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CompletedNCT01675765Updated Sep 30, 2020Results posted

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

A Phase 1 interventional study of Immunotherapy plus chemotherapy and Immunotherapy with cyclophosphamide plus chemotherapy in Malignant Pleural Mesothelioma, sponsored by Aduro Biotech, Inc.. Completed at 5 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-09-30.

Sponsored by Aduro Biotech, Inc. · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
60
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • 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
03

In context

Mesothelioma

470 studies on the registry are indexed under Mesothelioma; 75 are open to participants now.

This study's enrollment of 60 is above the median of 40 across 371 interventional studies indexed under Mesothelioma.

Browse Mesothelioma studies →

Lead sponsor

Aduro Biotech, Inc. is the lead sponsor of 8 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
60 participants (actual)

Study arms

  • Experimental
    Immunotherapy plus chemotherapy

    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

  • 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

Interventions

  • BiologicalImmunotherapy plus chemotherapy

    live attenuated double deleted Lm

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

  • BiologicalImmunotherapy with cyclophosphamide plus chemotherapy

    live attenuated double deleted Lm

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

06

What researchers measure

Primary outcomes

  1. Number of Subjects Reporting Adverse Events

    Count of subjects with incidences of adverse events.

    Time frame: From first study dose until 28 days after the final dose (an average of 44 weeks)

  2. 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)

Secondary outcomes

  1. Objective Tumor Response

    Objective tumor response was measured using modified Response Evaluation Criteria in Solid Tumors (mRECIST) for assessment of response in malignant pleural mesothelioma (MPM). Per mRECIST for target lesions and assessed by CT: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease, those who fulfilled the criteria for neither PR nor PD; Progressive Disease (PD), \>=20% increase in the sum of the longest diameter of target lesions.

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

  2. 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

  3. 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)

07

Results

Posted Sep 30, 2020

Participant flow

Participant flow — Overall Study
MilestoneImmunotherapy Plus ChemotherapyImmunotherapy With Cyclophosphamide Plus Chemotherapy
Started3822
Completed2714
Not completed118
Withdrew: Progressive disease44
Withdrew: Adverse event12
Withdrew: Withdrawal by subject20
Withdrew: Death10
Withdrew: Clinical progression32

Outcome measures

PrimaryNumber of Subjects Reporting Adverse Events

Count of subjects with incidences of adverse events.

Time frame:
From first study dose until 28 days after the final dose (an average of 44 weeks)
Reported as:
Count of participants · Participants
Number of Subjects Reporting Adverse Events
ParticipantsImmunotherapy Plus ChemotherapyImmunotherapy With Cyclophosphamide Plus Chemotherapy
Number of Subjects Reporting Adverse Events3822
PrimaryInduction 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)

No measurements were reported for this outcome.

SecondaryObjective Tumor Response

Objective tumor response was measured using modified Response Evaluation Criteria in Solid Tumors (mRECIST) for assessment of response in malignant pleural mesothelioma (MPM). Per mRECIST for target lesions and assessed by CT: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease, those who fulfilled the criteria for neither PR nor PD; Progressive Disease (PD), \>=20% increase in the sum of the longest diameter of target lesions.

Time frame:
Baseline to measured disease progression or death (up to 12 months or longer)
Reported as:
Count of participants · Participants
Objective Tumor Response
ParticipantsImmunotherapy Plus ChemotherapyImmunotherapy With Cyclophosphamide Plus Chemotherapy
Complete Response10
Partial Response1911
Stable Disease148
Progressive Disease12
Not Assessable10
SecondaryTime 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

No measurements were reported for this outcome.

SecondarySerum 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)

No measurements were reported for this outcome.

