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

NCT01675765 | Completed Phase 1 Results

• 1 other identifier: ADU-CL-02
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Malignant Pleural Mesothelioma

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Number of Subjects Reporting Adverse Events

  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

  Change over time assessed at multiple time points until disease progression or death (up to 12 months or longer)

Secondary Outcomes (3)

• Objective Tumor Response

  Baseline to measured disease progression or death (up to 12 months or longer)

• Time to Progression

  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

  Change over time assessed at multiple time points until disease progression or death (up to 12 months or longer)

Study Arms (2)

Immunotherapy plus chemotherapy

EXPERIMENTAL

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

Immunotherapy with cyclophosphamide plus chemotherapy

EXPERIMENTAL

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

Interventions

Immunotherapy plus chemotherapy BIOLOGICAL

live attenuated double deleted Lm

Also known as: CRS-207, Listeria, pemetrexed, cisplatin, ALIMTA, Platinol

Immunotherapy plus chemotherapy

Immunotherapy with cyclophosphamide plus chemotherapy BIOLOGICAL

live attenuated double deleted Lm

Also known as: CRS-207, Cytoxan, pemetrexed, cisplatin, ALIMTA, Platinol, Listeria

Immunotherapy with cyclophosphamide plus chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Aduro Biotech, Inc.: lead

Study Sites (5)

University of California at San Francisco

San Francisco, California, 94115, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

National Cancer Institute

Bethesda, Maryland, 20892, United States

Location

University of Pennsylvania Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (2)

• Le DT, Dubenksy TW Jr, Brockstedt DG. Clinical development of Listeria monocytogenes-based immunotherapies. Semin Oncol. 2012 Jun;39(3):311-22. doi: 10.1053/j.seminoncol.2012.02.008.

  PMID: 22595054 BACKGROUND

• Hassan R, Alley E, Kindler H, Antonia S, Jahan T, Honarmand S, Nair N, Whiting CC, Enstrom A, Lemmens E, Tsujikawa T, Kumar S, Choe G, Thomas A, McDougall K, Murphy AL, Jaffee E, Coussens LM, Brockstedt DG. Clinical Response of Live-Attenuated, Listeria monocytogenes Expressing Mesothelin (CRS-207) with Chemotherapy in Patients with Malignant Pleural Mesothelioma. Clin Cancer Res. 2019 Oct 1;25(19):5787-5798. doi: 10.1158/1078-0432.CCR-19-0070. Epub 2019 Jul 1.

  PMID: 31263030 DERIVED

MeSH Terms

Conditions

Mesothelioma, Malignant; Neoplasms

Interventions

Immunotherapy; Drug Therapy; Pemetrexed; Cisplatin; Cyclophosphamide

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Immunomodulation; Biological Therapy; Therapeutics; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Corporate Communications
• Organization: Aduro Biotech, Inc.

press@aduro.com

510-848-4400

Study Officials

• Raffit Hassan, MD

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2012
• First Posted: August 30, 2012
• Study Start: September 3, 2014
• Primary Completion: September 5, 2018
• Study Completion: August 19, 2019
• Last Updated: September 30, 2020
• Results First Posted: September 30, 2020

Record last verified: 2020-09

Locations

US (5)