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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

Phase 1
18 Years
Open (Enrolling)
Malignant Pleural Mesothelioma

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Trial Information

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

Up to 16 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) 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 infusions
(maintenance vaccinations) every 16 weeks.

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.

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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of subjects reporting adverse events

Outcome Time Frame:

From first study dose through duration of study (up to 30 weeks or longer)

Safety Issue:


Principal Investigator

Raffit Hassan, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Food and Drug Administration

Study ID:




Start Date:

August 2012

Completion Date:

June 2014

Related Keywords:

  • Malignant Pleural Mesothelioma
  • 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
  • Mesothelioma



H. Lee Moffitt Cancer CenterTampa, Florida  33612
University of Chicago Medical CenterChicago, Illinois  60637
University of Pennsylvania Abramson Cancer CenterPhiladelphia, Pennsylvania  19104
National Cancer InstituteBethesda, Maryland  20892-1922