Clinical trial: Nivolumab and Ipilimumab +/- UV1 Vaccination as Second Line Treatment in Patients With Malignant Mesothelioma (NCT04300244)

Eligibility criteria:
Inclusion Criteria:

          -  Histologically and/or cytologically confirmed malignant pleural mesothelioma.

          -  Unresectable disease

          -  Measurable disease, defined as at least 1 lesion (measurable) that can be accurately
             assessed at baseline by computed tomography (CT) or magnetic resonance imaging (MRI)
             and is suitable for repeated assessment (modified RECIST).

          -  Available unstained archived tumor tissue sample in sufficient quantity to allow for
             analyses. At least fifteen unstained slides or a tumor block (preferred). NOTE: A fine
             needle aspiration sample is not sufficient to make the patient eligible for
             enrollment. Given the complexity of mesothelioma pathological diagnosis , it is
             expected that they will have a core needle biopsy or surgical tumor biopsy as part of
             their initial diagnostic work up.

          -  Age ≥ 18 years.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.

          -  Willing to provide archived tumor tissue and blood samples for research.

          -  Adequate organ function as defined below

               1. Haemoglobin ≥ 9.0 g/dL

               2. Absolute neutrophil count (ANC) 1.5 (or 1.0) x (> 1500 per mm3)

               3. Platelet count ≥100 (or 75) x 109/L (>75,000 per mm3)

               4. Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN).

               5. AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver
                  metastases are present, in which case it must be ≤5x ULN

               6. Measured creatinine clearance (CL)

                    1. >40 mL/min

                    2. Calculated creatinine CL>40 mL/min (Cockcroft-Gault formula)

                    3. 24-hour urinecollection for determination of CL

          -  Males: Creatinine CL (mL/min) =Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)

          -  Females:Creatinine CL (mL/min)=Weight (kg) x (140 - Age)x0.85 72 x serum creatinine
             (mg/dL)

          -  Previously treated with at least one line of platinum -pemetrexed

        Exclusion Criteria:

          -  Disease suitable for curative surgery

          -  Previous treatment with a PD-1 or PD-L1 inhibitor, including nivolumab or any other
             agent targeting immune checkpoints.

          -  Non-pleural mesothelioma e.g. mesothelioma arising in peritoneum, tunica vaginalis or
             any serosal surface other than the pleura.

          -  Active second malignancy other than non-melanoma skin cancer or cervical carcinoma in
             situ.

          -  Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive
             of but not limited to surgery, radiation and/or corticosteroids (prednisone >10 mg or
             equivalent). Surgery, radiation and/or corticosteroids (any dose >10 mg prednisone
             equivalent) must have been completed ≥ 2 weeks prior to registration.

          -  Uncontrolled seizures.

          -  Current or prior use of immunosuppressive medication within 28 days before the first
             dose of nivolumab, with the exceptions of intranasal and inhaled corticosteroids or
             systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of
             prednisone, or an equivalent corticosteroid. Standard steroid premedication given
             prior to chemotherapy or as prophylaxis for imaging contrast allergy should not be
             counted for this criterion.

          -  Active or prior documented autoimmune or inflammatory disorders (including
             inflammatory bowel disease, diverticulitis with the exception of diverticulosis,
             celiac disease, irritable bowel disease; Wegner syndrome) within the past 2 years.
             Subjects with vitiligo, alopecia, Grave's disease, or psoriasis not requiring systemic
             treatment (within the past 3 years) are not excluded.

          -  History of primary immunodeficiency.

          -  History of allogeneic organ transplant.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
             angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active
             bleeding diatheses including any subject known to have psychiatric illness/social
             situations that would limit compliance with study requirements or compromise the
             ability of the subject to give written informed consent.

          -  Active infection including tuberculosis (clinical evaluation including: physical
             examination findings, radiographic findings, positive PPD test, etc.), hepatitis B
             (known positive HBV surface antigen [HBsAg] result), hepatitis C, or human
             immunodeficiency virus (positive HIV 1/2 antibodies as defined by a positive ELISA
             test). Patients with a past or resolved HBV infection (defined as the presence of
             hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients
             positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction
             is negative for HCV RNA. HIV testing is not required in the absence of clinical
             suspicion.

          -  Known history of leptomeningeal carcinomatosis.

          -  Pregnant or lactating women

          -  Live attenuated vaccination within 30 days prior to study entry or within 30 days of
             receiving nivolumab.

          -  Any condition that, in the opinion of the investigator, would interfere with the
             evaluation of study treatment or interpretation of patient safety or study results.

          -  History of allergy or hypersensitivity to any of the active substances or excipients
             in the study drug.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.


Patient description (medical language): A 61-year-old man comes to the clinic due to nonproductive cough and progressive dyspnea.  The patient's medical conditions include hypertension, hypercholesteremia and peptic ulcer disease.  He smokes 2 packs of cigarettes daily for the past 30 years.  On examination, there are decreased breath sounds and percussive dullness at the base of the left lung.  Other vital signs are normal. Abdomen is soft without tenderness. CT scan shows a left-sided pleural effusion and nodular thickening of the pleura. The plural fluid was bloody on thoracentesis. Biopsy shows proliferation of epithelioid-type cells with very long microvilli.

Patient description (patient's own words): I am 61 and I had to go to the clinic because I couldn't stop coughing and I experienced some breath shortness. I suffer from hypertension and cholesterol and I also have a stomach ulcer. I should admit that I've been smoking 2 packs of cigarettes every day for the past 30 years. My doctor told me that my breath in my left lung sounds bad. But he told me that my blood pressure, heart rate, breathing rate and temperature are normal. My belly is also normal. However my X-Rays show some liquid on the left side and a mass where the liquid got hard. The scary thing is that the liquid was bloody when they got it out. They did a biopsy and it showed that I have an increase of epithelioid-type cells with very long microvilli.

Does the patient match the trial criteria? Contradiction