entry, or concomitant use of other immunosuppressive medications. The use of inhaled corticosteroids, physiologic replacement doses of glucocorticoids (i.e., for adrenal insufficiency), and mineralocorticoids (e.g., fludrocortisone) is allowed.
• Administration of a live, attenuated vaccine within 4 weeks prior to enrolment or anticipation that such a live, attenuated vaccine will be required during the study.

Study & Design

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