Infliximab vs Vedolizumab for Colitis from Immunotherapy in Cancer Patients

Overseen By Yinghong Wang

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Immune checkpoint inhibitors

Must not be taking: Immunosuppressive therapies

Disqualifiers: Under 18, Pregnancy, Inflammatory bowel, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 6 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, infliximab and vedolizumab, both monoclonal antibodies, to evaluate their effectiveness in treating colitis, a type of colon inflammation caused by cancer immunotherapy. The research aims to identify the best treatment for this side effect in patients with genitourinary cancers, melanoma, or lung cancer. Suitable participants have experienced serious diarrhea or colitis after using immune checkpoint inhibitors for cancer treatment. Participants will receive either infliximab or vedolizumab through an IV over several weeks to determine which treatment works better with fewer side effects. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatments work in people and measuring their effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on other immunosuppressive therapies while participating. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that both infliximab and vedolizumab have promising safety records from past studies.

For infliximab, research on patients with ulcerative colitis indicates it is generally well-tolerated. Patients did not experience more severe side effects than with other treatments like steroids or immune-suppressing drugs. Infliximab's FDA approval for other conditions suggests it is considered safe.

Vedolizumab also has a good safety record. Studies with ulcerative colitis patients show that vedolizumab is effective and safe over the long term. However, some serious infections have been reported in rare cases.

Both treatments have been used in patients with conditions similar to those in this trial, which increases confidence in their safety for treating colitis caused by cancer immunotherapy. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for colitis caused by immunotherapy in cancer patients focus on suppressing the inflammation with corticosteroids. However, Infliximab and Vedolizumab offer different approaches. Infliximab is a monoclonal antibody that targets and blocks tumor necrosis factor-alpha (TNF-alpha), a protein that plays a significant role in inflammation. On the other hand, Vedolizumab is unique because it specifically targets the gut by blocking a protein called integrin, which helps immune cells move into the gut tissue, thereby reducing inflammation selectively in the gut. Researchers are excited about these treatments because they offer targeted options that might lead to fewer side effects compared to traditional systemic immunosuppressants.

What evidence suggests that this trial's treatments could be effective for colitis caused by immunotherapy?

This trial will compare the effectiveness of infliximab and vedolizumab in treating colitis caused by cancer immunotherapy. Research has shown that infliximab, administered to participants in Arm I, has a response rate of about 87%, indicating that most patients experienced an improvement in their colitis symptoms. Vedolizumab, given to participants in Arm II, shows similar results, with about 89% of patients seeing their symptoms disappear. Although both treatments work well, infliximab might have a higher chance of colitis returning. Vedolizumab, however, may help reduce the need for steroids, which often control inflammation. Both treatments appear to be promising options for managing this type of colitis. ^{1 6 7 8 9}

Who Is on the Research Team?

Yinghong Wang

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with genitourinary cancer, melanoma, or non-small cell lung cancer who have developed grade 2 or higher colitis from immune checkpoint inhibitor therapy. They must not have active GI infections, inflammatory bowel disease, radiation enterocolitis, or be on other immunosuppressive drugs. Pregnant women and those under 18 are excluded.

Inclusion Criteria

I don't have an active GI infection as confirmed by tests or my doctor.

I have genitourinary cancer, melanoma, or non-small cell lung cancer.

I can understand and am willing to sign the informed consent.

Exclusion Criteria

I do not have active inflammatory bowel disease or radiation enterocolitis.

I developed side effects not related to my digestive system when I started the study treatment.

I still have a GI infection after 5 days of antibiotics.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive infliximab or vedolizumab intravenously over 1 hour at weeks 0, 2, and 6 for a total of 3 doses

6 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Weekly visits for 1 month, then at 2 and 3 months

Long-term follow-up

Participants are monitored for long-term outcomes and survival

Up to 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Infliximab
• Vedolizumab

Trial Overview The study is testing the effectiveness of monoclonal antibodies infliximab and vedolizumab in treating colitis caused by immune checkpoint inhibitors in patients with certain cancers. It aims to determine the best treatment strategy for this condition.

How Is the Trial Designed?

Group I: Arm II (vedolizumab) Experimental Treatment 1 Intervention

Patients receive vedolizumab IV over 1 hour at week 0, 2, 6 for a total of 3 doses in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (infliximab) Active Control 1 Intervention

Patients receive infliximab IV over 1 hour once at week 0, 2, 6 for a total of 3 doses in the absence of disease progression or unacceptable toxicity.

Infliximab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Remicade for:

• Ankylosing Spondylitis
• Crohn's Disease
• Ulcerative Colitis
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Plaque Psoriasis

Approved in United States as Remicade for:

• Ankylosing Spondylitis
• Crohn's Disease
• Ulcerative Colitis
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Plaque Psoriasis

Approved in Canada as Remicade for:

• Ankylosing Spondylitis
• Crohn's Disease
• Ulcerative Colitis
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Plaque Psoriasis

Approved in Japan as Remicade for:

• Ankylosing Spondylitis
• Crohn's Disease
• Ulcerative Colitis
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Plaque Psoriasis

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study comparing adverse events (AEs) in patients with inflammatory bowel diseases treated with adalimumab (ADA) and vedolizumab (VDZ), VDZ showed a significantly lower incidence of AEs leading to drug withdrawal (5.3 per 100 person-years) compared to ADA (13.2 per 100 person-years), indicating a 76% lower risk for VDZ.

