Telotristat Ethyl for Neuroendocrine Tumors

Overseen By Cezar A. Iliescu, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: M.D. Anderson Cancer Center

Must be taking: Somatostatin analogs

Must not be taking: Everolimus, Chemotherapy

Disqualifiers: Pregnancy, Cardiac arrhythmia, Hepatitis, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 1

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether telotristat ethyl, combined with the standard somatostatin analog therapy, better manages symptoms of neuroendocrine tumors that have metastasized. The focus is on improving conditions like carcinoid syndrome and heart problems linked to these tumors. Participants will receive either the new treatment combination or standard care to determine which is more effective. Those with neuroendocrine tumors that have spread and a history of carcinoid syndrome, while on stable somatostatin therapy, may be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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

The trial requires participants to be on a stable dose of somatostatin analog therapy for at least 2 months before joining. It doesn't specify if you need to stop other medications, so it's best to discuss your current medications with the trial team.

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

Research shows that telotristat ethyl is generally safe for patients with neuroendocrine tumors. Studies have found that combining telotristat ethyl with other treatments remains safe. No reports of serious side effects have emerged that would make it unsafe for most people. However, some individuals might experience mild side effects, such as nausea or changes in bowel habits. Overall, the treatment is considered safe, allowing most people to use it without major problems. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Telotristat ethyl is unique because it targets serotonin production in neuroendocrine tumors, which is different from the standard treatments like somatostatin analogs that primarily focus on hormone suppression. This novel approach helps reduce the debilitating diarrhea often associated with these tumors, potentially improving patients' quality of life significantly. Researchers are excited about telotristat ethyl because it offers a new mechanism of action that complements existing therapies, providing a more comprehensive treatment strategy for managing neuroendocrine tumors.

What evidence suggests that telotristat ethyl might be an effective treatment for neuroendocrine tumors?

Studies have shown that telotristat ethyl can help manage symptoms of carcinoid syndrome, often linked to certain types of tumors. Earlier research indicated that patients experienced stable or improved symptoms after using telotristat ethyl. Another study found that many patients expressed satisfaction with their treatment after six months. Evidence also suggests that telotristat ethyl might slow tumor growth by affecting serotonin levels, which influence tumor development. In this trial, one group of participants will receive telotristat ethyl alongside SSA, while another group will receive a placebo with SSA. Overall, these findings suggest that telotristat ethyl could benefit patients with metastatic tumors. ^{4 6 7 8 9}

Who Is on the Research Team?

Cezar Iliescu, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults (18+) with metastatic neuroendocrine tumors and carcinoid syndrome, currently on stable somatostatin analog therapy. They must be able to consent, use effective contraception if of childbearing potential, and have an ECOG performance status of 0-2. Exclusions include prior telotristat ethyl use within 3 months, significant cardiac issues, severe liver or kidney impairment, pregnancy/lactation, short life expectancy (<6 months), recent other cancer treatments or investigational drugs.

Inclusion Criteria

I agree to use birth control during and for 30 days after the study.

I am taking the highest dose of SSA therapy that I can tolerate.

I am capable of becoming pregnant because I have not been sterilized and am not postmenopausal.

Exclusion Criteria

My heart condition won't risk my safety or affect the study's results.

I am taking everolimus because my previous treatment didn't work well.

Your doctor thinks you have less than 6 months to live.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive telotristat ethyl or placebo and somatostatin analog therapy for 6 months

6 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Telotristat Ethyl

Trial Overview This phase III trial is testing whether adding telotristat ethyl to standard somatostatin analog therapy is more effective than the standard therapy alone in controlling symptoms and heart disease related to carcinoid syndrome in patients with metastatic neuroendocrine tumors.

How Is the Trial Designed?

Group I: Arm A (telotristat ethyl, SSA) Experimental Treatment 2 Interventions

Patients receive telotristat ethyl PO TID and SSA for 6 months in the absence of disease progression or unacceptable toxicity.

Group II: Arm B (placebo, SSA) Active Control 2 Interventions

Patients receive placebo PO TID and SSA for 6 months in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

TerSera Therapeutics LLC

Industry Sponsor

Trials

11

Recruited

1,300+

Published Research Related to This Trial

In the phase 3 NETTER-1 trial involving 231 patients with advanced midgut neuroendocrine tumors, the addition of 177Lu-Dotatate to long-acting octreotide did not significantly improve overall survival compared to high-dose long-acting octreotide alone, with median overall survival times of 48.0 months versus 36.3 months, respectively.

Long-term safety results showed that only 3% of patients in the 177Lu-Dotatate group experienced serious treatment-related adverse events, and no new safety concerns were identified during follow-up, indicating that the treatment has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177Lu-Dotatate plus long-acting octreotide versus high&#8209;dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial. Strosberg, JR., Caplin, ME., Kunz, PL., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9575469/

Real-World Clinical and Patient-Reported Outcomes from the ... This longitudinal observational study showed improvements in real-world clinical and humanistic outcomes for patients with CS and at least 6 months of TE ...

2. jhoponline.com jhoponline.com/special-issues/2020-year-in-review-neuroendocrine-tumors/efficacy-of-telotristat-ethyl-in-patients-with-progressive-net-disease-real-world-clinical-practice-experience

Efficacy of Telotristat Ethyl in Patients with Progressive NET ... All patients exhibited stabilization or improvement in ≥1 physician-assessed post-TE CS symptoms from baseline. Significant improvements were noted in nearly ...

3. xermelo.com xermelo.com/hcp/efficacy

Efficacy | XERMELO® (telotristat ethyl) 6-month results among patients taking XERMELO included: somewhat to very satisfied (78%), neither satisfied nor dissatisfied (10%), somewhat dissatisfied (9%), ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.e16205

Telotristat ethyl with PRRT in the treatment of well ... Most patients received PRRT as 3rd line therapy. 59 (88%) in the entire cohort and 17 (74%) in the telotristat group received 4 doses of PRRT.

5. tandfonline.com tandfonline.com/doi/full/10.2147/CMAR.S261257

Full article: Antiproliferative Effects of Telotristat Ethyl in Patients ... TE may have antitumor effects consistent with serotonin overproduction in tumor growth. Keywords: neuroendocrine tumors · carcinoid tumor · malignant carcinoid ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6693702/

Long‐Term Safety Experience with Telotristat Ethyl Across ... The median overall survival in patients with localized NETs is >30 years, whereas in patients with regional NETs, it is 10.2 years, and for patients with ...

7. theoncologynurse.com theoncologynurse.com/2020-year-in-review-neuroendocrine-tumors/safety-in-patients-with-nets-receiving-telotristat-ethyl-with-peptide-receptor-radionuclide-therapy

Safety in Patients with NETs Receiving Telotristat Ethyl with ... A total of 24 patients who received TE and PRRT were included in the safety analysis; the median age was 64 years (range, 39-78 years). Within 180 days of ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.472

A phase 2, open-label, safety and efficacy study of ... Conclusions: The study did not achieve its primary endpoint of 60% of patients on TE plus GC chemotherapy being alive and progression free at 6 ...

9. ww.nanets.net ww.nanets.net/abstracts-archive/2018/894-abstract-c22/file

C-22 Safety Analysis of Patients with. Neuroendocrine Tumors (NETs). Receiving Concomitant Treatment with Telotristat Ethyl (TE) and. Everolimus (EVE) in Phase 3.