Mesalamine to prevent colitis from ipilimumab plus nivolumab

Prophylactic Oral Mesalamine for the Prevention of Immune-Related Colitis in Patients Treated With Ipilimumab/Nivolumab

This trial will try giving mesalamine to adults with advanced melanoma who are starting ipilimumab plus nivolumab to see if it lowers the chance and severity of immune-related diarrhea and colitis.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: AHS Cancer Control Alberta (Academic / other)
• Drugs / interventions: prednisone
• Locations: 1 site (Edmonton, Alberta)
• Trial ID: NCT05663775 on ClinicalTrials.gov

What this trial studies

Adults with unresectable stage III or IV melanoma who are starting combination ipilimumab and nivolumab will receive prophylactic mesalamine alongside their immunotherapy. Participants will be followed through treatment with scheduled clinic visits, symptom monitoring, and laboratory tests to record the incidence and grade of immune-related diarrhea and colitis. The primary endpoints focus on the frequency and severity of GI immune-related adverse events, with safety and treatment interruptions as secondary outcomes. This is a phase 2 interventional trial conducted at the Cross Cancer Institute in Edmonton.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed unresectable stage III or IV melanoma who are planning to start ipilimumab plus nivolumab, are able to consent, and meet basic safety and pregnancy-test criteria are ideal candidates.

Not a fit: Patients with preexisting inflammatory bowel disease, active uncontrolled gastrointestinal conditions, current use of mesalamine, or inability to take the drug may not receive benefit from this approach.

Why it matters

Potential benefit: If successful, prophylactic mesalamine could reduce immune-related diarrhea and colitis, enabling fewer treatment interruptions and better quality of life.

How similar studies have performed: Mesalamine is effective for non–immune checkpoint inhibitor ulcerative colitis, but using mesalamine prophylactically to prevent ICI-related colitis is relatively novel and has limited prior clinical evidence.

Eligibility criteria

Inclusion Criteria:

1. Patients must be 18 years of age or older.
2. Patients with histologically confirmed, unresectable stage III or IV malignant melanoma.
3. Patients must be capable of providing consent to enrolment and treatment.
4. Patients with a performance status of ECOG 0-224 will be eligible for enrolment (see appendix16.1).
5. Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test at the time of screening. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy or bilateral salpingectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes. In addition, females under the age of 55 years must have a serum follicle stimulating hormone, (FSH) level \> 40 mIU/mL to confirm menopause.
6. Patients of childbearing / reproductive potential should use highly effective birth control methods, as defined by the investigator, during the study treatment period and for a period of 30 days after the last dose of study drug. A highly effective method of birth control is defined as those that result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.

   -Note: abstinence is acceptable if this is established and preferred contraception for the patient and is accepted as a local standard.
7. Female patients who are breast-feeding should discontinue nursing prior to the first dose of study treatment and until 30 days after the last dose of study drug.
8. Male patients should agree to not donate sperm during the study and for a period of at least 30 days after last dose of study drug
9. Absence of any condition hampering compliance with the study protocol and follow- up schedule; those conditions should be discussed with the patient before registration in the trial.

   * The following adequate organ function laboratory values must be met:

Hematological:

* Absolute neutrophil count (ANC) \>1.5 x109/L
* Platelet count \>100 x109/L
* Hemoglobin \>9 g/dL (may have been transfused)

Renal:

o Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)

Hepatic:

* Total serum bilirubin \<2x ULN
* AST and ALT \<2.5x ULN (or ≤ 5 x ULN for subjects with documented metastatic disease to the liver)

Exclusion Criteria:

1. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
2. Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
3. Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (CTCAE v5 Grade ≥ 3).
4. Other severe acute or chronic medical conditions or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Where this trial is running

Edmonton, Alberta

• Cross Cancer Institute — Edmonton, Alberta, Canada (Recruiting)

Conditions Immune-related Adverse Event; Diarrhea; Advanced Melanoma; Advanced Rectal Carcinoma