While both treatments had similar overall rates of AEs not causing drug interruption, the findings suggest that VDZ may be a safer option for long-term treatment in IBD patients, warranting further real-life studies to confirm these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence comparison of adverse events in patients with inflammatory bowel disease receiving different biologic agents: retrospective long-term evaluation. Barberio, B., Savarino, EV., Card, T., et al.[2022]

In a study of 795 biologic-naïve ulcerative colitis patients, infliximab and vedolizumab showed similar effectiveness in achieving clinical remission and response at week 6.

However, infliximab was associated with significantly higher rates of corticosteroid-free clinical remission and endoscopic remission after one year compared to vedolizumab, suggesting it may offer additional long-term benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Efficacy for Infliximab Vs Vedolizumab in Biologic Naive Ulcerative Colitis. Narula, N., Wong, ECL., Marshall, JK., et al.[2022]

Infliximab has shown significant efficacy in treating inflammatory bowel disease, particularly Crohn's disease and ulcerative colitis, leading to increased rates of steroid-free remission and improved quality of life for patients.

Real-world data supports the findings from randomized controlled trials, indicating that infliximab not only helps manage symptoms but may also reduce hospitalization and the need for surgery in patients with these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of infliximab for luminal and fistulizing Crohn's disease and in ulcerative colitis. Behm, BW., Bickston, SJ.[2022]

Infliximab is an effective treatment for severe inflammatory bowel disease (IBD) and was generally well tolerated in a study of 100 patients, with no fatal complications or serious long-term side effects observed.

While most patients experienced few adverse events, including some infections and infusion reactions, the overall safety profile was positive, suggesting that infliximab can be a safe option when patients are carefully monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety aspects of infliximab in inflammatory bowel disease patients. A retrospective cohort study in 100 patients of a German University Hospital. Seiderer, J., Göke, B., Ochsenkühn, T.[2019]

Infliximab is an effective treatment for inducing and maintaining remission in adults with active Crohn's disease, supported by large randomized controlled trials, while its efficacy in children and adolescents is backed by smaller studies.

Safety concerns include severe infections and infusion reactions, with a recommended treatment strategy involving three initial infusions followed by maintenance doses every eight weeks, suggesting that early intervention may improve outcomes in Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infliximab use in children and adolescents with inflammatory bowel disease. de Ridder, L., Benninga, MA., Taminiau, JA., et al.[2015]

In a systematic review and meta-analysis of over 1900 participants, infliximab showed superior efficacy compared to vedolizumab during the induction phase for both Crohn's disease and ulcerative colitis, achieving better clinical response and remission rates.

During the maintenance phase, both infliximab and vedolizumab had similar efficacy and safety profiles, with comparable rates of adverse events, although the infection rates varied between the two treatments depending on the disease type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of infliximab and vedolizumab therapy in patients with inflammatory bowel disease: a systematic review and meta-analysis. Peyrin-Biroulet, L., Arkkila, P., Armuzzi, A., et al.[2022]

In a study of 257 patients with inflammatory bowel disease receiving either infliximab or vedolizumab, higher levels of infliximab were statistically associated with the occurrence of adverse events (AEs), particularly when excluding common symptoms like fatigue and abdominal pain.

Vedolizumab levels above 18 μg/mL were also linked to an increase in AEs, but no specific adverse events were directly associated with higher drug levels, indicating that while AEs are rare, further research is needed to clarify these relationships.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Infliximab and Vedolizumab Trough Levels with Reported Rates of Adverse Events: A Cross-Sectional Study. Veisman, I., Barzilay, O., Bruckmayer, L., et al.[2021]

Vedolizumab is an effective treatment for adults with moderately to severely active ulcerative colitis and Crohn's disease who do not respond to or cannot tolerate conventional therapies or anti-TNFα agents, as shown in pivotal clinical trials.

The review highlights vedolizumab's safety and tolerability based on both randomized controlled trials and real-world experiences, suggesting it has a favorable profile for patients with inflammatory bowel disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vedolizumab for inflammatory bowel disease: From randomized controlled trials to real-life evidence. Scribano, ML.[2018]

Vedolizumab is a monoclonal antibody that effectively targets the α4β7 integrin to inhibit gut lymphocyte trafficking, providing a safe treatment option for patients with moderate to severe Crohn's disease and ulcerative colitis.

