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Trial record 1 of 3 for:    CRS-207 | mesothelioma
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Evaluation of CRS-207 With Pembrolizumab in Previously Treated Malignant Pleural Mesothelioma (MPM)

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ClinicalTrials.gov Identifier: NCT03175172
Recruitment Status : Terminated (Study was stopped due to low enrollment and lack of clinical activity.)
First Posted : June 5, 2017
Results First Posted : February 19, 2019
Last Update Posted : April 4, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Aduro Biotech, Inc.

Tracking Information
First Submitted Date  ICMJE June 1, 2017
First Posted Date  ICMJE June 5, 2017
Results First Submitted Date  ICMJE January 26, 2019
Results First Posted Date  ICMJE February 19, 2019
Last Update Posted Date April 4, 2019
Actual Study Start Date  ICMJE May 31, 2017
Actual Primary Completion Date January 9, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 26, 2019)
Overall Response Rate (ORR) [ Time Frame: BOR was assessed from the first dose of study treatment until documented disease progression, initiation of new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks. ]
ORR was evaluated based upon the best overall response (BOR) for individual study subjects. BOR was determined by the highest post-baseline qualitative response value for each assessed subject as measured by modified response evaluation criteria in solid tumors (modified RECIST) for MPM (Byrne and Nowak, 2004) and given the following hierarchy of overall response results: complete response (CR) > partial response (PR) > stable disease (SD) > progressive disease (PD) > not evaluable (NE). The protocol-specified ORR was defined as the percentage of evaluable subjects with a BOR of CR or PR; however, this percentage was not calculated per the final study Statistical Analysis Plan (SAP). Therefore, the number of evaluable subjects with BOR RECIST v1.1 values of CR, PR, SD, PD, and NE are provided for this outcome measure.
Original Primary Outcome Measures  ICMJE
 (submitted: June 2, 2017)
Objective Response Rate [ Time Frame: Through study completion, an average of 18 months ]
Defined as the proportion of subjects with complete response (CR) or partial response (PR); Modified RECIST (Response Evaluation Criteria in Solid Tumors) for MPM (Byrne and Nowak, 2004) will be used to assess tumor response and progression.
Change History Complete list of historical versions of study NCT03175172 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 22, 2019)
  • Disease Control Rate (DCR) [ Time Frame: BOR was assessed from the first dose of study treatment until documented disease progression, initiation of new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks. ]
    The percentage of evaluable subjects who exhibited a post-baseline tumor assessment BOR rating of CR, PR, or SD per modified RECIST for MPM.
  • Progression-Free Survival (PFS) [ Time Frame: Subjects followed for disease progression from first dose of study treatment until documented disease progression, initiation of new cancer treatment, death, or study termination, whichever is earlier, assessed up to 9 weeks. ]
    Number of weeks from the date of first dose of study treatment to the first date of objectively determined progressive disease (PD) (per modified RECIST for MPM) or death from any cause, estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CI). Subjects who do not experience PD and are alive on or before the data cut-off date will be censored at the time of last tumor assessment or data cut-off date, whichever is earlier.
  • Improvement in Pulmonary Function [ Time Frame: Subjects tested by spirometry at Screening and up to 7 days prior to dosing every other cycle starting at Cycle 3 until 4 weeks post final dose, assessed up to 16 weeks. ]
    Percentage of subjects with improvement in forced vital capacity (FVC), defined as an increase from baseline of either ≥400 mL or ≥20% assessed using spirometry
  • Overall Survival (OS) [ Time Frame: OS was assessed from the first dose of study treatment until death or study termination, whichever is earlier, assessed up to 25 weeks. ]
    Number of weeks from the date of first dose of study treatment to the date of death from any cause, estimated using KM methods with 95% CIs for subjects in the SAF. Subjects without documentation of death at the time of analysis were censored as of the date the subject was last known to be alive, or the data cut-off date, whichever is earlier.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 2, 2017)
  • Disease Control Rate [ Time Frame: Through study completion, an average of 18 months ]
    Defined as the percentage of subjects with CR, PR, or stable disease (SD)
  • Progression Free Survival [ Time Frame: Through study completion, an average of 18 months ]
    Defined as time from first dose of study drug until disease progression or death
  • Improvement in pulmonary function (FVC) [ Time Frame: Through study completion, an average of 18 months ]
    Proportion of subjects with improvement in pulmonary function (FVC), defined as an increase from baseline of either ≥400 mL or ≥20% assessed using spirometry
  • Overall Survival (OS) [ Time Frame: Through study completion, an average of 18 months ]
    As measured from date of first dose of study drug until death
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of CRS-207 With Pembrolizumab in Previously Treated Malignant Pleural Mesothelioma (MPM)
Official Title  ICMJE A Phase 2 Single-arm Study to Evaluate Safety and Efficacy of CRS-207 With Pembrolizumab in Adults With Previously-Treated Malignant Pleural Mesothelioma
Brief Summary The purpose of this study is to evaluate whether CRS-207 with pembrolizumab is safe and effective in adults with MPM who have failed prior anti-cancer therapy.
Detailed Description The population for this study will consist of approximately 35 adults with histologically-confirmed MPM (epithelial or biphasic) whose disease has progressed after 1-2 prior anti-cancer therapies.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Malignant Pleural Mesothelioma
Intervention  ICMJE
  • Biological: CRS-207
    Administered by IV infusion over approximately 1 hour.
  • Biological: Pembrolizumab
    Administered by IV infusion over approximately 30 minutes.
    Other Name: MK-3475
Study Arms  ICMJE Experimental: Experimental
CRS-207 and pembrolizumab will be administered in 3-week cycles. For Cycle 1, pembrolizumab (200 mg) will be administered by intravenous (IV) infusion over 30 minutes on Day 1 and CRS-207 (starting dose 1 × 10e9 colony-forming units [CFU]) will be administered by IV infusion over 1 hour on Day 2. If the infusions are well tolerated, pembrolizumab and CRS-207 may be administered on the same day (Day 1) for subsequent cycles. After 4 cycles, pembrolizumab will continue to be administered on Day 1 at each treatment cycle (every 3 weeks); CRS-207 will be administered once every 6 weeks (every other cycle). Treatment will continue for up to 35 cycles as long as there is adequate safety and potential for clinical benefit.
Interventions:
  • Biological: CRS-207
  • Biological: Pembrolizumab
Publications * Byrne MJ, Nowak AK. Modified RECIST criteria for assessment of response in malignant pleural mesothelioma. Ann Oncol. 2004 Feb;15(2):257-60.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 26, 2019)
10
Original Estimated Enrollment  ICMJE
 (submitted: June 2, 2017)
35
Actual Study Completion Date  ICMJE January 31, 2018
Actual Primary Completion Date January 9, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Histologically-confirmed epithelial or biphasic MPM; biphasic tumors must have a predominantly (≥50%) epithelial component
  2. No more than 2 prior lines of anti-cancer therapy, one of which must have included pemetrexed and a platinum.
  3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  4. Adequate organ and marrow function
  5. Adequate lung function; forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) ≥ 45% of predicted value as measured by spirometry; and oxygen saturation ≥ 90% on room air

