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

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase IBiomarker/Laboratory analysis, Treatment18 and overADU-CL-02
NCI-2012-03035, NCT01675765

Trial Description

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.

Further Study Information

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.

Eligibility Criteria

Inclusion Criteria:

Have adequate organ function as defined by specified laboratory values

Be willing and able to give written informed consent, and be able to comply with all

study procedures

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.)

Have an anticipated life expectancy of greater than 6 months

Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Be at least 18 years of age

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)

Exclusion Criteria:

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

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

Be a woman who is pregnant or breastfeeding

Any immunodeficiency disease or immunocompromised state or active autoimmune disease

or history of autoimmune disease requiring systemic steroids or other

immunosuppressive treatment

Infection with HIV or hepatitis B or C at screening

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)

Use more than 3 g/d of acetaminophen

Used any systemic steroids within 28 days of study treatment

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

Have clinically significant and/or malignant pleural effusion

Have any evidence of hepatic cirrhosis or clinical or radiographic ascites

Documented and ongoing brain metastases

Currently have or have history of certain study-specified heart, liver, kidney, lung,

neurological, immune or other medical conditions

Prior systemic chemotherapy

Treatment with an investigational agent within 4 weeks before dosing

Prior radiotherapy or biologic therapy

Surgery within 2 weeks prior to dosing

A candidate for curative surgery

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

Aduro BioTech Inc

    Trial Sites

    U.S.A.

    California
    San Francisco

    UCSF Medical Center-Mount Zion

    Thierry Marie Jahan
    Principal Investigator

    Illinois
    Chicago

    University of Chicago Comprehensive Cancer Center

    Hedy Lee Kindler
    Principal Investigator

    Maryland
    Bethesda

    Mark O Hatfield-Warren Grant Magnuson Clinical Center

    Raffit Hassan
    Principal Investigator

    Pennsylvania
    Philadelphia

    University of Pennsylvania/Abramson Cancer Center

    Evan W. Alley
    Principal Investigator

    Link to the current ClinicalTrials.gov record.
    NLM Identifer NCT01675765

    Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.