Neuroendocrine neoplasms (NENs) is a heterogeneous group with varying symptoms, tumor biology and treatment response. NENs may occur in any organ, most commonly they are observed in the gastroenteropancreatic system and lungs. Most NEN patients are diagnosed at advanced stage, 65% of them will die within 5 years. The only curative treatment is surgery with complete resection of the primary tumor. However, more than 50% of patients exhibit metastatic disease, where there is no cure. MedDRA vers
Conditions
Interventions
Product Name: Ad5PTD(CgA-E1AmiR122)
Product Code: AdVince
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Ad5PTD(CgA-E1AmiR122)
Other descriptive name: AdVince
Concentration unit: mil
Sponsors
Department of Immunology, Genetics and Pathology (IGP), Rudbeck Laboratory, Uppsala University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject's written informed consent 2. Histologically confirmed NEN of gastrointestinal, pancreatic or bronchial origin 3. Disease progression verified over the last 6 months on CT or MRI using criteria employed in standard practice at the local hospital 4. Disease that is not considered resectable for potential cure or tumor reduction 5. Standard anti-cancer therapy exhausted according to the European Society of Medical Oncology (ESMO) guidelines for GEP-NETs and according to the European Neuroendocrine Tumor Society (ENETS) guidelines for lung carcinoids 6. Adequate liver perfusion ensured e.g. by patent portal vein, patent hepatic veins 7. Liver dominant disease with involvement of 1,500/µl, haemoglobin > 100 g/L, platelets > 100,000/µl 17. Patients with functioning NEN should have cover by somatostatin analog Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 17 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 18
Exclusion criteria
Exclusion criteria: 18. Known chronic liver dysfunction before the development of metastatic cancer (e.g., cirrhosis, chronic hepatitis) 19. Active infection, including documented HIV and hepatitis C 20. Any viral syndrome diagnosed within the previous 2 weeks 21. Systemic anti-cancer therapy (except for somatostatin analogues) within the previous 4 weeks before the first treatment 22. Radiotherapy to the target tumor site within the last 24 weeks from the baseline CT scan. 23. Evidence of clinically significant immunosuppression such as primary immunodeficiency state such as Severe Combined Immunodeficiency Disease 24. Requirement of treatment with corticosteroids (prednisone >10 mg/day or equivalent) 25. Concomitant malignancy 26. Pregnant or lactating females 27. Prior participation in any research protocol that involved administration of adenovirus vectors 28. Treatment with any other investigational therapy within the last 4 weeks, organ transplantation prior to treatment, severe cardiovascular, metabolic or pulmonary disease 29. Continuing treatment with any other cancer therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the safety of repeated infusions of AdVince into the hepatic artery in patients with metastatic NENs and if possible determination of maximum tolerated dose (MTD).;Secondary Objective: Secondary objectives include the following: (a) to evaluate the anti-tumoral efficacy of AdVince infusions on metastatic neuroendocrine tumors (b) to determine the replication profile of AdVince (c) to determine the humoral and cytokine-mediated immune responses to AdVince ;Primary end point(s): (a) Number of Adverse Events (AE) according to CTCA v 4.03, probably or possibly reated to the study drug or local injuries caused by the administration procedure (b) Identify Dose Limiting Toxicity (DLT), if possible (c) Changes in laboratory parameters and vital signs over time vs baseline values ;Timepoint(s) of evaluation of this end point: AE reported from the first study-related procedure until 30 days following the last dose. DLT from first until last injection of Advince Laboratory efficacy parameters: at baseline (before first treatment), before and after each injection. Biological serum markers before and 24, 48 and 72 h after each treatment. Laboratory safety parameters: - at baseline visit before cycle 1 - at treatment baseline: within 24 hrs before each treatment cycle 2-8 - after each treatment cycle 1-8 (24 h, 48 h and 72 h), - at Evaluation 1 visit - at Evaluation 2 visit - at check-up visits (approximately 8 days after each treatment) - at follow-up visits Local injuries: Checked at each administration of Advince. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): (a) Tumor size and tumor metabolic activity by: - Computer tomography (CT) and/or positron emission tomography (PET) and/or magnetic resonance imaging (MRI) before first and after last treatment cycle - Hormone level screening (biological markers) - Progression-free survival (PFS) 24 weeks after 4th cycle. (b) Viral replication by adenovirus quantification of in patients’ blood on day 1, 8, 22 and 50; before and 24h after injection, as well as 72h after injection by QRT-PCR. (c) Humoral response by detection of anti-adenovirus neutralizing antibodies at baseline, day 8 and day 50. Cytokine-mediated immune response is determined by cytokine measurement in plasma at baseline, 24h and 72h (optional) following virus injections.;Timepoint(s) of evaluation of this end point: -CR and/or PET and/or MRI before first cycle of treatment and after last cycle of treatment. -Hormone level screening at: Baseline (pretreatment). Day before treatment cycles 2-4, 5-8. 24h, 48h and 72h after each cycle. At evaluation 1 and 2. At check-ups day 30, day 58, approx. 8 days after cycles 5-8, follow-up 16 weeks after last treatment and every 12 weeks until progressive disease. -Progression-free survival 24 weeks after cycle 4. -Quantification of Adenovirus genome copies in blood at day 1, 8, 22 and 50, before and 24h, 72h after each injection. -Detection af anti-adenovirus antibodies at baseline, on day 8 and day 50. Cytokine measurement at baseline and 24h, 72h following injection of virus for cycles 1-4. | — |
Countries
Sweden
Contacts
Public ContactDept of IGP, Rudbeck laboratory
Uppsala University
Outcome results
None listed