Study to Assess the Efficacy and Safety of Different Doses of BIM 23A760 in Patients With Carcinoid Syndrome

Study Overview
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Brief Summary
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The purpose of the protocol is to assess the efficacy and safety of BIM 23A760 on patient's overall satisfaction in terms of symptom relief (diarrhoea and/or flushes) in patients with carcinoid syndrome after 24 weeks of treatment.

Official Title
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Phase II, Open, Adaptive, Dose Escalating, Multicentre Titration Study to Assess the Efficacy and Safety of Repeated Subcutaneous Administration of Different Doses of BIM 23A760 in Patients With Carcinoid Syndrome

Conditions
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Carcinoid Syndrome

Intervention / Treatment
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* Drug: BIM 23A760


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient has a carcinoid syndrome defined as ≥3 stools/day and/or ≥3 flushes/week. The patient has elevated 5-Hydroxyindoleacetic acid (above upper limit normal). The patient has a well-differentiated mid-gut carcinoid tumour or serotonin secreting tumour of unknown localisation with hepatic metastasis. Exclusion Criteria: The patient has undergone surgery related to a neuroendocrine tumour (NET) within 4 weeks prior to study entry or has surgery planned during the study. The patient has received short acting somatostatin analogues (SSAs) within 2 weeks before study entry or has received short acting SSAs for more than 3 months. The patient has received a radiolabelled SSA at any time before study entry. The patient has received long acting SSAs under certain circumstances. The patient has previously received any specific anti tumour treatment such as chemotherapy, (chemo)embolisation, radiotherapy or interferon in the last 6 months. The patient has signs or symptoms of cardiac insufficiency. The patient has an ejection fraction <40% and/or clinically severe cardiac valvular regurgitation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIM 23A760<br>This dose adaptive study is planned to treat up to 20 patients in each starting dose cohort, with a maximum of three starting dose cohorts. The doses planned to be assessed are 1, 2, 4, 6 and 8 mg, however, the maximum starting dose will be 4 mg. The starting dose of the first cohort will be 1 mg; the first cohort will include at least five patients. After the first fifteen patients have been treated for 4 weeks, the results will be reviewed by a Data Review Committee. An extension phase (Part B) is planned for those subjects completing the initial study and fulfilling specific eligibility criteria (symptoms control, willingness to participate, safety and tolerability). | Drug: BIM 23A760<br>* BIM 23A760 is a solution at a concentration of 5 mg/mL ready for subcutaneous injection. BIM 23A760 dose of 1, 2, 4, 6 and 8 mg can be given to the patient according to a dose escalation and titration process. Patients will receive 24 weekly injections of BIM 23A760 during the treatment period. Patients eligible to continue the extension phase will be administered BIM 23A760 for further 52 weekly injections.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With a Positive Overall Satisfactory Relief of Symptoms (Diarrhoea and/or Flushes) on the Likert Scale | Patient satisfaction based on a Likert scale from 0-5 (0 being not satisfied and 5 being completely satisfied) | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Improvement in Symptoms (Diarrhoea and/or Flushes) |  | Up to week 24 | 
| Change in the Quality of Life (QoL) Assessment |  | Week 24 | 
| Change in 5 Hydroxyindoleacetic Acid (5 HIAA) and Chromogranin A |  | Week 24 | 
| Number of Subjects Reported Adverse Events, Including Any Findings From an Examination of the Injection Site(s) |  | Up to week 26 | 
| Minimum Concentration (Cmin) BIM 23A760 Plasma Levels |  | At 9 timepoints up to 1 week after 24th administration in week 24 | 
| Concentration at 2 Hours Postdose (C2 Hours) BIM 23A760 Plasma Levels |  | At 8 timepoints up to week 24 |