Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Circulating Tumour Cells in Somatuline Autogel Treated NeuroEndocrine Tumours Patients (CALM-NET)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02075606
Recruitment Status : Completed
First Posted : March 3, 2014
Results First Posted : June 7, 2019
Last Update Posted : June 7, 2019
Sponsor:
Information provided by (Responsible Party):
Ipsen

Brief Summary:

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
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


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. 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.


  2. 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.



Secondary Outcome Measures :
  1. 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.


  2. 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.

  3. 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.


  4. 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.

  5. 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.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Provision of written informed consent prior to any study related procedures.
  • Patients (either sex) must be 18 years or older.
  • Patients must be suffering from symptoms of diarrhoea and/or flushing at the time of study enrolment.
  • Patients must have a documented diagnosis of a functioning midgut NET.
  • In order to avoid patients with rapidly progressing tumours, only patients with well or moderately differentiated tumours and with a Ki67 proliferation index of <20% will be recruited.
  • The clinically appropriate treatment for the patient must be therapy with a somatostatin analogue.
  • Patients must have had either a positive somatostatin receptor scintigraphy result or a positive 68Gallium-DOTATATE PET imaging result.

Exclusion Criteria:

  • If the patient is at risk of pregnancy or is breast feeding, unless treatment with Somatuline Autogel is clearly needed (as determined by the clinician).
  • The patient is, in the opinion of the investigator, unable to comply fully with the protocol and the study instructions, or present any concomitant condition which could compromise the objectives of the study and/or preclude the protocol-defined procedures (e.g. severe medical conditions, brain metastases, psychiatric disorders, active or uncontrolled infection, known pituitary disease).
  • The patient has been treated with any other unlicensed drug within the last 30 days before study entry or will require a concurrent treatment with any other experimental drugs or treatments.
  • The patient has been treated with a somatostatin analogue prior to study entry, unless a washout period of at least 2 weeks for subcutaneous octreotide, or at least 6 weeks for a single dose of long acting somatostatin analogue has occurred.
  • The patient has received interferon, chemotherapy, chemoembolisation or radionuclide therapy within 3 months prior to study entry.
  • The patient has a history of hypersensitivity to drugs with a similar chemical structure.
  • Females of childbearing potential must be using oral, double barrier or injectable contraception. Non childbearing potential is defined as being post-menopause for at least 1 year, surgical sterilisation or hysterectomy at least three months before the start of the study.
  • The patient has abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the Investigator, might jeopardise the patient's safety or decrease the chance of obtaining satisfactory data needed to achieve the objective(s) of the study.

Information from the National Library of Medicine

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


Locations
Layout table for location information
United Kingdom
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
Hammersmith Hospital
London, United Kingdom
King's College Hospital
London, United Kingdom
Royal Free Hospital
London, United Kingdom
Maidstone Hospital
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
Sponsors and Collaborators
Ipsen
Investigators
Layout table for investigator information
Study Director: Matthew Hickling, MD Ipsen
  Study Documents (Full-Text)

Documents provided by Ipsen:
Statistical Analysis Plan  [PDF] September 15, 2017
Study Protocol  [PDF] October 27, 2015


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Ipsen
ClinicalTrials.gov Identifier: NCT02075606     History of Changes
Other Study ID Numbers: A-97-52030-270
2013-002194-22 ( EudraCT Number )
First Posted: March 3, 2014    Key Record Dates
Results First Posted: June 7, 2019
Last Update Posted: June 7, 2019
Last Verified: February 2019
Keywords provided by Ipsen:
NET
Symptomatic response
Functioning NeuroEndocrine Tumours
midgut region
Additional relevant MeSH terms:
Layout table for MeSH terms
Neuroendocrine Tumors
Neoplasms
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Neoplasm Metastasis
Neoplastic Cells, Circulating
Neoplastic Processes
Pathologic Processes
Lanreotide
Angiopeptin
Somatostatin
Antineoplastic Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs