Malignant Pleural MesotheliomaPhase 1NCT01675765
Safety and Efficacy of Listeria in Combination With Chemotherapy as Front-line Treatment for Malignant Pleural Mesothelioma
A Phase 1 study testing Immunotherapy plus chemotherapy and Immunotherapy with cyclophosphamide plus chemotherapy in people with Malignant Pleural Mesothelioma, run by Aduro Biotech, Inc. at 5 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Pleural Mesothelioma
- What is being tested?
- Immunotherapy plus chemotherapy and Immunotherapy with cyclophosphamide plus chemotherapy
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 5 sitesUnited States
- Study dates
- 3 Sep 2014to 19 Aug 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
National Cancer Institute
Bethesda, Maryland, 20892
University of Chicago Medical Center
Chicago, Illinois, 60637
University of Pennsylvania Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
University of California at San Francisco
San Francisco, California, 94115
H. Lee Moffitt Cancer Center
Tampa, Florida, 33612
About this study
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
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.
- Conditions
- Malignant Pleural Mesothelioma
- Being tested
- Immunotherapy plus chemotherapy, Immunotherapy with cyclophosphamide plus chemotherapy
- 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
- Medical subject headings
- Mesothelioma, Malignant, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Immunotherapy plus chemotherapyBiological
Also called CRS-207, Listeria, pemetrexed, cisplatin
live attenuated double deleted Lm
Immunotherapy with cyclophosphamide plus chemotherapyBiological
Also called CRS-207, Cytoxan, pemetrexed, cisplatin
live attenuated double deleted Lm
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Biological: Immunotherapy with cyclophosphamide plus chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects Reporting Adverse Events
Count of subjects with incidences of adverse events.
Measured: 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
Measured: 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
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.
Measured: Baseline to measured disease progression or death (up to 12 months or longer)
Time to Progression
Measured: 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
Measured: Change over time assessed at multiple time points until disease progression or death (up to 12 months or longer)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2012 (estimated)
- Study start3 Sep 2014
- Primary completion5 Sep 2018
- Study completion19 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Malignant Pleural MesotheliomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aduro Biotech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Raffit Hassan, MD, Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01675765
- Sponsor's protocol ID
- ADU-CL-02
- Status last verified
- Sep 2020
- First submitted
- 23 Aug 2012
- Last updated
- 30 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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 22595054Hassan 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 at a glance
From the registry record, last updated by the sponsor on 30 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01675765
- Acronym / sponsor ID
- ADU-CL-02
- Conditions
- Malignant Pleural Mesothelioma
- Keywords
- Cancer, Cancer vaccine, Listeria monocytogenes, Listeria-based vaccines, Pemetrexed, Cisplatin, T regulatory cells, Mesothelin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Aduro Biotech, Inc.Industry (pharma, biotech, devices)
- Study start
- 3 Sep 2014 (actual)
- Primary completion
- 5 Sep 2018 (actual)
- Study completion
- 19 Aug 2019 (actual)
- First posted
- 30 Aug 2012 (estimated)
- Results
- Posted 30 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Immunotherapy plus chemotherapy | Experimental | Biological: Immunotherapy plus chemotherapyWeeks 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 |
| Immunotherapy with cyclophosphamide plus chemotherapy | Experimental | Biological: Immunotherapy with cyclophosphamide plus chemotherapyWeeks 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.)
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Immunotherapy plus chemotherapyAlso: CRS-207, Listeria, pemetrexed, cisplatinlive attenuated double deleted Lm | Biological | Immunotherapy plus chemotherapy |
| Immunotherapy with cyclophosphamide plus chemotherapyAlso: CRS-207, Cytoxan, pemetrexed, cisplatinlive attenuated double deleted Lm | Biological | Immunotherapy with cyclophosphamide plus chemotherapy |
Primary outcome
Number of Subjects Reporting Adverse Events
Time frame: From first study dose until 28 days after the final dose (an average of 44 weeks)
Count of subjects with incidences of adverse events.
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)
3 secondary outcomes
Objective Tumor Response
Time frame: Baseline to measured disease progression or death (up to 12 months or longer)
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
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22595054Le 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.
- Derived from this study: PubMed 31263030Hassan 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raffit Hassan, MD principal investigator
National Cancer Institute (NCI)
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Immunotherapy plus chemotherapy and Immunotherapy with cyclophosphamide plus chemotherapy in people with Malignant Pleural Mesothelioma, run by Aduro Biotech, Inc. at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01675765, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2020.