SER-155 for Diarrhea

Recruiting at 6 trial locations

Overseen By David Faleck, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Steroids, Infliximab, Vedolizumab, Ustekinumab

Disqualifiers: Active GI infection, Inflammatory bowel disease, Severe neutropenia, others

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

Compensation: Varies

Number of Visits: 15

Duration: 6 weeks

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called SER-155 for individuals with diarrhea caused by immune checkpoint inhibitors, which are medications that help the immune system fight cancer. The main goal is to determine if SER-155 is safe and causes only mild side effects when used as an initial treatment. It targets those experiencing significant diarrhea and related symptoms who have not yet received other treatments for this condition. Participants should have recently undergone immune checkpoint inhibitor therapy and be able to take oral medication. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain immunosuppressive therapies or investigational medications for diarrhea/colitis within 30 days before joining the trial.

Is there any evidence suggesting that SER-155 is likely to be safe for humans?

Research shows that SER-155 is undergoing testing to determine its safety for individuals with diarrhea caused by immune checkpoint inhibitors, a type of cancer treatment. While specific safety data from the studies is not yet available, its early testing phase (Phase 1) indicates that researchers are primarily assessing its safety. This phase involves closely monitoring any side effects. As SER-155 remains in the early stages of testing, there is insufficient information on its tolerability. Trial participants will contribute to gathering this crucial safety information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for immune checkpoint inhibitor-related enterocolitis, which often involve immunosuppressive therapies, SER-155 offers a unique approach. This treatment is derived from live bacteria, aiming to restore balance in the gut microbiome, which is often disrupted in these patients. Researchers are excited about SER-155 because it targets the gut environment directly, potentially reducing inflammation and improving symptoms without the side effects associated with traditional immunosuppressive drugs.

What evidence suggests that SER-155 might be an effective treatment for irEC?

Research shows that SER-155 is being tested in this trial as a new treatment for diarrhea caused by certain cancer treatments. These treatments, known as immune checkpoint inhibitors, can sometimes lead to diarrhea and inflammation in the colon, called enterocolitis. Although limited data exists on SER-155's effectiveness, it is designed to help by potentially restoring balance in the gut. Early signs are promising, as the treatment aims to reduce side effects while addressing the root problem. Ongoing research in this trial will provide more information about its safety and effectiveness for this condition. ^{2 3 4 6 7}

Who Is on the Research Team?

David Faleck, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 who've had immunotherapy in the last 6 months can join this trial if they have moderate diarrhea likely caused by the treatment. They must be able to take pills, agree to use birth control for a month after the study, and sign a consent form. People with active gut infections, high steroid doses for other side effects, recent experimental diarrhea treatments, hospitalization for gut issues or severe immune system problems can't participate.

Inclusion Criteria

I am older than 18 years.

I am currently receiving chemotherapy or other cancer treatments.

I have moderate to severe diarrhea from immunotherapy, possibly with mild to moderate colitis symptoms.

Exclusion Criteria

I do not have an active infection in my digestive system.

I am taking more than 10 mg of prednisone daily for a non-GI side effect.

Any condition that may increase the risk of study participation and/or interfere with the interpretation of study results

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SER-155 for the treatment of immunotherapy-related enterocolitis

6 weeks

Visits at day 15 and day 43

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• SER-155

Trial Overview

The trial is testing SER-155 as a potential first-line treatment for diarrhea resulting from immune checkpoint inhibitor therapy (irEC). The goal is to determine its safety and whether it causes only mild or few side effects in patients suffering from irEC.

How Is the Trial Designed?

Group I: Participants with Immune checkpoint inhibitor-related enterocolitis (irEC) Experimental Treatment 1 Intervention

Participants with grade 2-3 diarrhea from irEC who have not yet received immunosuppressive therapy for irEC

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

Intraperitoneal administration of L-5-hydroxytryptophan (L-5-HTP) in mice significantly increases defecation, indicating its potential role in inducing diarrhea, particularly in conditions like carcinoid syndrome.

The effectiveness of L-5-HTP in causing diarrhea is dependent on its conversion to serotonin (5-HT), and specific 5-HT antagonists, especially 5-HT3 type, can effectively reduce this diarrhea, suggesting a targeted approach for managing symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-HTP induced diarrhea as a carcinoid syndrome model in mice? Bourin, M., Hascoet, M., Deguiral, P.[2019]

In a study of 29 patients with chemotherapy-induced diarrhea (CID), monthly injections of long-acting octreotide (30 mg) led to a significant reduction in diarrhea severity for 41% of participants who completed the study, allowing them to continue chemotherapy at full doses.

While octreotide showed promise in managing CID, further research is needed to determine its optimal dosage and effectiveness when used alongside other antidiarrheal treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting octreotide as secondary prevention of chemotherapy-induced diarrhea: proof of concept. VAN DEN Heuvel, B., Peeters, M., Hendlisz, A., et al.[2019]

5-aminosalicylic acid (5-ASA) was found to be significantly more effective than placebo in treating active ulcerative colitis, with a pooled odds ratio of 0.39 indicating a lower failure rate in achieving clinical improvement or remission.

While 5-ASA showed better tolerability compared to sulfasalazine (SASP) in active disease, there was insufficient evidence to confirm its superiority over SASP for maintenance therapy, with a pooled odds ratio of 1.29 indicating a higher failure rate to maintain remission compared to SASP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternatives to Sulfasalazine: A Meta-analysis of 5-ASA in the Treatment of Ulcerative Colitis. Sutherland, LR., Roth, DE., Beck, PL.[2018]

In a study of 30 patients with distal ulcerative colitis, those treated with 5-aminosalicylic acid (5-ASA) suppositories had a significantly higher remission rate of 92% after one year compared to only 21% in the placebo group.

