Neuroendocrine TumorsNCT05268952
A Study to Evaluate the Value of Circulating Tumour DNA in Follow-up of Patients With an Advanced Gastroenteropancreatic or Lung Neuroendocrine Tumour Under Everolimus +- SSA Treatment (Liquid-NET 2.0)
A study testing Liquid biopsies and Scans (CT, gallium-68 DOTATE/TOC/NOC PET-CT) in people with Neuroendocrine Tumors, run by University Hospital, Antwerp at 3 sites in 2 countries.
Trial summary
Prospective, multicentric, single arm, POC study to evaluate the value of CtDNA in follow-up of patients treated with everolimus, with or without somatostatin analogues for advanced gastroenteropancreatic or lung neuroendocrine tumours. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neuroendocrine Tumors
- What is being tested?
- Liquid biopsies and Scans (CT, gallium-68 DOTATE/TOC/NOC PET-CT)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 27 May 2019to 31 Dec 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years
- Written informed consent prior to any study-related procedure
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Histological proven diagnosis of a well or moderately differentiated GEP-NET (WHO2017 grade 1,2,3 neuroendocrine tumour)
- Documented progressive gastroenteropancreatic or lung neuroendocrine tumour by means of imaging and based upon the RECIST 1.1 criteria and/or PERCIST 1.0 criteria (if available) for which the treating physician has decided to treat with everolimus ± SSA treatment
- Presenting a positive CT and/or DOTANOC scan (at physician's discretion) at study entry with a measurable tumour lesion > 1 cm (CT scan with a maximum slice thickness of 5 mm); baseline CT and/or DOTANOC scan performed up to 28 days prior start of treatment NO previous treatment with everolimus
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- Adequate bone marrow and coagulation function as shown by:
- Haemoglobin ≥ 9.0 g/dL
- ANC ≥ 1,500/mm3 (≥1.5 x 109/L)
- Platelets ≥ 100,000/mm3 (≥ 100x 109/L)
- INR ≤ 2.0
- Adequate liver function as shown by:
- Alanine aminotransferase and aspartate aminotransferase ≤2.5xULN (Upper limit of normal) (or ≤ 5 if hepatic metastases are present)
- Total serum bilirubin ≤ 1.5 x ULN (≤ 3 ULN for patients known to have Gilbert Syndrome)
- Adequate renal function as shown by Serum creatinine≤ 1.5 x ULN
- Fasting serum cholesterol, triglycerides and glucose
- Fasting serum cholesterol ≤ 300 mg/dL or 7.75 mmol/L
- Fasting triglycerides ≤ 2.5 x ULN
- Fasting glucose < 1.5 x ULN
- Availability of FFPE tissue of GEP-NET or lung NET tumour tissue or patient willing to have a new biopsy in case of non-availability of tissue
Who cannot join
- Patients with only non-measurable lesions by CT
- Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin) or other contra-indications for everolimus ± SSA treatment
- Unavailable archival tissue and patient unwilling to have a new biopsy
- Prior treatment with everolimus
- History of drug hypersensitivity with a similar chemical structure to lanreotide Autogel 120mg, sandostatin LAR or everolimus
- Unresolved Grade 3 or 4 toxicity from prior therapy, including experimental therapy
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- History or clinical evidence of other malignancy within 3 years prior to enrolment, with the exception of adequately treated in-situ carcinoma of the cervix, uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer
- Major surgery within 4 weeks of first dose administration
- History of symptomatic brain metastases or other central nervous system metastases.
- Patients receiving concomitant immunosuppressive agents or chronic corticosteroid use at the time of study entry except in cases outlined below:
- Topical applications (e.g. rash) Inhaled sprays (e.g. obstructive airways disease)
- Eye drops
- Local injections (e.g. intra-articular)
- Stable low dose of corticosteroids for at least two weeks before enrolment
- Patients with known HIV seropositivity. Screening for HIV infection at baseline is not required
- Acute and chronic, active infectious disorders (including hepatitis patients)
- Chronic pulmonary medical conditions or acute respiratory problems
- Active bleeding diathesis
- On oral anti-vitamin K medication with an INR ≥3
- Any severe uncontrolled medical condition such as:
- Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤ 6 months prior to enrolment, uncontrolled cardiac arrhythmia
- Uncontrolled diabetes defined as fasting glycemia > 150 mg/dl.
- Acute and chronic, active infectious disorders and non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy.
- Symptomatic deterioration of lung function
- Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A (Rifabutin, Rifampicin, Clarithromycin, Ketoconazole, Itraconazoleonazole, Voriconazole, Ritonavir, Telithromycin) within the last 5 days prior to enrolment
- Patients that will likely require treatment during the study with drugs that are not permitted by the study protocol.
