Single Agent Pembrolizumab in Subjects With Advanced Adrenocortical Carcinoma
Condition: Adrenocortical Carcinoma
MeSH terms: Carcinoma; Adrenocortical Carcinoma
Intervention: Pembrolizumab
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pembrolizumab; 15-286

Summary:

      Pembrolizumab is a type of immunotherapy, and the purpose of this study is to find out what
      effects, good and/or bad, pembrolizumab has on you, and your cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Be willing and able to provide written informed consent for the trial.

          -  Be ≥ 18 years of age on day of signing informed consent.

          -  Have histologically- or cytologically- confirmed unresectable or metastatic ACC that
             is considered incurable by local therapies.

          -  Have an ECOG performance status of 0 or 1.

          -  Have measurable disease based on RECIST v1.1

          -  Have provided tissue for PD-L1 biomarker analysis from either archived tissue or a
             newly obtained core or excisional biopsy.

          -  Consent for use of archived tissue for research purposes.

          -  Demonstrate adequate organ function, all screening labs should be performed within 28
             days of treatment initiation.

        Hematological

          -  Absolute neutrophil count (ANC) ≥1,500 /mcL

          -  Platelets ≥100,000 / mcL Renal

          -  Serum creatinine ≤1.5 X upper limit of normal (ULN) OR Measured or calculateda
             creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥60 mL/min
             for subject with creatinine levels > 1.5 X institutional ULN Hepatic

          -  Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total
             bilirubin levels > 1.5 ULN

          -  AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
             Coagulation

          -  International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless
             subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic
             range of intended use of anticoagulants

          -  Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving
             anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use
             of anticoagulants aCreatinine clearance should be calculated per institutional
             standard.

               -  Female subjects of childbearing potential should have a negative urine or serum
                  pregnancy test within 72 hours prior to receiving first dose of study medication.
                  If the urine test is positive or cannot be confirmed as negative, a serum
                  pregnancy test will be required.

               -  Female subjects of childbearing potential should be willing to use 2 methods of
                  birth control or be surgically sterile, or abstain from heterosexual activity for
                  the course of the study through 120 days after the last dose of study medication.
                  Subjects of childbearing potential are those who have not been surgically
                  sterilized or have not been free of menses for >1 year.

               -  Male subjects should agree to use an adequate method of contraception starting
                  with the first dose of study therapy through 120 days after the last dose of
                  study therapy.

        Exclusion Criteria:

          -  Is currently participating in or has participated in a study of an investigational
             agent or using an investigational device within 4 weeks prior to the first dose of
             trial treatment.

          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of trial
             treatment. The use of physiologic doses of corticosteroids for adrenal and pituitary
             insufficiency is not considered a form of systemic steroid therapy and would not
             exclude a subject from the study.

          -  Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not
             recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents
             administered more than 4 weeks earlier.

          -  Has had prior chemotherapy, targeted small molecule therapy within 2 weeks prior to
             study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse
             events due to a previously administered agent.

             °Note: Subjects with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia are an exception to
             this criterion and may qualify for the study.

          -  If subject underwent major surgery, they must have recovered adequately from the
             toxicity and/or complications from the intervention prior to starting therapy.

          -  Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
             skin, or in situ cervical cancer that has undergone potentially curative therapy.

          -  Has known active central nervous system 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 brain metastases for at least 7 days prior to trial treatment. This
             exception does not include carcinomatous meningitis which is excluded regardless of
             clinical stability.

          -  Has an active autoimmune disease requiring systemic treatment within the past 3 months
             or a documented history of clinically severe autoimmune disease, or a syndrome that
             requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or
             resolved childhood asthma/atopy would be an exception to this rule. Subjects that
             require intermittent use of bronchodilators or local steroid injections would not be
             excluded from the study. Subjects with hypothyroidism stable on hormone replacement or
             Sjorgen's syndrome will not be excluded from the study. Subjects that have adrenal or
             pituitary insufficiency that require physiologic corticosteroid replacement therapy
             would not be excluded from the study.

          -  Has evidence of interstitial lung disease or history of (non-infectious) pneumonitis
             that required steroids or current pneumonitis.

          -  Has an active infection requiring systemic therapy.

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator.

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment.

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
             anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including
             ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation
             or checkpoint pathways).

          -  Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

          -  Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected).

          -  Has received a live vaccine within 30 days prior to the first dose of trial treatment.

        Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
        are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated
        vaccines, and are not allowed.