Food Intervention to Reduce Immunotherapy toXicity (FORX01)

The FORX (Food intervention to Reduce immunotherapy toXicity) trial will assess whether supplementing dietary fiber intake by providing weekly boxes containing 30 different plants to patients with solid tumors starting immune checkpoint inhibitor therapy affects the incidence of immune related adverse events.

Study Overview

• Status: Recruiting
• Conditions: Dietary Habits; Immune-related Adverse Event
• Intervention / Treatment: Other: Food box containing 30 different plants

Detailed Description

Immune checkpoint inhibitor (ICI) therapy has revolutionized cancer treatment but can give rise to immune related adverse events (irAEs) that are currently not preventable. These irAEs impact patients' quality of life and oncological treatment course. The gut plays an essential role in immune homeostasis and gut dysbiosis is implicated in (auto)inflammatory conditions. The FORX trial investigates whether the composition of the gut microbiome can be altered to improve ICI tolerance. It has been shown that healthy volunteers who ingest at least 30 different plants (vegetables, fruits, nuts) weekly, have a more diverse microbiome than those who consume 10 or less. A fiber-rich diet has been associated with improved outcome of ICI treatment. This trial is the first prospective trial to translate these findings into a concrete dietary advice. The diets of patients with a solid tumor who start ICI will be supplemented by weekly boxes containing 30 different plants during the first 12 weeks of their treatment. The increased fiber intake is expected to strengthen the gut microbiome and reduce the incidence of irAEs. Stool and blood samples will clarify the microbial and cytokine signatures associated with irAEs. The FORX trial will provide valuable insights in the interaction between the gut microbiome and autoimmunity and serve as a basis for nutritional advice and the development of targeted probiotics. It will empower cancer patients and improve their quality of life.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marthe Verhaert, MD; Phone Number: +3224749480; Email: marthe.verhaert@uzbrussel.be
• Study Contact Backup: Name: Sandrine Aspeslagh, MD PhD; Email: sandrine.aspeslagh@uzbrussel.be

Study Locations

• Belgium
  • Jette, Belgium, 1090
    • Recruiting
    • UZ Brussel
    • Contact: Sandrine Aspeslagh, MD, PhD; Email: sandrine.aspeslagh@uzbrussel.be
    • Contact: Marthe Verhaert, MD; Phone Number: +3224779480; Email: marthe.verhaert@uzbrussel.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• solid tumor starting anti-programmed cell death protein 1 (anti-PD1) and/or anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA4) antibodies as part of standard of care.
• able to sign informed consent.

Exclusion Criteria:

• no oral intake possible.
• probiotic use and unwillingness to stop during the trial.
• combination therapy with chemotherapy or targeted agents.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: High Fiber diet; During the first 12 weeks of immune checkpoint inhibitor therapy, patients will receive weekly boxes containing 30 different plants (vegetables, fruits, nuts, grains) according to seasonal availability following the Flemish Superior Health Council guidelines. Recipes will be added to inspire processing of the box. Boxes will be ordered at an online supermarket, who will deliver the boxes at patients' homes. Weekly follow-up will ensure a minimum daily intake of 20 g of fiber, progressively increasing over the first 4 weeks.

Other: Food box containing 30 different plants; Food boxes during first 12 weeks of therapy. Clinical follow-up until end of immunotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of performing a dietary intervention trial in our center	Recruitment will be temporarily held after 10 patients to assess compliance with protocol and dietary intervention. If at least 7/10 patients are able to complete the 12 weeks according to protocol, the trial will be considered feasible and recruitment will continue.	12 weeks
Incidence of immune related adverse events	Assess incidence and grade of irAEs throughout the 12-week intervention phase and until end of ICI treatment by frequency counts and grade. Comparison with historical control.	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	Measure objective response rate at 12 weeks and progression free survival at week 12, 24 and 48 according to RECIST 1.1. Observational comparison with historical control.	up to 48 weeks
Quality of life	Assess change in quality of life following dietary intervention using European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and Hospital Anxiety and Depression Score (HADS) questionnaire at baseline, at 6 weeks and at 12 weeks.	12 weeks
Changes in gut microbiota	Assess changes in gut microbiota composition following dietary intervention. Assess microbiota signatures associated with irAEs.	12 weeks and in case of an irAE up to 48 months
Assess changes in cytokines and immune cell subsets associated with irAEs	Blood samples will be collected at baseline, every 4 weeks for 12 weeks during the intervention and in case of toxicity. Based on published data, the investigators will primarily focus on Th17-related cytokines (IL-6, IL-17, IL-23, IFN-gamma). PBMC will be analysed using high dimensional flow cytometry, using panels to measure different immune cell subsets (T cells and subtypes, B cells, among which regulatory B cells). Analysis using regression models.	12 weeks and in case of an irAE up to 48 months

Collaborators and Investigators

• Sponsor: Universitair Ziekenhuis Brussel
• Investigators: Principal Investigator: Sandrine Aspeslagh, MD PhD, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel)

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: March 21, 2023
• First Submitted That Met QC Criteria: April 14, 2023
• First Posted (Actual): April 27, 2023

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: FORX01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No