Neuroendocrine Tumors
Conditions
Keywords
NET
Brief summary
This trial will test the hypothesis that Telotristat treatment increases the antitumor efficacy of Lutetium Lu 177 Dotatate therapy in neuroendocrine tumors (NETs).
Detailed description
Neuroendocrine tumors (NETs) are a very heterogeneous group of tumors that develop predominantly in the gastrointestinal and pulmonary systems. Clinical detection and diagnosis are more reliable at late stages when metastatic spread has occurred. Patients with advanced disease may suffer from complications of uncontrolled hormone secretion and usually succumb due to tumor progression. This trial tests the hypothesis that inhibition of serotonin production with Telotristat will lead to cytostatic effects on neuroendocrine tumors and will complement the anti-tumor activity of Lutetium 177 Dotatate. The proposed combination may result in improved treatment efficacy as reflected by improved 20-month progression-free survival (PFS) as compared to historical control.
Interventions
DRUGTelotristat (Low-Dose)
Participants in this group will receive Lutetium Lu 177 Dotate (Lutathera) by IV every 2 months (Q8weeks) for a total of 4 doses. They will also receive oral Telotristat at 750mg per day (250mg TID) for 20 months.
DRUGTelotristat (High-Dose)
Participants in this group will receive Lutetium Lu 177 Dotate (Lutathera) by IV every 2 months (Q8weeks) for a total of 4 doses. They will also receive oral Telotristat at 1500mg per day (500mg TID) for 20 months.
Sponsors
TerSera Therapeutics LLC
Lowell Anthony, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Metastatic, or unresectable, histologically confirmed well-differentiated grade 1 and 2 neuroendocrine tumor with a positive gallium 68 Dotatate scan within 6 months prior to study enrollment * Baseline CT scan or MRI with measurable progressive disease based on RECIST Criteria * Failure of at least one prior systemic cancer treatment for this diagnosis * Recovered from Adverse Events of previously administered therapeutic agents to Grade 2 or less toxicity according to CTCAE version 5.0 * Eastern Cooperative Oncology Group (ECOG) performance status ≤2 * normal organ and marrow function
Exclusion criteria
* Prior exposure to Lutetium Lu 177 Dotatate * History of allergic reactions attributed to compounds of similar chemical or biologic composition to Telotristat or Lutetium Lu 177 Dotatate. * Presence of unstable angina or myocardial infarction * New York Heart Association (NYHA) Class III or IV heart failure * uncontrolled angina * history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities * Pregnant or lactating women * Women of childbearing potential or male patients of reproductive potential * Any other significant medical or psychiatric condition, currently uncontrolled by treatment, which may interfere with completion of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | 20 months | Progression-free survival at 20 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | 6 and 12 months | Overall response rate using RECIST v1.1 at 6 and 12 months after therapy |
| Median Progression-Free Survival (PFS) | 36 month | Median progression-free survival. |
| Urinary 5-HIAA | Baseline and 12 months | Levels of urinary 5-Hydroxyindoleacetic acid (5-HIAA) will be measured at baseline and 12 months. |
| Quality of Life (QLQ-C30) | 20 month | The Quality of Life Questionnaire C30 (QLQ-C30) was developed by the European Organization for Research and Treatment of Cancer (EORTC) to assess quality of life in cancer patients.It includes five function domains (physical, emotional, social, role, cognitive), eight symptoms (fatigue, pain, nausea/vomiting, constipation, diarrhea, insomnia, dyspnea, and appetite loss), as well as global health/quality-of-life and financial impact. Subjects respond on a four-point scale from not at all to very much for most items.Raw scores are linearly converted to a 0-100 scale with higher scores reflecting higher levels of function and higher levels of symptom burden. |
| Quality of Life (QLQ-GI.NET21) | 20 month | The Quality of Life GI Neuroendocrine Tumor survey (QLQ-GINET21) contains a total of 21 items: four single-item assessments relating to muscle and/or bone pain (MBP), body image (BI), information (INF) and sexual functioning (SX), together with 17 items organised into five proposed scales: endocrine symptoms (ED; three items), GI symptoms (GI; five items), treatment-related symptoms (TR; three items), social functioning (SF) and disease-related worries (DRW; three items). The response format of the questionnaire is a four-point Likert scale. Responses are linearly transformed to a 0-100 scale using EORTC guidelines, with higher scores reflecting more severe symptoms. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: Low-Dose Telotristat Participants in this group will receive 750mg Telotristat per day.
