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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Aduro Biotech, Inc.
ClinicalTrials.gov Identifier:
NCT01675765
First received: August 23, 2012
Last updated: June 16, 2016
Last verified: June 2016
  Purpose
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.

Condition Intervention Phase
Malignant Pleural Mesothelioma
Biological: Immunotherapy plus chemotherapy
Biological: Immunotherapy with cyclophosphamide plus chemotherapy
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Aduro Biotech, Inc.:

Primary Outcome Measures:
  • Number of subjects reporting adverse events [ Time Frame: From first study dose through duration of study (up to 30 weeks or longer) ] [ Designated as safety issue: Yes ]
  • 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) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective tumor response [ Time Frame: Change over time assessed at multiple time points until disease progression or death (up to 12 months or longer) ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: August 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Immunotherapy plus chemotherapy- CLOSED to enrollment

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:
  • CRS-207
  • Listeria
  • pemetrexed
  • cisplatin
  • ALIMTA
  • Platinol
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:
  • CRS-207
  • Cytoxan
  • pemetrexed
  • cisplatin
  • ALIMTA
  • Platinol
  • Listeria

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01675765

Locations
United States, California
University of California at San Francisco
San Francisco, California, United States, 94115
United States, Florida
H. Lee Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Illinois
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
United States, Maryland
National Cancer Institute
Bethesda, Maryland, United States, 20892
United States, Pennsylvania
University of Pennsylvania Abramson Cancer Center
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Aduro Biotech, Inc.
Investigators
Principal Investigator: Raffit Hassan, MD National Cancer Institute (NCI)
  More Information

Publications:
Responsible Party: Aduro Biotech, Inc.
ClinicalTrials.gov Identifier: NCT01675765     History of Changes
Other Study ID Numbers: ADU-CL-02 
Study First Received: August 23, 2012
Last Updated: June 16, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Aduro Biotech, Inc.:
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

Additional relevant MeSH terms:
Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Cisplatin
Cyclophosphamide
Pemetrexed
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on December 09, 2016