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Prospective Analysis of Intestinal Microbiome and Autoimmune Panels as Predictors of Toxicity in ImmunOncology Patients (INSPECT-IO)

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ClinicalTrials.gov Identifier: NCT04107311
Recruitment Status : Recruiting
First Posted : September 27, 2019
Last Update Posted : May 5, 2020
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto

Tracking Information
First Submitted Date September 23, 2019
First Posted Date September 27, 2019
Last Update Posted Date May 5, 2020
Actual Study Start Date September 5, 2019
Estimated Primary Completion Date March 5, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: September 26, 2019)
Feasibility of evaluating intestinal microbiome composition and autoimmune panels in patients treated with immunooncology combinations through the analysis of stool and blood samples at multiple time-points. [ Time Frame: 18 months ]
To assess the feasibility, the endpoint will be deemed feasible if >50% of patients have biospecimens collected in at least 2 time-points.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: September 26, 2019)
  • Correlation between baseline intestinal microbiome composition to the development of ≥ Grade 2 CTCAE v5.0 irAEs and/or requiring systemic immunosuppression for irAEs. [ Time Frame: 18 months ]
    Correlation between bacteria taxa obtained through 16S rRNA sequencing and irAEs.
  • Correlation between baseline autoimmune panels to the development of ≥ Grade 2 CTCAE v5.0 irAEs and/or requiring systemic immunosuppression for irAEs. [ Time Frame: 18 month ]
    Correlation between auto-antibodies detected through the 162 IgM and IgG antigen microarray with the development of ≥ Grade 2 CTCAE v5.0 irAEs and/or requiring systemic immunosuppression for irAEs.
  • Correlation between baseline fecal calprotectin levels to the development of ≥ Grade 2 CTCAE v5.0 colitis and/or requiring systemic immunosuppression for colitis. [ Time Frame: 18 months ]
    Correlation between fCal detection at baseline to development of ≥ Grade 2 CTCAE v5.0 irAEs and/or requiring systemic immunosuppression for irAEs.
  • Correlation between the early changes in composition of intestinal microbiome and the development of ≥ Grade 2 CTCAE v5.0 irAEs and/or requiring systemic immunosuppression for irAEs. [ Time Frame: 18 months ]
    Correlate changes in bacteria taxa composition through 16S rRNA sequencing from baseline samples to early time-point, with the development of ≥ Grade 2 CTCAE v5.0 irAEs and/or requiring systemic immunosuppression for irAEs
  • Correlation between the early changes in composition of autoimmune panels and the development of ≥ Grade 2 CTCAE v5.0 irAEs and/or requiring systemic immunosuppression for irAEs. [ Time Frame: 18 months ]
    Correlate the changes of auto-immune antibodies reactivity obtained through the 162 IgM and IgG antigen microarray from baseline to early time-point with the development of ≥ Grade 2 CTCAE v5.0 irAEs and/or requiring systemic immunosuppression for irAEs.
  • Correlation between the early changes in fecal calprotectin levels to the development of ≥ Grade 2 CTCAE v5.0 colitis and/or requiring systemic immunosuppression for colitis. [ Time Frame: 18 months ]
    Correlate the changes in fCal positivity from baseline to early time-point with the development of ≥ Grade 2 CTCAE v5.0 colitis and/or requiring systemic immunosuppression for colitis.
  • Evaluate intestinal microbiome, autoimmune panel reactivity & fCal changes from baseline to development of ≥ Gr2 CTCAE v5.0 irAEs and/or requiring systemic immunosuppression for irAEs, & from event diagnosis to resolution to ≤ Gr1 CTCAE v5.0 irAEs [ Time Frame: 18 months ]
    Monitor changes in bacteria taxa through 16S rRNA sequencing; reactivity of autoimmune antibodies through 162 IgM and IgG antigen microarray; and positivity of fCal at baseline, early time-point, at the time of event diagnosis, and at the time of event resolution
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures
 (submitted: September 26, 2019)
  • Evaluate the overall response rate (ORR) of the enrolled cohort measured by RECIST v1.1 and iRECIST. [ Time Frame: 18 months ]
    ORR by RECIST v1.1 and iRECIST.
  • Evaluate the median progression-free survival (PFS) of the enrolled cohort measured by RECIST v1.1 and iRECIST. [ Time Frame: 18 months ]
    PFS by RECIST v1.1 and iRECIST.
  • Correlation between the baseline composition of the intestinal microbiome with PFS. [ Time Frame: 18 months ]
    Microbiome composition through 16S rRNA sequencing with PFS by RECIST v1.1 and iRECIST.
  • Correlation between the baseline composition of the intestinal microbiome with ORR. [ Time Frame: 18 months ]
    Microbiome composition through 16S rRNA sequencing with ORR by RECIST v1.1 and iRECIST.
  • Correlation between the baseline autoimmune panels with ORR. [ Time Frame: 18 months ]
    Correlate the reactivity of baseline auto-antibodies detected through the 162 IgM and IgG antigen microarray with ORR per RECIST v1.1 and iRECIST.
  • Correlation between the baseline autoimmune panels with PFS. [ Time Frame: 18 months ]
    Correlate the reactivity of baseline auto-antibodies detected through the 162 IgM and IgG antigen microarray with PFS per RECIST v1.1 and iRECIST.
  • Correlation between the change in composition of the intestinal microbiome at multiple time-points with ORR. [ Time Frame: 18 months ]
    Change in microbiome composition as outlined above with ORR per RECIST v1.1 and iRECIST.
  • Correlation between the change in composition of the intestinal microbiome at multiple time-points with PFS. [ Time Frame: 18 months ]
    Change in microbiome composition as outlined above with PFS per RECIST v1.1 and iRECIST.
  • Correlation between the change in autoimmune panels at multiple time-points with ORR. [ Time Frame: 18 months ]
    Change in reactivity of auto-immune antibodies as outlined above with ORR per RECIST v1.1 and iRECIST.
  • Correlation between the change in autoimmune panels at multiple time-points with PFS. [ Time Frame: 18 months ]
    Change in reactivity of auto-immune antibodies as outlined above with PFS per RECIST v1.1 and iRECIST.
  • Correlation between the composition of the intestinal microbiome at different time-points with radiomic analysis using voxels lying inside the tumor volume of interest. [ Time Frame: 18 months ]
    Correlation of bacteria taxa composition through 16S rRNA sequencing with radiomic analysis.
  • Correlation between the reactivity of autoimmune panels at different time-points with radiomic analysis using voxels lying inside the tumor volume of interest. [ Time Frame: 18 months ]
    Correlation of auto-immune antibodies as outlined above with radiomic analysis
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title Prospective Analysis of Intestinal Microbiome and Autoimmune Panels as Predictors of Toxicity in ImmunOncology Patients
Official Title Prospective Analysis of Intestinal Microbiome and Autoimmune Panels as Predictors of Toxicity in ImmunOncology Patients
Brief Summary

