Ustekinumab for Diarrhea and Colitis in Cancer Patients

Overseen By Yinghong Wang, MD,PHD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressive therapies, Biologics

Disqualifiers: Under 18, Pregnancy, Infections, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if ustekinumab can manage diarrhea and colitis (inflammation of the colon) related to immune therapy in cancer patients. Ustekinumab may help control these side effects. Individuals experiencing moderate immune-related diarrhea or colitis due to cancer treatment might be suitable for this study. Participants should not have active gastrointestinal infections. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that patients on certain immunosuppressive therapies cannot participate, so it's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that ustekinumab is likely to be safe for humans?

Research has shown that ustekinumab has been thoroughly studied for safety. In a large study, 2,575 patients with inflammatory bowel disease used ustekinumab, and researchers tracked their health over 4,826 patient-years. This extensive monitoring covered many years and patients.

The results indicated that the treatment was consistently safe, without causing unexpected problems. Common side effects were mild, such as headaches and tiredness, while serious side effects were rare.

The FDA has also approved ustekinumab for treating other conditions, like ulcerative colitis, suggesting it is generally well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ustekinumab is unique because it targets specific proteins in the immune system, which may help reduce inflammation more precisely than traditional treatments like corticosteroids or immunosuppressive drugs. This precision could mean fewer side effects and better management of diarrhea and colitis in cancer patients. Researchers are excited about ustekinumab because its targeted approach might offer a new way to control symptoms for patients who don't respond well to current therapies.

What evidence suggests that ustekinumab might be an effective treatment for diarrhea and colitis in cancer patients?

Research has shown that ustekinumab can help treat inflammatory bowel conditions, similar to the immune-related colitis and diarrhea experienced by some cancer patients. In one study, 42% of patients experienced significant symptom improvement, reaching clinical remission, while 52% responded positively to the treatment. Another study found that ustekinumab helped patients with ulcerative colitis, with about half showing improvement and some achieving full remission. These findings suggest that ustekinumab, which participants in this trial will receive, may help manage symptoms in conditions involving gut inflammation, such as immune-related colitis and diarrhea in cancer patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Yinghong Wang, MD,PHD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adult cancer patients with immune-related diarrhea or colitis from checkpoint inhibitor therapy. They must not have GI infections, inflammatory bowel disease, or be on other immunosuppressives. Pregnant women and those under 18 are excluded.

Inclusion Criteria

No concern for active concomitant GI infection for immune-related diarrhea and/or colitis work up at the time of protocol therapy initiation as confirmed by stool tests or as per the treating physician based on clinical presentation

I am receiving immunotherapy.

Patient who has been cleared for enrollment by Infectious Diseases consultant or treating physician if positive infection workup or screening tests (e.g. lifelong positive T-spot due to BCG inoculation, chronic colonization) prior to initiation of diarrhea/colitis treatment

Exclusion Criteria

I am under 18 years old.

Pregnant and breastfeeding women

I am experiencing side effects not related to my digestive system from my current treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ustekinumab to control immune-related diarrhea and/or colitis

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Ustekinumab

Trial Overview The study tests if ustekinumab can control immune-related diarrhea/colitis in cancer patients who've had grade 2 or higher symptoms within the last 45 days after receiving any type of ICI therapy.

How Is the Trial Designed?

Group I: Single Arm Experimental Treatment 1 Intervention

Participants will be identified per the evaluation of primary oncology and/or gastroenterology consult services.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Janssen Research & Development, LLC

Industry Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

A study involving 117 Crohn's disease patients, including 39 elderly (≥65 years) and 78 nonelderly (<65 years), found that ustekinumab (UST) is safe and effective for treating elderly patients, with nearly 90% experiencing a clinical response.

Elderly patients were less likely to achieve complete clinical remission compared to nonelderly patients (28.2% vs. 52.6%), but there were no significant differences in adverse events or complications between the two age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Effectiveness and Safety of Ustekinumab in Elderly Crohn's Disease Patients. Garg, R., Aggarwal, M., Butler, R., et al.[2023]

In a study of 34 Crohn's disease patients who previously failed anti-TNF therapies, ustekinumab (UST) achieved a clinical remission rate of 70.5%, indicating its efficacy as a treatment option for these patients.

UST was particularly effective in patients with fistulizing disease, with a 70% remission rate, suggesting it may be a preferred treatment for this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

P066 Real-World Experience of Ustekinumab in Crohn's Disease Patients With Prior Anti-TNF Therapy at a Tertiary Care Hospital. Tripathi, K., Groudan, K., Chalhoub, J., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10636694/

Clinical Outcomes of Ustekinumab in Inflammatory Bowel ... On the last follow-up beyond week 16, 42% achieved clinical remission and 52% responded to the treatment. The study concluded with the idea that ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06807593

Treatment of Immune Checkpoint Inhibitor-related Diarrhea ... The goal of this clinical research study is to learn if ustekinumab can help to control immune-related diarrhea and/or colitis in cancer patients. Detailed ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2405803325001748

Clinical perspective and treatment of immune-related colitis ... Treatment of ICI-related diarrhea and/or colitis with ustekinumab in cancer patients ... effective in ICI-colitis, but showed variable results ...

4. academic.oup.com academic.oup.com/ecco-jcc/article/19/6/jjaf091/8155306

Cancer incidence in patients with ulcerative colitis naïve to or ... The IR differences were not significantly increased in patients treated with ustekinumab 0.57 (HR: 0.87;0,39-1.93) and tofacitinib −0.69 (HR: ...

5. scholars.mssm.edu scholars.mssm.edu/en/publications/real-world-effectiveness-of-ustekinumab-in-ulcerative-colitis-in-

Real-World Effectiveness of Ustekinumab in Ulcerative Colitis ... Of the 73 that were dose escalated, 28.4% did not respond, 49.3% experienced a benefit, and 21.6% achieved remission. Conclusions: In a ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11302965/

Safety of Ustekinumab in Inflammatory Bowel Disease In this final pooled safety analysis, 2575 patients were treated with ustekinumab with 4826 patient-years of follow-up. Rates of key safety events, including ...

7. stelarahcp.com stelarahcp.com/ulcerative-colitis/safety

Ulcerative Colitis (UC): Safety Profile - Stelara View STELARA® (ustekinumab) safety profile data, including common adverse reactions and additional safety information. See full Prescribing & Safety Information

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06807593?cond=Cancer%20Therapy-Related%20Diarrhea&rank=8

Treatment of Immune Checkpoint Inhibitor-related Diarrhea ... A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the goal is to ...

9. jnjmedicalconnect.com jnjmedicalconnect.com/products/stelara/medical-content/stelara-occurrence-of-malignancies

STELARA - Occurrence of Malignancies A summary of safety data regarding the occurrence of malignancies in patients receiving STELARA® (ustekinumab).

10. jnj.com jnj.com/media-center/press-releases/new-stelara-ustekinumab-long-term-data-support-its-established-safety-profile-in-inflammatory-bowel-disease-and-durable-efficacy-in-ulcerative-colitis

New STELARA® (ustekinumab) Long-Term Data Support ... A final pooled safety analysis of six Phase 2/3 IBD studies included 2,575 patients treated with STELARA and a total of 4,826 patient-years (PY) ...