Exclusion Criteria

  1. Pleurodesis within 14 days prior to first dose of study drug
  2. Receiving tumor necrosis factor (TNF) pathway inhibitors, PI3 kinase inhibitors, systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
  3. Active secondary malignancy
  4. Prior anti-cancer monoclonal antibody within 4 weeks prior to first dose of study drug, or not recovered from adverse effects due to agents administered more than 4 weeks earlier
  5. Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to first dose of study drug
  6. History of (non-infectious) pneumonitis that required steroids or current pneumonitis
  7. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent, or agents targeting other checkpoint pathways (e.g. CTLA-4)
  8. Prior immunotherapy with CRS-207 or any other Listeria-based agent, therapeutic cancer vaccine, or adoptive T cell immunotherapy
  9. Implanted medical devices that pose high risks for colonization and cannot be easily removed (e.g., artificial heart valves, pacemakers, prosthetic joints, orthopedic screw(s), metal plate(s)) if infection occurs. Other common devices such as venous access devices (e.g., Port-a-Cath or Mediport) may be permitted as well as arterial and venous stents and dental and breast implants that were placed more than 3 months prior to first dose of study drug.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03175172
Other Study ID Numbers  ICMJE ADU-CL-13
KEYNOTE KN-701 ( Other Identifier: (Other Identifier: Merck Sharp & Dohme Corp) )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Aduro Biotech, Inc.
Study Sponsor  ICMJE Aduro Biotech, Inc.
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE Not Provided
PRS Account Aduro Biotech, Inc.
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP