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Safety and Efficacy of Listeria in Combination With Chemotherapy as Front-line Treatment for Malignant Pleural Mesothelioma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01675765
Recruitment Status : Completed
First Posted : August 30, 2012
Results First Posted : September 30, 2020
Last Update Posted : September 30, 2020
Sponsor:
Information provided by (Responsible Party):
Aduro Biotech, Inc.

Tracking Information
First Submitted Date  ICMJE August 23, 2012
First Posted Date  ICMJE August 30, 2012
Results First Submitted Date  ICMJE September 2, 2020
Results First Posted Date  ICMJE September 30, 2020
Last Update Posted Date September 30, 2020
Actual Study Start Date  ICMJE September 3, 2014
Actual Primary Completion Date September 5, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 28, 2020)
  • Number of Subjects Reporting Adverse Events [ Time Frame: From first study dose until 28 days after the final dose (an average of 44 weeks) ]
    Count of subjects with incidences of adverse events.
  • Induction of Immune Response to Mesothelin by Enzyme-linked Immunosorbent Spot (ELISPOT) Assay [ Time Frame: Change over time assessed at multiple time points until disease progression or death (up to 12 months or longer) ]
Original Primary Outcome Measures  ICMJE
 (submitted: August 28, 2012)
  • Number of Subjects Reporting Adverse Events [ Time Frame: From first study dose through duration of study (up to 30 weeks or longer) ]
  • Induction of Immune Response to Mesothelin by Enzyme-linked Immunosorbent Spot (ELISPOT) Assay [ Time Frame: Change over time assessed at multiple time points until disease progression or death (up to 12 months or longer) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 28, 2020)
  • Objective Tumor Response [ Time Frame: Baseline to measured disease progression or death (up to 12 months or longer) ]
    Objective tumor response was measured using modified Response Evaluation Criteria in Solid Tumors (mRECIST) for assessment of response in malignant pleural mesothelioma (MPM). Per mRECIST for target lesions and assessed by CT: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease, those who fulfilled the criteria for neither PR nor PD; Progressive Disease (PD), >=20% increase in the sum of the longest diameter of target lesions.
  • Time to Progression [ Time Frame: From date of randomization until date of documented progression (by modified RECIST or immune-related response criteria) or death, assessed up to 12 months or longer ]
  • Serum Mesothelin as Correlate of Therapeutic Response [ Time Frame: Change over time assessed at multiple time points until disease progression or death (up to 12 months or longer) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 28, 2012)
  • Objective Tumor Response [ Time Frame: Change over time assessed at multiple time points until disease progression or death (up to 12 months or longer) ]
  • Time to Progression [ Time Frame: From date of randomization until date of documented progression (by modified RECIST or immune-related response criteria) or death, assessed up to 12 months or longer ]
  • Serum Mesothelin as Correlate of Therapeutic Response [ Time Frame: Change over time assessed at multiple time points until disease progression or death (up to 12 months or longer) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Listeria in Combination With Chemotherapy as Front-line Treatment for Malignant Pleural Mesothelioma
Official Title  ICMJE A Phase 1B Study to Evaluate the Safety and Induction of Immune Response of CRS-207 in Combination With Pemetrexed and Cisplatin as Front-line Therapy in Adults With Malignant Pleural Mesothelioma
Brief 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.
Detailed Description

Up to 60 subjects will be enrolled in this study. Eligible subjects will receive 2 prime vaccinations of CRS-207 (1×10^9 colony-forming units [CFU] given intravenously [i.v.] over 2 hours) (with or without cyclophosphamide) 2 weeks apart followed 2 weeks later by up to 6 cycles of pemetrexed and cisplatin 21 days apart. Three weeks after completion of chemotherapy, subjects will receive an additional 2 infusions (boost vaccinations) of CRS-207 3 weeks apart. Subjects will be followed every 8 weeks until disease progression by immune-related response criteria. Subjects who continue to meet dosing eligibility may receive additional CRS-207 (with or without cyclophosphamide) infusions (maintenance vaccinations) at each follow-up visit.

Study assessments include blood draws for safety and immune response monitoring and CT scans [with optional fluorodeoxyglucose positron emission tomography (FDG-PET)] or magnetic resonance imaging (MRI) to monitor disease status. In addition, optional tumor biopsies may be performed before, during and after treatment.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Malignant Pleural Mesothelioma
Intervention  ICMJE
  • Biological: Immunotherapy plus chemotherapy
    live attenuated double deleted Lm
    Other Names:
    • CRS-207
    • Listeria
    • pemetrexed
    • cisplatin
    • ALIMTA
    • Platinol
  • Biological: Immunotherapy with cyclophosphamide plus chemotherapy
    live attenuated double deleted Lm
    Other Names:
    • CRS-207
    • Cytoxan
    • pemetrexed
    • cisplatin
    • ALIMTA
    • Platinol
    • Listeria
Study Arms  ICMJE
  • Experimental: Immunotherapy plus chemotherapy

    Weeks 1 and 3: CRS-207 (1 × 10^9 CFU)

    Weeks 5, 8, 11, 14, 17 and 20 (up to 6 cycles every 21 days): pemetrexed (500 mg/m^2) and cisplatin (75 mg/m^2)

    Weeks 23 and 26: CRS-207

    Maintenance Vaccinations: CRS-207 every 8 weeks (starting at Week 34) until disease progression

    Intervention: Biological: Immunotherapy plus chemotherapy
  • Experimental: Immunotherapy with cyclophosphamide plus chemotherapy

    Weeks 1 and 3: cyclophosphamide (200 mg/m^2), CRS-207 (1 × 10^9 CFU)

    Weeks 5, 8, 11, 14, 17 and 20 (up to 6 cycles every 21 days): pemetrexed (500 mg/m^2) and cisplatin (75 mg/m^2)

    Weeks 23 and 26: cyclophosphamide one day before CRS-207

    Maintenance Vaccinations: cyclophosphamide one day before CRS-207 every 8 weeks (starting at Week 34) until disease progression

    Intervention: Biological: Immunotherapy with cyclophosphamide plus chemotherapy
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 23, 2015)
60
Original Estimated Enrollment  ICMJE
 (submitted: August 28, 2012)
16
Actual Study Completion Date  ICMJE August 19, 2019
Actual Primary Completion Date September 5, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01675765
Other Study ID Numbers  ICMJE ADU-CL-02
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Aduro Biotech, Inc.
Study Sponsor  ICMJE Aduro Biotech, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Raffit Hassan, MD National Cancer Institute (NCI)
PRS Account Aduro Biotech, Inc.
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP