Circulating Tumour Cells in Somatuline Autogel Treated NeuroEndocrine Tumours Patients (CALM-NET)
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|ClinicalTrials.gov Identifier: NCT02075606|
Recruitment Status : Completed
First Posted : March 3, 2014
Results First Posted : June 7, 2019
Last Update Posted : June 7, 2019
Circulating tumour cells (CTCs) are detectable in the blood in around 50% of patients with functioning NeuroEndocrine Tumours (NET) arising in the midgut area (tumours which are secreting hormones and are located in the area in the middle of the digestive system) and their presence usually means that the prognosis for the patient is poor. CTCs have also been shown to be valuable as predictive markers following treatment and there is increasing interest in using CTCs as 'liquid biopsies' that can help to inform treatment decisions. CTC analysis has the benefit of being relatively non- invasive and quick compared with a conventional CT scan and is therefore an attractive method of monitoring the tumour throughout the treatment period.
The purpose of this study is to assess the clinical value that enumeration will have in predicting the clinical symptomatic response and progression free survival in patients receiving Somatuline Autogel for functioning midgut NETs over a one year period.
|Condition or disease||Intervention/treatment||Phase|
|NeuroEndocrine Tumours||Drug: lanreotide acetate||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase IV, Multicentre, Open Label, Single Group Exploratory Study to Assess the Clinical Value of Enumeration of Circulating Tumour Cells (CTCs) to Predict Clinical Symptomatic Response and Progression Free Survival in Patients Receiving Deep Subcutaneous Administrations of Somatuline® (Lanreotide) Autogel® to Treat the Symptoms of Functioning Midgut NeuroEndocrine Tumours (NET)|
|Study Start Date :||May 2014|
|Actual Primary Completion Date :||June 2017|
|Actual Study Completion Date :||June 2017|
Experimental: Somatuline Autogel®
Somatuline Autogel® to treat Functioning Midgut NeuroEndocrine Tumours (NET)
Drug: lanreotide acetate
Somatuline Autogel injection 120mg for first 3 months then 120, 90 or 60 mg administered via the deep subcutaneous route every 28 days
- Assessment of Clinical Symptomatic Response [ Time Frame: From baseline up to Week 53. ]
This endpoint was assessed using 2 efficacy variables:
- CTCs, enumerated at baseline and Weeks 5, 17, 25, 53
- Clinical symptomatic response, assessed by the use of symptom reporting
Subjects recorded 24-hour symptom frequency and severity for 7 days prior to first treatment (baseline), throughout the study, and up to 28 days following final drug administration. Symptoms were recorded by answering predetermined questions on the interactive voice response system (IVRS).
Subjects were considered to have a clinical symptomatic response between baseline and last study visit if any 1 of the following criteria were fulfilled: the average number of episodes of diarrhoea decreased by at least 50%, the average number of episodes of flushing decreased by at least 50%, the mode severity of flushing decreased by at least 1 level. Clinical symptomatic response was assessed as a qualitative variable (Yes/No) and reported according to CTC presence at baseline and overall.
- Percentage of Subjects With Time Point Responses According to Response Evaluation Criteria in Solid Tumours (RECIST) Assessments at Weeks 25 and 53 [ Time Frame: Week 25 and Week 53. ]
Subjects underwent Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scans at baseline, Visit 8 (Week 25) and Visit 15 (Week 53). Progression was assessed by investigators using RECIST v1.1, and classified as a complete response, partial response, stable disease, progressive disease or non evaluable.
The time point responses at Week 25 and Week 53 were analysed by CTC presence at baseline and overall. The percentage of subjects within each response category are presented. Percentages are based on the number of subjects in the concerned population with available responses.
- Mean Change From Baseline in Number of Episodes of Diarrhoea and Flushing [ Time Frame: From baseline up to Week 53. ]
The effect of lanreotide Autogel on the symptoms of diarrhoea and flushing in subjects was assessed through subject reporting of symptoms every 24-hours for the 7 days prior to treatment (baseline), for the first 16 weeks and on days 11 to 17 after each subsequent injection interval. After the final study drug injection at Week 49, subjects provided 24-hour symptom frequency on days 11 to 28 (up to Week 53). Symptom frequency was recorded by answering predetermined questions on the IVRS.
Mean change from baseline in frequency (number of episodes) of diarrhoea and flushing are described at Visit 2 (average number of episodes in Week 1) and at Visit 14 (average number of episodes over days 11 to 17 after Week 49 injection and over days 11 to 28 after Week 49 injection) by CTC presence at baseline and overall. A negative change indicates an improvement in symptoms from baseline.
