Prospective Analysis of Intestinal Microbiome and Autoimmune Panels as Predictors of Toxicity in ImmunOncology Patients

Titre officiel

Prospective Analysis of Intestinal Microbiome and Autoimmune Panels as Predictors of Toxicity in ImmunOncology Patients

Sommaire:

Il s’agit d’une étude non interventionnelle, menée à l’initiative de l’investigateur dans un seul centre, visant à évaluer le rôle du microbiome intestinal et des épreuves de dépistage des troubles auto-immuns à titre de facteurs prédictifs d’apparition d’effets indésirables d’ordre immunitaire (EIOI) de grade ≥ 2 selon les critères CTCAE (Common Toxicity Criteria for Adverse Events) [version 5.0] pouvant nécessiter ou non une immunosuppression générale, chez des patients atteints de tumeurs solides au stade avancé recevant des traitements d’association immuno-oncologiques (I-O) au centre anticancéreux Princess Margaret. Il s’agit d’une étude à risque minime comprenant l’analyse d’échantillons de patients et ne comportant aucune intervention thérapeutique. L’étude portera sur une cohorte prospective de 120 patients, tout au plus, dont le recrutement se terminera au plus tard dans 18 mois. Les patients recevront un traitement d’association I-O selon leurs protocoles donnés dans leur autre essai clinique respectif ou selon leurs normes de soins; des échantillons seront prélevés chez ces patients à différents points multiples dans le temps. Aucune visite supplémentaire à l’hôpital ne sera nécessaire pour cette étude, puisque les évaluations de l’innocuité (sécurité) ont déjà été effectuées chez tous les patients durant leur participation à leur essai clinique respectif ou dans le cadre de leurs soins standard.

Description de l'essai

Primary Outcome:

• 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.

Secondary Outcome:

• Correlation between baseline intestinal microbiome composition to the development of ≥ Grade 2 CTCAE v5.0 irAEs and/or requiring systemic immunosuppression for irAEs.
• Correlation between baseline autoimmune panels to 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.
• 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.
• 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.
• 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.
• 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

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.

Voir cet essai sur ClinicalTrials.gov