MK-3475 as Maintenance Therapy in Extensive Stage SCLC
Condition: Extensive Stage Small Cell Lung Carcinoma
MeSH terms: Small Cell Lung Carcinoma
Intervention: Pembrolizumab; Laboratory Biomarker Analysis
Intervention description: Given IV; Correlative studies
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well pembrolizumab works in treating patients with extensive
      stage small cell lung cancer after completion of combination chemotherapy. Pembrolizumab may
      be effective in controlling small cell lung cancer for a longer period of time in patients
      with responsive or stable disease after completion of combination chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with extensive stage SCLC who have completed at least 4 cycles of platinum
             (carboplatin/cisplatin) and etoposide chemotherapy as their first line therapy and
             have responding or stable disease to this therapy are eligible for this study;
             patients who received platinum/etoposide previously for SCLC and it was repeated for
             recurrence will not be eligible

          -  Patients should be willing and able to provide written informed consent for the trial

          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             performance scale

          -  Demonstrate adequate organ function, all screening laboratories (labs) should be
             performed within 14 days of treatment initiation

          -  Absolute neutrophil count (ANC) >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Hemoglobin >= 9 g/dL or >= 5.6 mmol/L

          -  Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated*
             creatinine clearance >= 45 mL/min for subject with creatinine levels > 1.5 X
             institutional ULN; glomerular filtration rate (GFR) can also be used in place of
             creatinine or creatinine clearance [CrCl])

               -  Creatinine clearance should be calculated per institutional standard

          -  Serum total bilirubin =< 1.5 X ULN OR directed bilirubin =< ULN for subjects with
             total bilirubin levels > 1.5 ULN

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X
             ULN OR =< 5 X ULN for subjects with liver metastases

          -  Female subject of childbearing potential should have a negative urine or serum
             pregnancy within 1 week 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

          -  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 from 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 within 4 weeks of the first dose of treatment

          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy greater
             than 10 mg/day or any other form of immunosuppressive therapy within 7 days prior to
             the first dose of trial treatment

          -  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, or definitive 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; patients
             who received palliative radiation to any site or prophylactic cranial radiation (=< 30
             Gray [Gy]) or thoracic RT can start therapy with the study drug 7 days after the last
             day of radiation therapy as long as they have recovered from any adverse effects
             (i.e., =< grade 1 or at baseline) of such radiation therapy

               -  Note: subjects with =< grade 2 neuropathy or adverse events that are not
                  considered clinically meaningful such as alopecia 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

          -  Has a known additional malignancy that is progressing or requires active treatment;
             patient will be eligible if other malignancy is controlled and the treating physician
             determines that the patient's outcome is unlikely to be affected by the other tumor

          -  Has symptomatic central nervous system (CNS) metastases and/or carcinomatous
             meningitis; subjects with previously treated brain metastases may participate provided
             they are clinically stable and any neurologic symptoms have returned to baseline, have
             no clinical evidence of new or enlarging brain metastases, and are not using steroids
             greater than prednisone 10mg/day or equivalent dose of another steroid" prior to start
             of trial treatment

          -  Has an active autoimmune disease, including a paraneoplastic syndrome of autoimmune
             nature, requiring systemic treatment other than chemotherapy for SCLC, within the past
             3 months or a documented history of clinically severe autoimmune disease, or a
             syndrome that requires or required 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

          -  Has evidence of active, non-infectious 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-programmed cell death-1 (PD-1), anti-PD-L1,
             anti-PD-L2, anti-cluster of differentiation (CD)137, 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., hepatitis B virus surface antigen [HBsAg]
             reactive) or hepatitis C (e.g., hepatitis C [HCV] ribonucleic acid [RNA] [qualitative]
             is detected)

          -  Has received a live vaccine within 30 days prior to the first dose of trial treatment