Carcinoid Heart Disease Clinical Trial
Official title:
Randomized Phase III Clinical Trial of Lanreotide Combined With Telotristat Ethyl or Placebo for the First-line Treatment in Patients With Advanced Well Differentiated Small Intestinal Neuroendocrine Tumours (siNET) With Highly-functioning Carcinoid Syndrome
This is a randomized phase III clinical trial of Lanreotide combined with Telotristat ethyl
or placebo for the first-line treatment in patients with advanced well differentiated small
intestinal neuroendocrine tumours (siNET) with highly-functioning carcinoid syndrome to test
whether telotristat ethyl plus lanreotide is more effective than placebo plus lanreotide in
reducing the number of daily bowel movements.
In addition, the study allows evaluation of the biochemical response (5-HIAA and
chromogranin-A), the reduction in the number of daily cutaneous flushing episodes, the
improvement in abdominal pain/discomfort, health-related quality of life, improvement in
gastro-intestinal and endocrine symptoms, changes in emotional functioning, the impact of
discontinuation of telotristat ethyl/placebo on HRQOL and symptoms, and the safety and
toxicity of the treatment.
Patients will enter into a screening/run-in period of 1 week to establish baseline
characteristics and symptomatology. The baseline assessment of daily bowel movement, as
assessed in an electronic diary, will be averaged over the run-in period.
Following the screening/run-in period, patients will be randomly assigned (1:1) to either the
control arm or the experimental arm for 12 months. Randomization will be stratified according
to the grade of tumour differentiation (grade 1 vs. grade 2) and by baseline number of bowel
movements per day (4-6 versus >6). A total of 94 patients will be randomly assigned (1:1) to
either arm.
Upon randomization, all patients will enter the 12-month treatment period with lanreotide +
telotristat ethyl/placebo (blinded). In the experimental arm, patients will receive the deep
subcutaneous injection of lanreotide (120 mg) every 28 days and 250 mg orally three times
daily (TID) of telotristat ethyl for 12 months. In the control arm, patients will receive the
deep subcutaneous injection of lanreotide every 28 days (120 mg) and placebo orally TID for
12 months.
After completion of a minimum of 6 months on randomized blinded-treatment, the protocol
allows for patients on treatment with telotristat ethyl/placebo to be unblinded in the event
of "lack of symptom control". Unblinding due to "lack of symptom control" can happen at any
time between 6 and 12 months of the blinded-treatment period. After unblinding, patient will
interrupt protocol treatment and will be further treated as per clinician discretion.
All patients will be unblinded after a maximum of 12 months on randomized blinded-treatment.
After a follow-up of 12 months, patients will go off study except patients with carcinoid
heart disease. Patients off study will be further treated as per clinician discretion.
Patients with carcinoid heart disease will continue open-label treatment on study (lanreotide
+ telotristat ethyl or lanreotide alone according to what they were receiving at unblinding
at 12 months) for 4 additional years (open-label extension period). Patients with carcinoid
heart disease who discontinue protocol treatment before 12 months will also enter the
extension period for additional follow-up. Additional follow-up will last 4 years for these
patients and will include 6-monthly cardiological assessments.
All efficacy analyses will be conducted in the Intention-to-treat population as primary
analyses i.e. all 94 randomized patients will be analyzed in the arm they were allocated by
randomization. Safety analyses will be performed on the Safety population i.e. on all
patients who have received at least one dose of the study drugs.
The translational research projects include blood metabolite discovery and targeted assays to
find new biomarker candidates of response to Telotristat.
Human biological material that will be collected for translational research purpose:
- whole blood, plasma and serum at baseline, 4 hours after first dose, 4 weeks, 12 weeks
and at end of treatment visit with telotristat/placebo (due to end of study, disease
progression or lack of benefit)
- archival tissue samples (formalin-fixed paraffin-embedded) will be retrieved for all
patients at study entry. In addition, one EDTA blood tube of whole blood (10 ml) at
baseline, 12 weeks and end of treatment (EOT visit) might be also collected for not yet
pre-defined and further translational research.
Quality of life will be assessed with the EORTC Quality of Life Questionnaire (QLQ-C30)
version 3, together with the QLQ-GI.NET21 specific module designed for Neuroendocrine
Tumours. The computer-adaptive testing (CAT) diarrhea scale will also be used. The baseline
questionnaires must be completed during the screening period and before randomization.
Subsequent questionnaires are completed at 4 weeks, 12 weeks, 24 weeks, 36 weeks and 52
weeks. Once a patient has stopped treatment, HRQoL data collection for that patient is
required 1 month (28-35 days) after protocol treatment discontinuation.
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