Adverse events

Collected over From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Immunotherapy Plus Chemotherapy3/38 (7.9%)15/38 (39.5%)38/38 (100%)
Immunotherapy With Cyclophosphamide Plus Chemotherapy0/22 (0%)11/22 (50%)22/22 (100%)
Most frequent serious events
Showing 10 of 28
Most frequent serious events
EventImmunotherapy Plus ChemotherapyImmunotherapy With Cyclophosphamide Plus Chemotherapy
PneumoniaInfections and infestations1/382/22
DyspnoeaRespiratory, thoracic and mediastinal disorders3/380/22
ConstipationGastrointestinal disorders2/381/22
NauseaGastrointestinal disorders2/380/22
VomitingGastrointestinal disorders2/380/22
Abdominal painGastrointestinal disorders0/381/22
Diverticular perforationGastrointestinal disorders0/381/22
Large intestine perforationGastrointestinal disorders0/381/22
HypoxiaRespiratory, thoracic and mediastinal disorders0/381/22
Pleuritic painRespiratory, thoracic and mediastinal disorders0/381/22
Most frequent other events
Showing 10 of 97
Most frequent other events
EventImmunotherapy Plus ChemotherapyImmunotherapy With Cyclophosphamide Plus Chemotherapy
ChillsGeneral disorders37/3822/22
PyrexiaGeneral disorders37/3821/22
NauseaGastrointestinal disorders31/3812/22
VomitingGastrointestinal disorders25/385/22
FatigueGeneral disorders23/3812/22
Decreased appetiteMetabolism and nutrition disorders19/384/22
ConstipationGastrointestinal disorders15/387/22
AnaemiaBlood and lymphatic system disorders15/388/22
Blood creatinine increasedInvestigations6/387/22
HeadacheNervous system disorders11/386/22

Baseline characteristics

Age, Customized
Age, Customized(Participants)Immunotherapy Plus ChemotherapyImmunotherapy With Cyclophosphamide Plus ChemotherapyTotal
<65 years9615
>=65 years291645
Sex: Female, Male
Sex: Female, Male(Participants)Immunotherapy Plus ChemotherapyImmunotherapy With Cyclophosphamide Plus ChemotherapyTotal
Female459
Male341751
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Immunotherapy Plus ChemotherapyImmunotherapy With Cyclophosphamide Plus ChemotherapyTotal
Hispanic or Latino101
Not Hispanic or Latino372259
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Immunotherapy Plus ChemotherapyImmunotherapy With Cyclophosphamide Plus ChemotherapyTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American202
White362258
More than one race000
Unknown or Not Reported000
Weight
Weight(kg)Immunotherapy Plus ChemotherapyImmunotherapy With Cyclophosphamide Plus ChemotherapyTotal
Mean81.63 ± 16.20373.83 ± 12.34078.77 ± 15.271
Height
Height(cm)Immunotherapy Plus ChemotherapyImmunotherapy With Cyclophosphamide Plus ChemotherapyTotal
Mean174.51 ± 8.295168.41 ± 7.102172.28 ± 8.359
Body Mass Index
Body Mass Index(kg/m^2)Immunotherapy Plus ChemotherapyImmunotherapy With Cyclophosphamide Plus ChemotherapyTotal
Mean26.702 ± 4.329226.076 ± 4.458426.473 ± 4.3498
Body Surface Area
Body Surface Area(m^2)Immunotherapy Plus ChemotherapyImmunotherapy With Cyclophosphamide Plus ChemotherapyTotal
Mean1.982 ± 0.22301.852 ± 0.17561.935 ± 0.2148
08

Study locations

5 sites
  • University of California at San Francisco
    San Francisco, California 94115, United States
  • H. Lee Moffitt Cancer Center
    Tampa, Florida 33612, United States
  • University of Chicago Medical Center
    Chicago, Illinois 60637, United States
  • National Cancer Institute
    Bethesda, Maryland 20892, United States
  • University of Pennsylvania Abramson Cancer Center
    Philadelphia, Pennsylvania 19104, United States
09

References and documents

Publications

  • 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. PubMed 22595054 ↗
  • 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. PubMed 31263030 ↗

Study documents

  • Study protocol · Mar 8, 2018
  • Statistical analysis plan · May 4, 2018

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 30, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01675765
Lead sponsor
Aduro Biotech, Inc.
Responsible party
Sponsor
First posted
Aug 30, 2012
Start date
Sep 3, 2014
Primary completion
Sep 5, 2018
Completion
Aug 19, 2019
Results posted
Sep 30, 2020
Last update
Sep 30, 2020

Study contacts

Raffit Hassan, MD
principal investigator · National Cancer Institute (NCI)

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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