- History of non-compliance to medical regimens
- Concurrent anti-cancer treatment in another investigational trial, other than the everolimus ± SSA treatment
- Patients that are likely to require any additional concomitant treatment with anti-proliferative effect for the pancreatic neuroendocrine tumour
- Patients unwilling or unable to comply with the protocol or patients with mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude
- Any abnormal findings at baseline, clinical finding, including psychiatric and behavioural problems, or any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardize the patient's safety or decrease the chance of obtaining satisfactory data needed to achieve the objective(s) of the study
- Childbearing potential (unless using an adequate measure of contraception)
- Pregnancy or lactation. Females of childbearing potential must provide a negative pregnancy test at the start of study and must be using oral, double barrier or injectable contraception. Non-childbearing potential is defined as post-menopausal for at least 1 year, surgical sterilization or hysterectomy at least three months before the start of the study.
- Has previously been enrolled in this study
Trial locations and contacts
3 sites in 2 countries.
Marc Peeters contact
3 sites in 2 countries
Belgium2 sites, 2 recruiting
- Recruiting
Antwerp University Hospital
Edegem, Antwerp, 2650
Timon Vandamme
- Recruiting
VITAZ
Sint-Niklaas, East-Flanders, 9100
Willem Lybaert
About this study
Official title: A Prospective, Multicentric, Proof-of-concept Study to Evaluate the Value of Circulating Tumour DNA in Follow-up of Patients With an Advanced Gastroenteropancreatic or Lung Neuroendocrine Tumour Under Everolimus +- SSA Treatment
Prospective, multicentric, single arm, POC study to evaluate the value of CtDNA in follow-up of patients treated with everolimus, with or without somatostatin analogues for advanced gastroenteropancreatic or lung neuroendocrine tumours.
Read the detailed description
Prospective, multicentric, single arm, POC study to evaluate the value of CtDNA in follow-up of patients treated with everolimus, with or without somatostatin analogues for advanced gastroenteropancreatic or lung neuroendocrine tumours. Inclusion is possible after proven progressive disease on CT and/or DOTANOC scan (at physician's discretion) and decision of physician to start everolimus ± SSA treatment. During the study, CT and/or DOTANOC scans (thorax/abdomen/pelvis) (at physician's discretion) will be performed to detect progressive disease and CtDNA levels will be measured from the start of the treatment. The changes in CtDNA levels will be correlated to the tumour disease progression based on imaging (RECIST 1.1 and or PERCIST 1.0 (if available)) and laboratory and clinical markers. Characterization of CtDNA will be based on detection of tumour-specific alterations (i.e. mutations, copy number alterations and DNA methylation) using next-generation sequencing, digital droplet PCR and a photoelectrochemical biosensor. The identification of tumour-specific mutations will be done using next-generation sequencing of tumour tissue.
- Conditions
- Neuroendocrine Tumors
- Being tested
- Liquid biopsies, Scans (CT, gallium-68 DOTATE/TOC/NOC PET-CT)
- Keywords
- Liquid biopsies
- Medical subject headings
- Neuroendocrine Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liquid biopsiesOther
Blood/urine sampling and scans are done at regular intervals
Scans (CT, gallium-68 DOTATE/TOC/NOC PET-CT)Other
Scans will be done at regular intervals
| Study group | Role | What they receive |
|---|---|---|
| GEP-NET and lung-NET patients | Experimental | Liquid biopsies and scans Receives: Other: Liquid biopsies; Other: Scans (CT, gallium-68 DOTATE/TOC/NOC PET-CT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of treatment follow-up through CtDNA level measurement
Feasibility of treatment follow-up through detection of a change in CtDNA levels before progression is apparent on imaging according to RECIST 1.1 and/or PERCIST 1.0 (if available) (Progression-free survival (PFS)).
Measured: 48 months
Secondary outcomes (4)
PFS under everolimus ± SSA treatment
PFS under everolimus ± SSA treatment
Measured: 48 months
Overall response rates under everolimus ± SSA treatment
Overall response rates under everolimus ± SSA treatment
Measured: 48 months
Safety of everolimus ± SSA treatment according to the Common Terminology Criteria for Adverse Events 4 (CTCAE4) and in Belgium according to the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Number of patients with (serious) adverse events throughout the study
Measured: 48 months
Comparison of PFS based on RECIST 1.1 and PERCIST 1.0
Comparison of PFS based on RECIST 1.1 and PERCIST 1.0
Measured: 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2022
- Study start27 May 2019
- Primary completion27 May 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuroendocrine TumorsStudies of the same condition, open and under way.
