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

79 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase III trial compares the effect of telotristat ethyl and the current standard of care somatostatin analog therapy or somatostatin analog therapy alone in treating patients with neuroendocrine tumor that has spread to other places in the body (metastatic). Telotristat ethyl and somatostatin analog therapy may help to control carcinoid syndrome and carcinoid heart disease.

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.

What data supports the effectiveness of the drug Telotristat Ethyl for neuroendocrine tumors?

Research shows that Telotristat Ethyl can help reduce tumor size and improve symptoms like diarrhea and weight loss in patients with neuroendocrine tumors, particularly those with carcinoid syndrome. Studies also indicate that patients maintain or gain weight and improve their nutritional status over long-term treatment. ^{1 2 3 4 5}

Is telotristat ethyl safe for humans?

Telotristat ethyl has been studied in patients with carcinoid syndrome, and the safety data from these studies show that it is generally well tolerated. Most side effects were mild to moderate, with some serious events reported, but these were not common. ^{3 5 6 7 8}

How is the drug Telotristat Ethyl unique for treating neuroendocrine tumors?

Telotristat Ethyl is unique because it is an oral medication that works by inhibiting tryptophan hydroxylase, which reduces serotonin production, helping to manage carcinoid syndrome symptoms like diarrhea when somatostatin analogs alone are not enough. ^{1 3 5 9 10}

Research Team

Cezar Iliescu, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Survival and Clinical Outcomes with Telotristat Ethyl in Patients with Carcinoid Syndrome. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Weight Maintenance up to 48 Weeks in Patients With Carcinoid Syndrome Treated With Telotristat Ethyl: Pooled Data From the Open-Label Extensions of the Phase III Clinical Trials TELESTAR and TELECAST. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Long-Term Treatment with Telotristat Ethyl in Patients with Carcinoid Syndrome Symptoms: Results from the TELEPATH Study. [2022]

4. England 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Time to Sustained Improvement in Bowel Movement Frequency with Telotristat Ethyl: Analyses of Phase III Studies in Carcinoid Syndrome. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Telotristat ethyl in carcinoid syndrome: safety and efficacy in the TELECAST phase 3 trial. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Spotlight on telotristat ethyl for the treatment of carcinoid syndrome diarrhea: patient selection and reported outcomes. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Budgetary Impact of Telotristat Ethyl, a Novel Treatment for Patients with Carcinoid Syndrome Diarrhea: A US Health Plan Perspective. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Telotristat ethyl: a new option for the management of carcinoid syndrome. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Understanding the Patient Experience with Carcinoid Syndrome: Exit Interviews from a Randomized, Placebo-controlled Study of Telotristat Ethyl. [2019]