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

Official Title:

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

Basic Trial Information

Phase Type Age Sponsor Protocol IDs Status
Phase 1 Interventional 18 Years and older Aduro Biotech, Inc. ADU-CL-02
NCT01675765
Ongoing but not enrolling patients

Study Design:


Principal Investigator

Professor of Medicine
Chair, Data and Safety Monitoring Committee
Bonnie J. and Anthony Addario Endowed Chair in Thoracic Oncology
UCSF Helen Diller Family Comprehensive Cancer Center

Clinical Research Coordinator

UCSF Helen Diller Family Comprehensive Cancer Center
(415) 885-3673 Phone
415-353-9721 Fax

Trial 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

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

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.

Important

Final eligibility is determined by the health professionals conducting the trial and the protocol approved by the Committee on Human Resources (CHR) at the University of California, San Francisco (UCSF). The Patient Consent Form for this trial is available upon request. For more information about this trial, please see the full posting at ClinicalTrials.gov.

Information about this trial was obtained from the NIH Clinical Trials website, http://clinicaltrials.gov on 1/26/2017. UCSF specific information including the PI (Principal Investigator), trial enrollment status, and UCSF Study ID, supplement the ClinicalTrials.gov study posting.
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