The treatment was found to be safe, with no side effects reported, indicating that 5-ASA is an effective option for maintaining remission in patients with distal ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-Aminosalicylic acid suppositories in the maintenance of remission in idiopathic proctitis or proctosigmoiditis: a double-blind placebo-controlled clinical trial. D'Arienzo, A., Panarese, A., D'Armiento, FP., et al.[2013]

The 5-HT3-receptor antagonist KB-R6933 effectively inhibited diarrhea induced by serotonin (5-HT) in mice, suggesting its potential as a treatment for certain types of diarrhea.

KB-R6933 also reduced intestinal fluid secretion stimulated by cholera toxin in rats, indicating its broader therapeutic potential in managing diarrhea-related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the 5-hydroxytryptamine3 (5-HT3)-receptor antagonist KB-R6933 on experimental diarrhea models. Ozaki, A., Yoshidomi, M., Sukamoto, T.[2022]

In a study of 409 female patients with irritable bowel syndrome with diarrhea (IBS-D), a dose of 2.5 μg of ramosetron significantly improved abdominal pain and discomfort over three months compared to placebo.

While ramosetron was effective in reducing IBS symptoms, it also caused more constipation than placebo, indicating a need to balance efficacy with potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal dose of ramosetron in female patients with irritable bowel syndrome with diarrhea: A randomized, placebo-controlled phase II study. Fukudo, S., Matsueda, K., Haruma, K., et al.[2018]

In a study of 104 children aged 6 months to 16 years with acute gastroenteritis, a single oral dose of ondansetron significantly reduced the duration of symptoms caused by rotavirus, with a median reduction of two days.

Ondansetron also decreased the number of diarrhea episodes, especially in children who had been ill for more than three days, suggesting it may help improve recovery and reduce the need for hospitalization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ondansetron treatment reduces rotavirus symptoms-A randomized double-blinded placebo-controlled trial. Hagbom, M., Novak, D., Ekström, M., et al.[2018]

Cilansetron, a 5-HT3 receptor antagonist, has shown significant efficacy in treating diarrhea-predominant irritable bowel syndrome (IBS), with two large trials demonstrating superior symptom relief compared to placebo over 3 and 6 months.

While cilansetron can induce constipation in some patients, serious adverse effects were rare, with only four cases of transient ischemic colitis reported among 1484 participants, indicating a generally favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cilansetron in the treatment of diarrhea-predominant irritable bowel syndrome? Stacher, G.[2012]

In a case study of an infant with severe refractory secretory diarrhea of uncertain cause, the somatostatin analogue SMS 201-995 significantly reduced stool output from 250 ml/kg/day to 80-100 ml/kg/day, demonstrating its efficacy in managing this condition.

The treatment with SMS 201-995 was well-tolerated over 9 months, with no observed metabolic, hormonal, or growth abnormalities, indicating its safety for use in this young patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of idiopathic secretory diarrhea of infancy with the somatostatin analogue SMS 201-995. Jaros, W., Biller, J., Greer, S., et al.[2019]

In a case study of a patient with acute postoperative secretory diarrhea following bowel obstruction, the somatostatin analogue SMS 201-995 significantly reduced colostomy output and normalized intestinal abnormalities, indicating its efficacy in managing this condition.

The patient's diarrhea was linked to abnormal secretion in the small intestine, and SMS 201-995 effectively addressed this issue, suggesting it could be a valuable treatment for similar postoperative complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe posthemicolectomy diarrhea: evaluation and treatment with SMS 201-995. Sharkey, MF., Kadden, ML., Stabile, BE.[2019]

In a study of 15 patients with chemotherapy-induced diarrhoea, acetorphan significantly reduced the average number of stools per day from 6.3 to 4.9, indicating its potential efficacy in managing this side effect of chemotherapy.

Acetorphan also decreased the number of days with liquid stools from 4.7 to 2.4, suggesting it may help alleviate severe diarrhoea without causing constipation, warranting further investigation in a randomized controlled trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of acute chemically induced diarrhea by inhibition of enkephalinase. Results of a pilot study]. Dorval, ED., Regimbeau, C., Gamelin, E., et al.[2013]

Cilansetron, a new medication for irritable bowel syndrome (IBS) with diarrhea, has shown significant efficacy in relieving symptoms in both male and female patients during phase III trials.

The drug is generally well tolerated, with the most common side effect being constipation in 3-12% of patients, and while there have been some cases of ischemic colitis, these were self-limited and did not require surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cilansetron. Olden, KW., Crowell, MD.[2017]

Cilansetron, a 5-HT3 receptor antagonist, has shown effectiveness in improving symptoms of irritable bowel syndrome with diarrhea predominance (IBS-D) in both male and female patients, outperforming placebo in two large Phase III clinical trials.

While cilansetron is generally well tolerated, it has a rare but concerning side effect of suspected ischemic colitis, occurring at a rate of 3.77 per 1000 person-years, which is higher than expected in the IBS population. All reported cases have resolved without serious complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cilansetron: a new serotonergic agent for the irritable bowel syndrome with diarrhoea. Chey, WD., Cash, BD.[2019]

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