Safety and Efficacy of Listeria in Combination With Chemotherapy as Front-line Treatment for Malignant Pleural Mesothelioma
Condition: Malignant Pleural Mesothelioma
MeSH terms: Mesothelioma; Mesothelioma, Malignant
Intervention: Immunotherapy plus chemotherapy; Immunotherapy with cyclophosphamide plus chemotherapy
Intervention description: live attenuated double deleted Lm; live attenuated double deleted Lm
Intervention MeSH terms: Cyclophosphamide; Cisplatin; Pemetrexed; Immunologic Factors; Immunomodulating Agents
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cancer; Cancer vaccine; Listeria monocytogenes; Listeria-based vaccines; Pemetrexed; Cisplatin; T regulatory cells; Mesothelin; Malignant Pleural Mesothelioma; Chemotherapy; Standard of care; Naive; Front-line; Immunotherapy; MPM

Summary:

      This clinical trial will evaluate the safety and immune response of the sequential
      administration cancer vaccine CRS-207 (with or without cyclophosphamide) followed by standard
      of care chemotherapy (pemetrexed and cisplatin). CRS-207 is a weakened (attenuated) form of
      Listeria monocytogenes that has been genetically-modified to reduce its capacity to cause
      disease, while maintaining its ability to stimulate potent immune responses. CRS-207 has been
      engineered to elicit an immune response against the tumor-associated antigen mesothelin,
      which has been shown to be present at higher levels on certain tumor cells (such as
      mesothelioma) than on normal cells. Pemetrexed and cisplatin are the standard chemotherapy
      regimen to treat malignant pleural mesothelioma. This trial will evaluate whether giving
      CRS-207 cancer vaccine with chemotherapy will induce anti-tumor immune responses and/or
      objective tumor response.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have histologically confirmed epithelial or biphasic MPM not amenable to potentially
             curative surgical resection (subjects with biphasic tumors that have a predominantly
             (≥50%) sarcomatoid component will be excluded)

          -  Be at least 18 years of age

          -  Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Have an anticipated life expectancy of greater than 6 months

          -  For women and men of childbearing potential, a medically acceptable method of highly
             effective contraception (oral hormonal contraceptive, condom plus spermicide, or
             hormone implants) must be used throughout the study period and for 28 days after their
             final vaccine administration. (A barrier method of contraception must be employed by
             all subjects [male and female], regardless of other methods.)

          -  Be willing and able to give written informed consent, and be able to comply with all
             study procedures

          -  Have adequate organ function as defined by specified laboratory values

        Exclusion Criteria:

          -  A candidate for curative surgery

          -  Surgery within 2 weeks prior to dosing

          -  Prior radiotherapy or biologic therapy

          -  Treatment with an investigational agent within 4 weeks before dosing

          -  Prior systemic chemotherapy

          -  Currently have or have history of certain study-specified heart, liver, kidney, lung,
             neurological, immune or other medical conditions

          -  Documented and ongoing brain metastases

          -  Have any evidence of hepatic cirrhosis or clinical or radiographic ascites

          -  Have clinically significant and/or malignant pleural effusion

          -  Known or suspected allergy or hypersensitivity to yeast or any other component of
             CRS-207 (e.g., glycerol), Platinol or platinum-containing compounds, or pemetrexed

          -  Used any systemic steroids within 28 days of study treatment

          -  Use more than 3 g/d of acetaminophen

          -  An artificial (prosthetic) joint or other artificial implant or device that cannot be
             easily removed (with some exceptions for dental and breast implants and biliary stents
             and mediports)

          -  Infection with HIV or hepatitis B or C at screening

          -  Any immunodeficiency disease or immunocompromised state or active autoimmune disease
             or history of autoimmune disease requiring systemic steroids or other
             immunosuppressive treatment

          -  Be a woman who is pregnant or breastfeeding

          -  Unable to avoid close contact with another individual known to be at high risk of
             listeriosis (e.g., newborn infant, pregnant woman, HIV-positive individual) during the
             course of CRS-207 treatment until completion of antibiotic regimen

          -  Conditions, including alcohol or drug dependence, intercurrent illness, or lack of
             sufficient peripheral venous access, that would affect the patient's ability to comply
             with study visits and procedures