Clinical Trials /

Nivolumab in Patients With High-Risk Biochemically Recurrent Prostate Cancer

NCT03637543

Description:

This research study is studying an immune-based cancer drug as a possible treatment for prostate cancer. The drug involved in this study is: -Nivolumab

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab in Patients With High-Risk Biochemically Recurrent Prostate Cancer
  • Official Title: A Phase 2 Study of Nivolumab in Patients With High-Risk Biochemically Recurrent Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: 18-249
  • NCT ID: NCT03637543

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
NivolumabOpdivoPD-L1 Positive

Purpose

This research study is studying an immune-based cancer drug as a possible treatment for prostate cancer. The drug involved in this study is: -Nivolumab

Detailed Description

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of an investigational drug to learn whether the drug works in treating a
      specific disease. "Investigational" means that the drug is being studied.

      The FDA (the U.S. Food and Drug Administration) has not approved nivolumab for this specific
      disease but it has been approved for other uses. Nivolumab is an antibody inhibitor of the
      programmed death-1 (PD-1) pathway. By blocking PD-1, this medication may allow the immune
      system to recognize and fight cancer.

      In this research study, the investigators are investigating whether nivolumab has any
      activity in patients who have a rising PSA (prostate specific antigen) after previously
      undergoing surgery or radiation for prostate cancer. Although nivolumab was previously not
      found to have significant effect in advanced prostate cancer after all other therapies had
      failed, based on new research, the investigators are testing whether nivolumab could have a
      greater effect earlier in the disease course and before patients receive hormone therapies.
    

Trial Arms

NameTypeDescriptionInterventions
PD-L1 PositiveExperimental-Nivolumab will be given on day 1 of a 28-day cycle intravenously
  • Nivolumab
PD-L1 NegativeExperimental-Nivolumab will be given on day 1 of a 28-day cycle intravenously
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have signed an informed-consent form indicating that the patient
             understands the purpose of and procedures required for the study and is willing to
             participate in the study.

          -  Patients must have a history of prostate adenocarcinoma (adenocarcinoma must be the
             primary histology; secondary components of variant histologies are acceptable)
             confirmed on biopsy and treated with primary radical prostatectomy (RP) or definitive
             radiation (RT). Prior salvage RT is acceptable.

          -  Patients must have experienced biochemical recurrence (BCR) defined as:

               -  Following primary RP: Any detectable rising PSA after RP (or after salvage RT if
                  performed)

               -  Following primary RT: PSA rise to ≥2 ng/mL above the nadir

               -  No evidence of metastases on conventional imaging (CT or MRI plus bone scan)

          -  PSA doubling time (PSADT) <10 months --PSADT: calculated as per Prostate Cancer
             Working Group 3 (PCWG3) and the Memorial Sloan Kettering Cancer Center calculator:
             (https://www.mskcc.org/nomograms/prostate/psa_doubling_time)

        With linear regression model of normal logarithm of PSA and time, based on:

          -  At least 3 consecutive PSA values with each value ≥0.2 ng/mL

          -  Interval between first and last PSA values is ≥8 weeks but ≤12 months

               -  Most recent PSA ≥2.0 ng/mL

               -  Archival tissue is mandatory, either prostatectomy specimen or (in patients who
                  received primary RT) diagnostic core biopsies. Patients must consent to
                  next-generation sequencing performed on this tissue.

          -  If diagnostic core biopsies are only available tissue, at least 3 cores must be
             involved by tumor

               -  Easteron Cooperative Oncology Group (ECOG) performance status 0-1

               -  Age ≥18 years

               -  Adequate organ and marrow function:

               -  System Laboratory Value

          -  Hematological

          -  White blood cell (WBC) ≥ 2000/µL

          -  Absolute Neutrophil Count (ANC) ≥ 1500/μL

          -  Platelets (Plt) ≥ 100 x103/μL

          -  Hemoglobin (Hgb) > 9.0 g/dL (with or without transfusion)

             -Renal

          -  Serum Creatinine ≤ 2 x ULN

          -  Hepatic

          -  Bilirubin1 ≤ 1.5× upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) ≤ 3 × ULN

          -  Alanine aminotransferase (ALT) ≤ 3 × ULN

               -  Except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL

               -  Baseline testosterone ≥100 ng/dL

               -  Recovery from acute toxicity related to prior therapy, including surgery and
                  radiation, or no treatment-related toxicity ≥ grade 2.

               -  History of prior malignancy or concurrent separate malignancy is not an exclusion
                  criterion so long as the non-prostate malignancy is stable and does not require
                  any treatment.

               -  Able to understand and sign informed consent and adhere to study procedures.

               -  Male patients whose female partners are of reproductive potential must agree to
                  use a contraception during the trial period

        Exclusion Criteria:

          -  Current use of ADT or plan to initiate ADT during trial period

          -  Major surgery or radiation therapy within 14 days of starting study treatment

          -  Subjects with active autoimmune disease. Patients with a history of autoimmune disease
             that has not required systemic immunosuppressive therapy or does not threaten vital
             organ function including central nervous system, heart, lungs, kidneys, skin, and
             gastrointestinal tract will be allowed.

          -  Known history of immune deficiencies or chronic viral infections including HIV,
             hepatitis B (HBV), and hepatitis C (HCV) (patients with prior therapy for HBV or HCV
             is permitted if viral clearance was documented).

          -  Concurrent medical condition requiring use of systemic corticosteroids with prednisone
             >10 mg per day or equivalent. Use of inhaled, nasal, and topical steroids (applied to
             small body areas) is allowed.

          -  Current use (within past 4 weeks) of other prohibited medications including
             anti-cancer therapies, hormonal therapies, 5-alpha reductase inhibitors, and
             alternative medications known to alter PSA (e.g. phytoestrogens and saw palmetto).

          -  Prior treatment with immune checkpoint inhibitors. (Prior cancer vaccines are
             allowed.)

          -  Serious intercurrent medical or psychiatric illness that, in the judgment of the
             investigator, would interfere with patient's ability to carry out the treatment
             program
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease Control
Time Frame:12 weeks
Safety Issue:
Description:Proportion of patients with high-risk biochemically-recurrent (BCR) prostate cancer (PCa) that experiences decline or stabilization in PSA (without symptomatic/radiographic progression) after 12 weeks of nivolumab treatment

Secondary Outcome Measures

Measure:Maximal change in prostate specific antigen (PSA) during nivolumab treatment
Time Frame:2 years
Safety Issue:
Description:
Measure:Best PSA response during nivolumab treatment as an absolute change relative to baseline
Time Frame:2 years
Safety Issue:
Description:
Measure:Change in PSA doubling time (PSADT) at end-of-study relative to baseline
Time Frame:2 years
Safety Issue:
Description:
Measure:Time from enrollment to development of radiographic metastatic disease
Time Frame:2 years
Safety Issue:
Description:
Measure:Time from enrollment to initiation of androgen deprivation therapy (ADT)
Time Frame:2 years
Safety Issue:
Description:
Measure:Treatment-related adverse events as assessed by CTCAE v5.0
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Beth Israel Deaconess Medical Center

Trial Keywords

  • Prostate Cancer

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