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

September 28, 2020 updated by: Aduro Biotech, Inc.

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94115
        • University of California at San Francisco
    • Florida
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Medical Center
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Cancer Institute
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania Abramson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
Biological: Immunotherapy plus chemotherapy
live attenuated double deleted Lm
Other Names:
  • ALIMTA
  • Platinol
  • cisplatin
  • pemetrexed
  • CRS-207
  • Listeria
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
Biological: Immunotherapy with cyclophosphamide plus chemotherapy
live attenuated double deleted Lm
Other Names:
  • Cytoxan
  • ALIMTA
  • Platinol
  • cisplatin
  • pemetrexed
  • CRS-207
  • Listeria

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
From first study dose until 28 days after the final dose (an average of 44 weeks)
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 over time assessed at multiple time points until disease progression or death (up to 12 months or longer)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Baseline to measured 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
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)
Change over time assessed at multiple time points until disease progression or death (up to 12 months or longer)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Aduro Biotech, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Raffit Hassan, MD, National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 3, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 5, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 19, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 23, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 28, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 30, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 30, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 28, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ADU-CL-02

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Malignant Pleural Mesothelioma

Clinical Trials on Immunotherapy plus chemotherapy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings