NCT01675765 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1
Status at capture: COMPLETED
Registry last update: 2020-09-30

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Subjects Reporting Adverse Events

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outcome · POSTED

Induction of Immune Response to Mesothelin by Enzyme-linked Immunosorbent Spot (ELISPOT) Assay

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outcome · POSTED

Objective Tumor Response

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outcome · POSTED

Time to Progression

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outcome · POSTED

Serum Mesothelin as Correlate of Therapeutic Response

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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
intervention Names
Biological: Immunotherapy plus chemotherapy
label
Immunotherapy plus chemotherapy
type
EXPERIMENTAL
description
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
intervention Names
Biological: Immunotherapy with cyclophosphamide plus chemotherapy
label
Immunotherapy with cyclophosphamide plus chemotherapy
type
EXPERIMENTAL

interventions

arm Group Labels
Immunotherapy plus chemotherapy
description
live attenuated double deleted Lm
name
Immunotherapy plus chemotherapy
other Names
CRS-207
Listeria
pemetrexed
cisplatin
ALIMTA
Platinol
type
BIOLOGICAL
arm Group Labels
Immunotherapy with cyclophosphamide plus chemotherapy
description
live attenuated double deleted Lm
name
Immunotherapy with cyclophosphamide plus chemotherapy
other Names
CRS-207
Cytoxan
pemetrexed
cisplatin
ALIMTA
Platinol
Listeria
type
BIOLOGICAL

Study design

allocation

NON_RANDOMIZED

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 60
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Count of subjects with incidences of adverse events.
measure
Number of Subjects Reporting Adverse Events
time Frame
From first study dose until 28 days after the final dose (an average of 44 weeks)
measure
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

description
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.
measure
Objective Tumor Response
time Frame
Baseline to measured disease progression or death (up to 12 months or longer)
measure
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
measure
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)

Full study description

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.
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.

Source references

references

citation
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
type
BACKGROUND
citation
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
type
DERIVED

Source notices and limitations

Discovery and provenance

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Preserved source evidence · Not medical advice