The Gut Microbiome and Immune Checkpoint Inhibitor Therapy in Solid Tumors

Renal Cell Carcinoma Clinical Trial

— PARADIGM  

Official title:

The Gut Microbiome and Immune Checkpoint Inhibitor Therapy in Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05037825
• Other study ID #: Pro00054854
• Status: Recruiting
• Start date: November 22, 2021
• Est. completion date: September 14, 2028

Study information

• Verified date: April 2022
• Source: VastBiome
• Contact: Hanane Arib, MS
• Phone: 650-479-5539
• Email: Hanane[@]vastbiome.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The microbiome has the potential to serve as a robust biomarker of clinical response to immunotherapy. Additionally, microbial manipulation, through diet, exercise, prebiotics, probiotics, or microbially-derived metabolites, may prove to be beneficial in promoting anti-tumor immune responses. However, large prospective studies in humans with longitudinal sample collection and standardized methods are needed to understand how microbiota and their byproducts affect cancer therapies, particularly among patients undergoing identical therapy but experiencing different outcomes. The proposed observational study builds upon these hypotheses by proposing a large cohort design to further assess the associations between the gut microbiota (composition and function), host immune system, and ICI treatment efficacy across multiple cancer types.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 800
• Est. completion date: September 14, 2028
• Est. primary completion date: September 14, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Men or women =18 years of age

2. Screened negative for COVID-19 symptoms at time of consent, as per institutional policy and as applicable for the duration of the COVID-19 pandemic

3. Diagnosed with stages I-IV primary NSCLC, MM, TNBC or RCC

4. Plan to be treated at a partner cancer site with a checkpoint inhibitor (anti-PD-1, anti-PD-L1, or anti-CTLA-4) as a single agent or in combination with another checkpoint inhibitor or other treatment agent or modality (e.g., targeted therapy, chemotherapy, surgery, radiation, etc.) in accordance with FDA-labeled use of the agent

5. Able to provide informed consent and answer study questionnaires in either English or Spanish

6. Able to provide stool specimens for research purposes

Exclusion Criteria:

1. Mental incapacity

2. Incarcerated individuals

3. Pregnancy (by self-report of pregnancy status)

4. Experiencing active brain metastasis/metastases

5. Treatment with checkpoint inhibitor in off-label capacity or through a clinical/interventional trial

6. Active participation in an immuno-oncology clinical/interventional trial or pharma-sponsored observational study

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Renal Cell
• Malignant Melanoma
• Melanoma
• Non-Small-Cell Lung Carcinoma
• Renal Cell Carcinoma
• Triple Negative Breast Neoplasms
• Triple-Negative Breast Cancer

Intervention

Drug:
• Checkpoint Inhibitor, Immune
anti-PD-1, anti-PD-L1, or anti-CTLA-4 as a single agent or in combination with another checkpoint inhibitor or other treatment agent or modality (e.g., targeted therapy, chemotherapy, surgery, radiation, etc.) in accordance with FDA-labeled use of the agent

Locations

Country	Name	City	State
United States	Baptist Health Clinical Research	Elizabethtown	Kentucky

Sponsors (1)

Lead Sponsor	Collaborator
VastBiome

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in microbiome composition from baseline to after Cycle 2 of checkpoint therapy (6-8 weeks) by analyzing longitudinally-collected stool specimens of 800 patients with primary NSCLC, MM, RCC, and TNBC	Microbiome evaluation with whole metagenome shotgun sequencing to assess changes in the relative abundance of microbial taxa (measured as percentage abundance per microbial species and changes in percentage abundance between baseline and cycle 2 timepoints) in patients who are receiving checkpoint blockade immunotherapy as the standard of care	prior to initiation of checkpoint therapy (i.e. "Baseline") and at the end of Cycle 2 of checkpoint blockade immunotherapy (at approximately 6-8 weeks) ]
Secondary	Microbiome samples correlation	Definition of a correlation between the gut microbiome and circulating cytokines (specifically IL-2, IL-10, TNF-alpha, IFN-gamma, and G-CSF) and therapeutic response (defined using RECIST criteria).	Time Frame: prior to initiation of checkpoint therapy (i.e. "Baseline") and at the end of Cycle 2 (at approximately 6-8 weeks)
Secondary	Microbiome correlation to blood biomarkers	Definition of a correlation between the gut microbiome (measured as percent abundance of microbial taxa derived from whole-metagenome shotgun sequencing) and plasma metabolites (measured in m/z and peak intensities and--where possible--compound abundances in ng/mL) and circulating cytokines (measured in pg/mL per cytokine) in patients receiving checkpoint blockade immunotherapy.	Time Frame: prior to initiation of checkpoint therapy (i.e. "Baseline") and at the end of Cycle 2 (at approximately 6-8 weeks)
Secondary	Blood samples correlation	Definition of a correlation between plasma metabolites (measured in m/z and peak intensities and--where possible--compound abundances in ng/mL) and circulating cytokines (measured in pg/mL per cytokine) and therapeutic response (defined using RECIST criteria).	Time Frame: prior to initiation of checkpoint therapy (i.e. "Baseline") and at the end of Cycle 2 (at approximately 6-8 weeks)