Response to Pembrolizumab in Metastatic Melanoma: Computed Tomography Texture Analysis as a Predictive Biomarker
Condition: Metastatic Melanoma
MeSH terms: Melanoma
Intervention: Pembrolizumab; CT Scan
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Studies have shown that the study drug, pembrolizumab, works by helping the immune system. In
      this way, pembrolizumab may help to slow the growth of melanoma or may cause cancer cells to
      die. Compared to standard treatments, pembrolizumab seems to lengthen the time patients lived
      overall and the time without their cancer getting worse.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed melanoma that is recurrent/metastatic and not amenable to
             potentially curative surgery.

          -  Presence of clinically and/or radiologically documented disease based on RECIST 1.1.
             At least one site of disease must be unidimensionally measurable by contrast-enhanced
             CT scan as follows:

        CT scan (with slice thickness of ≤ 5 mm) ≥ 10 mm --> longest diameter Lymph nodes by CT
        scan ≥ 15 mm --> measured in short axis

          -  Age ≥ 18 years.

          -  ECOG Performance Status of 0 to 1.

          -  Previous Therapy

        Surgery:

        Previous surgery is permitted provided that it has been at least 21 days prior to patient
        registration and that wound healing has occurred.

        Systemic Therapy:

        Patients may not have received any prior systemic therapy for metastatic melanoma.

        Radiation:

        Palliative radiation is permitted provided > 7 days has elapsed between last dose and
        enrollment on the trial.

          -  Laboratory Requirements Absolute neutrophils ≥ 1.5 x 10^9/L Platelets ≥ 100 x 10^9/L
             Hemoglobin ≥ 90 g/L or ≥ 5.6 mmol/L (without transfusion or EPO dependency) Serum
             creatinine or measured or calculated creatinine: ≤1.5 x ULN or ≥ 60 mL/min for subject
             with creatinine clearance levels > 1.5 x ULN Serum Total Bilirubin ≤ 1.5 x ULN or
             Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 x ULN AST and
             ALT ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver mets) Albumin ≥ 25 g/L

          -  Women/men of childbearing potential must have agreed to use a highly effective
             contraceptive method.

          -  Women of childbearing potential will have a serum or urine pregnancy test within 7
             days prior to registration to determine eligibility.

          -  Patient consent must be obtained according to local Institutional and/or University
             Human Experimental Committee requirements.

          -  Patients must be accessible for treatment and follow up. Patients registered on this
             trial must be treated and followed at the participating centre.

        Exclusion Criteria:

          -  Patients who have received prior systemic treatment for metastatic melanoma.

          -  Patients with known history of Human Immunodeficiency Virus (HIV) (HIV 1/2
             antibodies).

          -  Patients with a known history of or known positive for Hepatitis B (HBsAg reactive) or
             Hepatitis C (HCV RNA [qualitative] is detected). Patients with unknown history of
             Hepatitis B virus (HBV) or Hepatitis C virus (HCV) will require screening.

          -  Patients with previously treated brain metastases may participate provided they are
             stable with no evidence of enlargement following radiation treatment and no acute
             radiation toxicity OR no evidence of enlargement at least 4 weeks prior to the first
             dose of study drug if untreated and are off systemic steroids for at least two weeks.

          -  Patients who are pregnant or breastfeeding, or expecting to conceive or father
             children within the projected duration of the study, starting with the pre-screening
             or screening visit through 4 months after the last dose of trial treatment.

          -  Patients who previously had a severe hypersensitivity reaction to treatment with
             another mAb.

          -  Patients with an active autoimmune disease or a documented history of autoimmune
             disease or syndrome that requires systemic steroids or immunosuppressive agents. (Only
             patients on active treatment are ineligible).

          -  Patients with a history of a malignancy (other than the disease under treatment in the
             study) within 5 years prior to first study drug administration.

          -  Patients on any systemic corticosteroid therapy within one week before the planned
             date for first dose of treatment or on any other form of immunosuppressive medication.

          -  Patients with an allergy to iodinated contrast media used for CT.

          -  Patients with a known history of active TB (Bacillus Tuberculosis).

          -  Patients with evidence of interstitial lung disease;

          -  Patients with known history of, or any evidence of active, non-infectious pneumonitis