Clinical Trials /

Nivolumab and Ipilimumab Treatment in Prostate Cancer With an Immunogenic Signature

NCT03061539

Description:

The primary objective is to test the following hypothesis: Patients with metastatic castrate resistant prostate cancer that have progressed following at least one line of therapy and have an immunogenic signature will respond to combined PD-1 and CTLA4 inhibition.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab and Ipilimumab Treatment in Prostate Cancer With an Immunogenic Signature
  • Official Title: Nivolumab and Ipilimumab Treatment in Prostate Cancer With an Immunogenic Signature

Clinical Trial IDs

  • ORG STUDY ID: CA209-935
  • NCT ID: NCT03061539

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
Nivolumab & IpilimumabNivolumab & Ipilimumab

Purpose

The primary objective is to test the following hypothesis: Patients with metastatic castrate resistant prostate cancer that have progressed following at least one line of therapy and have an immunogenic signature will respond to combined PD-1 and CTLA4 inhibition.

Detailed Description

      This is a single arm phase II trial designed to assess the efficacy of nivolumab + ipilimumab
      in patients with metastatic castrate resistant prostate cancer that have progressed following
      at least 1 line of therapy and have an specified immunogenic signature. The immunogenic
      signature is defined by the presence of at least one of the following:

        -  Mismatch repair deficiency by IHC

        -  Defective DNA repair detected by a targeted sequencing panel

        -  High inflammatory infiltrate defined on multiplexed IHC criteria.

      Treatment consists of :

        -  Nivolumab 1 mg/kg + ipilimumab 3 mg/kg every three weeks for a maximum of 4 doses

        -  6 week gap after last combination dose

        -  480 mg flat dose of nivolumab every 4 weeks for up to one year, or until progression,
           unacceptable toxicity or withdrawal of consent.

      Patients must have ongoing androgen deprivation to maintain serum testosterone < 1.73 nmol/L.
    

Trial Arms

NameTypeDescriptionInterventions
Nivolumab & IpilimumabExperimentalPatients will receive Nivolumab 1 mg/kg + ipilimumab 3 mg/kg every three weeks for a maximum of 4 doses followed by a 6 week gap after last combination dose. The patients will then receive 480 mg flat dose of nivolumab every 4 weeks for up to one year, or until progression, unacceptable toxicity or withdrawal of consent.
  • Nivolumab & Ipilimumab

Eligibility Criteria

        Inclusion Criteria:

          -  Metastatic castrate resistant prostate cancer.

          -  Histologically confirmed prostate adenocarcinoma.

          -  Patient has archival prostate cancer tissue available or is willing to undergo a new
             biopsy.

          -  Immunogenic biomarker positive disease - see Appendix 1 NB patients will be included
             in the trial if they meet all other eligibility criteria. Analysis of the ImS will
             take place after registration. Patients who do not have ImS positive disease will be
             withdrawn from the trial.

          -  WHO performance status of 0-1.

          -  Adequate haematological status.

          -  Adequate liver and renal function.

          -  Has had 1 or more lines of systemic treatment for mCRPC.

          -  Documented prostate cancer progression within 6 months prior to screening

          -  Ongoing androgen deprivation with serum testosterone <1.73 nmol/L.

        Exclusion Criteria:

          -  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, organizing 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 risk factors for bowel perforation.

          -  History of grade ≥2 peripheral neuropathy.

          -  Received therapeutic oral or intravenous (IV) antibiotics within 14 days prior to
             enrolment (Patients receiving prophylactic antibiotics (e.g., for prevention of a
             urinary tract infection or COPD) are eligible).

          -  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.

          -  Prior treatment with Sipuleucel-T, immune checkpoint targeting agents or other novel
             immune-oncology agents.

          -  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.

          -  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.

          -  Patients with active hepatitis infection (defined as having a positive hepatitis B
             surface antigen [HBsAg] test at screening) or hepatitis C.

          -  Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
             (AIDS)-related illness.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Composite response rate
Time Frame:Up to 5 years following the start of treatment
Safety Issue:
Description:Patients will be considered as having had a treatment response if any one of the following criteria are satisfied: Radiological response (RECIST 1.1) PSA response ≥50% confirmed by a second PSA test at least 4 weeks later (PCWG3 2016) Conversion of CTC count from ≥5 cells/7.5ml at baseline to <5 cells/7.5ml confirmed by a second CTC test at least 4 weeks later (PCWG3 2016)

Secondary Outcome Measures

Measure:Overall survival
Time Frame:From date of registration until the date of first documented date of death from any cause, assessed up to 5 years.
Safety Issue:
Description:
Measure:Radiological progression free survival
Time Frame:From registration to objective disease progression or death from any cause, whichever comes first, assessed up to 5 years
Safety Issue:
Description:
Measure:PSA progression free survival
Time Frame:From registration to PSA progression free survival assessed up to 5 years
Safety Issue:
Description:
Measure:Change in patient reported outcome measures (NCI's PRO-CTCAE)
Time Frame:From registration until 5 years post treatment
Safety Issue:
Description:
Measure:Frequency and severity of adverse events
Time Frame:For 24 months post the start of trial treatment
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University College, London

Trial Keywords

  • Immunogenic signature

Last Updated

March 10, 2020