Evaluating circulating tumor DNA in patients with advanced neuroendocrine tumors receiving treatment

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

This study is testing if measuring circulating tumor DNA can help track how well treatment is working for people with advanced neuroendocrine tumors.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Hospital, Antwerp (Academic / other)
• Locations: 3 sites (Edegem, Antwerp and 2 other locations)
• Trial ID: NCT05268952 on ClinicalTrials.gov

What this trial studies

This study aims to assess the value of circulating tumor DNA (CtDNA) in monitoring patients with advanced gastroenteropancreatic or lung neuroendocrine tumors who are being treated with everolimus, with or without somatostatin analogues. It is a prospective, multicentric, single-arm study where patients will undergo imaging scans and have their CtDNA levels measured to correlate with disease progression. The study will utilize advanced techniques such as next-generation sequencing and digital droplet PCR to identify tumor-specific alterations. The goal is to determine how changes in CtDNA levels relate to tumor progression as assessed by imaging and clinical markers.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a confirmed diagnosis of advanced gastroenteropancreatic or lung neuroendocrine tumors who have shown disease progression.

Not a fit: Patients who have previously been treated with everolimus or those with poorly differentiated neuroendocrine tumors may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a non-invasive method for monitoring treatment response and disease progression in patients with neuroendocrine tumors.

How similar studies have performed: Other studies utilizing liquid biopsies for monitoring cancer treatment have shown promising results, indicating potential success for this approach.

Eligibility criteria

Inclusion Criteria:

* 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
* Adequate bone marrow and coagulation function as shown by:

  1. Haemoglobin ≥ 9.0 g/dL
  2. ANC ≥ 1,500/mm3 (≥1.5 x 109/L)
  3. Platelets ≥ 100,000/mm3 (≥ 100x 109/L)
  4. INR ≤ 2.0
* Adequate liver function as shown by:

  1. Alanine aminotransferase and aspartate aminotransferase ≤2.5xULN (Upper limit of normal) (or ≤ 5 if hepatic metastases are present)
  2. 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

  1. Fasting serum cholesterol ≤ 300 mg/dL or 7.75 mmol/L
  2. Fasting triglycerides ≤ 2.5 x ULN
  3. 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

Exclusion Criteria:

* 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
* 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:

  1. Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤ 6 months prior to enrolment, uncontrolled cardiac arrhythmia
  2. Uncontrolled diabetes defined as fasting glycemia \> 150 mg/dl.
  3. 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.
  4. 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

Where this trial is running

Edegem, Antwerp and 2 other locations

• Antwerp University Hospital — Edegem, Antwerp, Belgium (Recruiting)
• Vitaz — Sint-Niklaas, East-Flanders, Belgium (Recruiting)
• Bank of Cyprus Oncology Center — Nicosia, Cyprus (Terminated)

Study contacts

• Study coordinator: Timon Vandamme

Conditions Neuroendocrine Tumors; Liquid biopsies