- Mode Symptom Severity of Episodes of Flushing [ Time Frame: From baseline up to Week 53. ]The effect of lanreotide Autogel on the mode severity of flushing was assessed through subject reporting of symptoms every 24-hours for the 7 days prior to treatment (baseline), for the first 16 weeks and on days 11 to 17 after each subsequent injection interval until Week 49. After the final study drug injection at Week 49, subjects provided 24-hour symptom severity on days 11 to 28 (up to Week 53). Symptom severity was recorded by answering predetermined questions on the IVRS using a three-point system (mild, moderate or severe). The mode (most frequent) intensity of flushing are reported at baseline and at Visit 14 (average number of episodes over days 11 to 17 after Week 49 injection and over days 11 to 28 after Week 49 injection). Percentages of subjects in each severity category are based on the number of subjects in the analysis set with available responses. Data is presented according to CTC presence at baseline and overall.
- Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30 [ Time Frame: From baseline up to Week 53. ]
The effect of lanreotide Autogel treatment on QoL was assessed using the EORTC QLQ-C30 at baseline, Weeks 13 (Visit 5), 25 (Visit 8) and 53 (Visit 15/end of study). The 30 item scale is divided into 9 multi item scales (including 5 functional scales, 1 global health status/QoL scale and 3 general symptom scales) and 6 single items. Possible answers to the first 28 items (all items except the 2 concerning global quality of life) go from 1 (Not at all) to 4 (Very much). The answers for the 2 last questions (Q29- 30) go from 1 (Very poor) to 7 (Excellent). All of the scales and single-item measures range in score from 0 to 100. For multi-item scales, the raw score will be calculated by the addition of item responses divided by the number of items. Higher scores for global health and functional domains indicate a better QoL, while higher symptom scores indicate worse symptoms.
The mean change from baseline at each time point is reported for each of the category subscores.
- QoL Questionnaire: EORTC QLQ-G.I.NET21 [ Time Frame: From baseline up to Week 53. ]The effect of lanreotide Autogel treatment on QoL was assessed using the EORTC QLQ-G.I.NET21 at baseline, Weeks 13 (Visit 5), 25 (Visit 8) and 53 (Visit 15/end of study). The QLQ-G.I.NET21 questionnaire contained 21 questions that used a 4-point scale (1 = Not at all, 2 = A little, 3 = Quite a bit, 4 = Very much) to evaluate 3 defined multi-item symptom scales (endocrine, gastrointestinal and treatment related side effects), 2 single item symptoms (bone/muscle pain and concern about weight loss), 2 psychosocial scales (social function and disease-related worries) and 2 other single items (sexuality and communication). Each individual subscore was transformed to range from 0 to 100. Higher scores indicate worse symptoms or more problems. The mean change from baseline at each time point is reported for each of the category subscores.
- Percentage of Subjects Alive and Progression Free at One Year [ Time Frame: From baseline up to Week 53. ]
Subjects underwent CT or MRI scans at baseline and Week 53. Progression was assessed by investigators using RECIST v1.1. The best overall response to study treatment is the highest time point response achieved by the subject and was assessed as a complete response, partial response, stable disease, progressive disease or non evaluable. For analysis of PFS, event dates were assigned to the first time that progressive disease was noted or the date of death. In case of progressive disease followed by death, the first event was considered in the analysis. Censoring dates were defined in subjects with no progressive disease or death before end of study.
At one year (end of study), the mean percentage of subjects who were alive and progression free, as calculated using the Kaplan-Meier method, is reported by CTC presence and overall.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02075606
|Basingstoke & North Hampshire Hospital|
|Basingstoke, United Kingdom|
|Queen Elizabeth Hospital|
|Birmingham, United Kingdom|
|University Hospital Wales|
|Cardiff, United Kingdom|
|Beatson West of Scotland Cancer Centre|
|Glasgow, United Kingdom|
|St James's University Hospital|
|Leeds, United Kingdom|
|University Hospital Aintree|
|Liverpool, United Kingdom|
|London, United Kingdom|
|King's College Hospital|
|London, United Kingdom|
|Royal Free Hospital|
|London, United Kingdom|
|Maidstone, United Kingdom|
|The Christie Hospital|
|Manchester, United Kingdom|
|Norfolk & Norwich Hospital|
|Norwich, United Kingdom|
|Royal Hallamshire Hospital|
|Sheffield, United Kingdom|
|Southampton University Hospital|
|Southampton, United Kingdom|
|Study Director:||Matthew Hickling, MD||Ipsen|