This is a single-center, investigator-initiated, non-interventional study evaluating the role of the intestinal microbiome and autoimmune panels as a predictor for developing ≥ Grade 2 CTCAE v5.0 immune-related adverse event (irAE) and/or requiring systemic immunosuppression for irAEs in advanced solid tumor patients receiving immunooncology (IO) combinations at the Princess Margaret Cancer Centre. This is a minimal risk study involving the analysis of patient samples and does not involve therapeutic intervention.

The study will involve a prospective cohort of up to 120 patients and it is anticipated that patient accrual will be completed within 18 months.

Patients will receive IO combination as per their specific protocols from their other clinical trial or per their standard of care and samples will be collected at multiple time-points. No additional visits to the hospital will be needed for this study as safety assessments are already captured for all patients based on their participation in a clinical trial or per their standard of care.

Detailed Description

Accumulating evidence supports that differential composition of fecal microbiome influences response to immunotherapy and development of colitis. Microbiome with different profiles are also associated with multiple diseases, including gastrointestinal (GI) or non-GI auto-immune pathologies. Little is known about the relationship between the microbiome composition or fecal calprotectin (fCal) and the development of non-colitis immune-related adverse events (irAEs) during treatment with IO combinations.

Autoimmune conditions and irAEs from immune checkpoint inhibitors (ICI) drugs both involve loss of tolerance to endogenous antigens and produce similar clinical presentations. ICI can increase humoral response. However, to date there is no evidence that autoimmune panels are correlated with the development of irAEs during IO combination therapy.

These findings suggest that analyzing the microbiome and autoimmune panels of patients treated with IO combinations at multiple time-points may be feasible. In addition, baseline, early shift and changes in microbiome and autoimmune panels at time of a serious irAE may be correlated with the development of serious irAEs and may change with appropriate immunosuppressive regimens.

We hypothesize that analysing the microbiome and autoimmune panels of patients treated with immunooncology (IO) combinations at multiple time-points is feasible. Additionally, we hypothesize that baseline, early shift and changes in microbiome and autoimmune panels at time of a serious immune-related adverse event (irAE) is correlated with the development of serious irAEs and will change with appropriate immunosuppressive regimens.

Study Type Observational
Study Design Observational Model: Other
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Stool and blood samples at multiple time-points in patients undergoing treatment with immunooncology (IO) combination therapy.
Sampling Method Non-Probability Sample
Study Population Advanced solid tumor patients receiving immunooncology combinations
Condition Solid Tumor
Intervention Not Provided
Study Groups/Cohorts Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: September 26, 2019)
120
Original Estimated Enrollment Same as current
Estimated Study Completion Date March 5, 2021
Estimated Primary Completion Date March 5, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  1. Signed written and voluntary informed consent.
  2. Patient must be willing and able to provide collection for blood and stool specimen analysis at the pre-specified time-points.
  3. Age > 18 years, male or female.
  4. Patient must be diagnosed with any advanced solid tumor deemed incurable and to be treated at Princess Margaret Cancer Centre.
  5. Patients must be eligible to treatment with an IO combination.

Exclusion Criteria:

  1. Any conditions that in the opinion of the Investigator would interfere with patient safety, or evaluation of the collected specimen and interpretation of study result.
  2. History of autoimmune disease with a flare episode within one year before study screening.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Anna Spreafico, MD 416-946-4501 ext 3308 tip@uhn.ca
Contact: Aileen Trang 416-946-4501 ext 7754 aileen.trang@uhn.ca
Listed Location Countries Canada
Removed Location Countries  
 
Administrative Information
NCT Number NCT04107311
Other Study ID Numbers INSPECT-IO-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party University Health Network, Toronto
Study Sponsor University Health Network, Toronto
Collaborators Not Provided
Investigators
Principal Investigator: Anna Spreafico, MD Princess Margaret Cancer Centre
PRS Account University Health Network, Toronto
Verification Date May 2020