- More trials run by University Hospital, AntwerpThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Antwerp
- Sponsor type
- University, hospital or other
- Collaborators
- Universiteit Antwerpen
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05268952
- Sponsor's protocol ID
- Liquid-NET 2.0
- Status last verified
- Jan 2022
- First submitted
- 21 Jan 2022
- Last updated
- 7 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Multicentric, Proof-of-concept Study to Evaluate the Value of Circulating Tumour DNA in Follow-up of Patients With an Advanced Gastroenteropancreatic or Lung Neuroendocrine Tumour Under Everolimus +- SSA Treatment
- ClinicalTrials.gov ID
- NCT05268952
- Acronym / sponsor ID
- Liquid-NET 2.0
- Conditions
- Neuroendocrine Tumors
- Keywords
- Liquid biopsies
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University Hospital, AntwerpUniversity, hospital or other
- Collaborators
- Universiteit Antwerpen
- Study start
- 27 May 2019 (actual)
- Primary completion
- 27 May 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 7 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Prospective, multicentric, single arm, POC study to evaluate the value of CtDNA in follow-up of patients treated with everolimus, with or without somatostatin analogues for advanced gastroenteropancreatic or lung neuroendocrine tumours.
Detailed description
Prospective, multicentric, single arm, POC study to evaluate the value of CtDNA in follow-up of patients treated with everolimus, with or without somatostatin analogues for advanced gastroenteropancreatic or lung neuroendocrine tumours. Inclusion is possible after proven progressive disease on CT and/or DOTANOC scan (at physician's discretion) and decision of physician to start everolimus ± SSA treatment. During the study, CT and/or DOTANOC scans (thorax/abdomen/pelvis) (at physician's discretion) will be performed to detect progressive disease and CtDNA levels will be measured from the start of the treatment. The changes in CtDNA levels will be correlated to the tumour disease progression based on imaging (RECIST 1.1 and or PERCIST 1.0 (if available)) and laboratory and clinical markers. Characterization of CtDNA will be based on detection of tumour-specific alterations (i.e. mutations, copy number alterations and DNA methylation) using next-generation sequencing, digital droplet PCR and a photoelectrochemical biosensor. The identification of tumour-specific mutations will be done using next-generation sequencing of tumour tissue.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GEP-NET and lung-NET patients | Experimental | Other: Liquid biopsies, Other: Scans (CT, gallium-68 DOTATE/TOC/NOC PET-CT)Liquid biopsies and scans |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Age ≥18 years
- Written informed consent prior to any study-related procedure
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Histological proven diagnosis of a well or moderately differentiated GEP-NET (WHO2017 grade 1,2,3 neuroendocrine tumour)
- Documented progressive gastroenteropancreatic or lung neuroendocrine tumour by means of imaging and based upon the RECIST 1.1 criteria and/or PERCIST 1.0 criteria (if available) for which the treating physician has decided to treat with everolimus ± SSA treatment
Key exclusion criteria (34 listed)
- Patients with only non-measurable lesions by CT
- Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin) or other contra-indications for everolimus ± SSA treatment
- Unavailable archival tissue and patient unwilling to have a new biopsy
- Prior treatment with everolimus
- History of drug hypersensitivity with a similar chemical structure to lanreotide Autogel 120mg, sandostatin LAR or everolimus
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Liquid biopsiesBlood/urine sampling and scans are done at regular intervals | Other | GEP-NET and lung-NET patients |
| Scans (CT, gallium-68 DOTATE/TOC/NOC PET-CT)Scans will be done at regular intervals | Other | GEP-NET and lung-NET patients |
Primary outcome
Feasibility of treatment follow-up through CtDNA level measurement
Time frame: 48 months
Feasibility of treatment follow-up through detection of a change in CtDNA levels before progression is apparent on imaging according to RECIST 1.1 and/or PERCIST 1.0 (if available) (Progression-free survival (PFS)).
4 secondary outcomes
PFS under everolimus ± SSA treatment
Time frame: 48 months
Overall response rates under everolimus ± SSA treatment
Time frame: 48 months
Safety of everolimus ± SSA treatment according to the Common Terminology Criteria for Adverse Events 4 (CTCAE4) and in Belgium according to the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Time frame: 48 months
Comparison of PFS based on RECIST 1.1 and PERCIST 1.0
Time frame: 48 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc Peeters contact
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Liquid biopsies and Scans (CT, gallium-68 DOTATE/TOC/NOC PET-CT) in people with Neuroendocrine Tumors, run by University Hospital, Antwerp at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Belgium, Cyprus. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Timon Vandamme (038212111, timon.vandamme@uza.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility of treatment follow-up through CtDNA level measurement (time frame: 48 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2022.