Pembrolizumab and Paclitaxel in Refractory Small Cell Lung Cancer
Condition: Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma
Intervention: pembrolizumab, paclitaxel
Intervention description: pembrolizumab, paclitaxel
Intervention MeSH terms: Paclitaxel; Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: pembrolizumab; paclitaxel

Summary:

      Patients with refractory SCLC. Patients will be treated with paclitaxel and pembrolizumab.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Be willing and able to provide written informed consent/assent for the trial.

          2. Be 20 years of age on day of signing informed consent.

          3. Have measurable lesions based on RECIST 1.1.

          4. Have provided tissue from an archival tissue sample obtained after the last previous
             treatment or newly obtained core or excisional biopsy of a tumor lesion.

          5. Have a performance status of 0 or 1 on the ECOG Performance Scale.

          6. Demonstrate adequate organ function as defined below 'adequate organ fuction
             laboratory values', all screening labs should be performed within 10 days of treatment
             initiation.

             'adequate organ fuction laboratory values' System Laboratory Value Hematological
             Absolute neutrophil count (ANC) ≥ 1,500 /mcL Platelets ≥100,000 / mcL Hemoglobin ≥ 9
             g/dL or ≥ 5.6 mmol/L Renal Serum creatinine OR Measured or calculateda creatinine
             clearance (GFR can also be used in place of creatinine or CrCl)≤1.5 X upper limit of
             normal (ULN) OR ≥ 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.

          7. Female subject of childbearing potential should have a negative urine or serum
             pregnancy within 72 hours prior to receiving the first dose of study medication. If
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required.

          8. 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 (Reference
             Section 5.7.2). Subjects of childbearing potential are those who have not been
             surgically sterilized or have not been free from menses for > 1 year.

          9. 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:

          1. Is currently participating in or has participated in a study of an investigational
             agent or using an investigational device within 4 weeks of the first dose of
             treatment.

          2. 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.

          3. Has had a prior anti-cancer 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.

          4. Has had prior chemotherapy, targeted small molecule therapy, or radiation 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 are an exception to this criterion and
                  may qualify for the study.

               -  Note: If subject received major surgery, they must have recovered adequately from
                  the toxicity and/or complications from the intervention prior to starting
                  therapy.

          5. 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.

          6. Has known active central nervous system (CNS) 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 at least 7 days prior to trial treatment.

          7. Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

          8. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.

          9. Has an active infection requiring systemic therapy.

         10. 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.

         11. Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

         12. 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.

         13. 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).

         14. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

         15. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected). (inactive HBsAg carriers with prophylactic antiviral agent
             are allowed)

         16. Has received a live vaccine within 30 days prior to the first dose of trial treatment.

         17. Has a known history of active TB (Bacillus Tuberculosis)

         18. Has known hypersensitivity to MK-3475 or any of its excipients