Unlike anti-TNF agents, which some patients may become intolerant to or lose response over time, vedolizumab offers a promising alternative for those who are primary nonresponders or have developed antidrug antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vedolizumab as a Treatment for Crohn's Disease and Ulcerative Colitis. Ha, C., Kornbluth, A.[2022]

In a study of 232 adult patients receiving maintenance therapy for Inflammatory Bowel Disease, 58% of those on infliximab and 59% on vedolizumab opted to switch from intravenous to subcutaneous injections, indicating a strong uptake of this treatment method.

The primary motivation for patients to switch to subcutaneous injections was time savings, with 68% of switchers citing this reason, while other factors like COVID-19 exposure risk or financial savings did not significantly influence the decision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uptake of a Switching Program for Patients Receiving Intravenous Infliximab and Vedolizumab to Subcutaneous Preparations. Burdge, G., Hardman, A., Carbery, I., et al.[2022]

In a study of 48 patients with inflammatory bowel disease resistant to anti-tumor necrosis factor therapy, vedolizumab was effective, with 63% of patients responding to treatment and 42% achieving remission over a mean duration of 4.5 months.

Vedolizumab demonstrated a favorable safety profile, with no significant side effects reported during the 3-month follow-up, making it a viable treatment option for patients unable to tolerate traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Vedolizumab in Inflammatory Bowel Disease: A Single-Center Experience. Erdoğan, Ç., Yeşil, B., Bacaksız, F., et al.[2022]

This study provides real-world evidence from 9 Irish hospitals supporting the safety and efficacy of vedolizumab in treating inflammatory bowel disease (IBD), particularly in patients who have previously been treated with anti-TNF agents.

The results align with larger international studies and offer insights into potential predictors of treatment response, helping to clarify vedolizumab's role in the treatment algorithm for IBD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irish data on the safety and efficacy of vedolizumab in the treatment of inflammatory bowel disease. Judge, C., McGettigan, N., Ryan, T., et al.[2021]

In a study of 184 patients with immune-mediated diarrhea and colitis (IMDC), both vedolizumab and infliximab showed similar efficacy in achieving clinical remission (89% vs 88%), but vedolizumab resulted in shorter steroid exposure and fewer hospitalizations.

Vedolizumab treatment was associated with a longer time to clinical response compared to infliximab, but overall, it led to lower IMDC recurrence rates and better patient outcomes, highlighting its potential advantages in managing IMDC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of vedolizumab and infliximab treatment for immune-mediated diarrhea and colitis in patients with cancer: a two-center observational study. Zou, F., Faleck, D., Thomas, A., et al.[2022]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK605543/

Infliximab for Immune Checkpoint Inhibitor Therapy ... - NCBI Treatment with infliximab as compared with vedolizumab resulted in comparable immune-induced colitis response rates, higher recurrent rate of colitis, and more ...

2. esmoopen.com esmoopen.com/article/S2059-7029(24)01401-7/fulltext

A 1-year follow-up study on checkpoint inhibitor-induced ... The 12-month clinical remission rate was 47.7 per 100 person-years [95% confidence interval (CI) 33.5-67.8). ICI was discontinued due to colitis ...

3. journals.lww.com journals.lww.com/ajg/fulltext/2023/10001/s314_efficacy_of_infliximab_and_vedolizumab_in.434.aspx

S314 Efficacy of Infliximab and Vedolizumab in Immune... In further subgroup analysis, treatment with infliximab led to a response rate of 86.65% (95% CI 81.37 - 91.92) and treatment with vedolizumab led to a response ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0305737222001098

Immune checkpoint Inhibitor–Induced diarrhea and Colitis Measured by clinical remission of symptoms, infliximab (5 mg/kg) was efficient in 87% of patients (95% CI 79% to 94%; 502 patients) and vedolizumab in a flat- ...

5. jitc.bmj.com jitc.bmj.com/content/9/11/e003277

Efficacy and safety of vedolizumab and infliximab treatment ... Conclusions Treatment with vedolizumab as compared with infliximab for IMDC led to comparable IMDC response rates, shorter duration of steroid ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00096655

NCT00096655 | A Safety and Efficacy Study for Infliximab ... This study is designed to investigate the safety and effectiveness of infliximab in adult patients with active ulcerative colitis. The purpose of this study is ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39660680

Long-Term Outcomes of an Infliximab-First Versus ... - PubMed In patients with UC, long-term effectiveness and safety outcomes are comparable with infliximab-first and vedolizumab-first treatment strategies at 30 months.

8. bmcgastroenterol.biomedcentral.com bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-025-04065-w

Infliximab for patients with moderate to severely active ... IFX has a more positive effect on active UC than placebos, aminosalicylic acid preparations, steroids, or immunosuppressive drugs, but shows no superiority in ...

9. yoda.yale.edu yoda.yale.edu/clinical-trial/nct01551290-a-phase-3-multicenter-randomized-double-blind-placebo-controlled-study-evaluating-the-efficacy-and-safety-of-infliximab-in-chinese-subjects-with-active-ulcerative-colitis/

NCT01551290 - The YODA Project A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Infliximab in Chinese Subjects With Active ...