Telotristat (Low-Dose): Participants in this group will receive Lutetium Lu 177 Dotate (Lutathera) by IV every 2 months (Q8weeks) for a total of 4 doses. They will also receive oral Telotristat at 750mg per day (250mg TID) for 20 months. | 1 |
| Arm 2: High-Dose Telotristat Participants in this group will receive 1500mg Telotristat per day.
Telotristat (High-Dose): Participants in this group will receive Lutetium Lu 177 Dotate (Lutathera) by IV every 2 months (Q8weeks) for a total of 4 doses. They will also receive oral Telotristat at 1500mg per day (500mg TID) for 20 months. | 0 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Company cancelled study | 1 | 0 |
Baseline characteristics
| Characteristic | Arm 1: Low-Dose Telotristat | Total |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants |
| Region of Enrollment United States | 1 participants | 1 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Progression-Free Survival (PFS)
Progression-free survival at 20 months.
Time frame: 20 months
Population: One participant was enrolled in this study. Due to the possibility that participants could reasonably be identified due to low enrollment, data cannot be presented.
Secondary
Median Progression-Free Survival (PFS)
Median progression-free survival.
Time frame: 36 month
Population: One participant was enrolled in this study. Due to the possibility that participants could reasonably be identified due to low enrollment, data cannot be presented.
Secondary
Overall Response Rate (ORR)
Overall response rate using RECIST v1.1 at 6 and 12 months after therapy
Time frame: 6 and 12 months
Population: One participant was enrolled in this study. Due to the possibility that participants could reasonably be identified due to low enrollment, data cannot be presented.
Secondary
Quality of Life (QLQ-C30)
The Quality of Life Questionnaire C30 (QLQ-C30) was developed by the European Organization for Research and Treatment of Cancer (EORTC) to assess quality of life in cancer patients.It includes five function domains (physical, emotional, social, role, cognitive), eight symptoms (fatigue, pain, nausea/vomiting, constipation, diarrhea, insomnia, dyspnea, and appetite loss), as well as global health/quality-of-life and financial impact. Subjects respond on a four-point scale from not at all to very much for most items.Raw scores are linearly converted to a 0-100 scale with higher scores reflecting higher levels of function and higher levels of symptom burden.
Time frame: 20 month
Population: One participant was enrolled in this study. Due to the possibility that participants could reasonably be identified due to low enrollment, data cannot be presented.
Secondary
Quality of Life (QLQ-GI.NET21)
The Quality of Life GI Neuroendocrine Tumor survey (QLQ-GINET21) contains a total of 21 items: four single-item assessments relating to muscle and/or bone pain (MBP), body image (BI), information (INF) and sexual functioning (SX), together with 17 items organised into five proposed scales: endocrine symptoms (ED; three items), GI symptoms (GI; five items), treatment-related symptoms (TR; three items), social functioning (SF) and disease-related worries (DRW; three items). The response format of the questionnaire is a four-point Likert scale. Responses are linearly transformed to a 0-100 scale using EORTC guidelines, with higher scores reflecting more severe symptoms.
Time frame: 20 month
Population: One participant was enrolled in this study. Due to the possibility that participants could reasonably be identified due to low enrollment, data cannot be presented.
Secondary
Urinary 5-HIAA
Levels of urinary 5-Hydroxyindoleacetic acid (5-HIAA) will be measured at baseline and 12 months.
Time frame: Baseline and 12 months
Population: One participant was enrolled in this study. Due to the possibility that participants could reasonably be identified due to low enrollment, data cannot be presented.