Clinical trial NCT02749331: Study of Recombinant Adenovirus AdVince in Patients With Neuroendocrine Tumors; Safety and Efficacy
Official title: Study of Recombinant Adenovirus (AdVince) in Patients With Neuroendocrine Tumors; Safety and Efficacy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Neuroendocrine Tumors
Lead sponsor: Uppsala University
Sponsor class: OTHER
First posted: 2016-04-22
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: An open-labelled, uncontrolled, single-center Phase I/IIa clinical study to evaluate the safety of repeated infusions of AdVince into the hepatic artery in patients with metastatic neuroendocrine tumors (NETs), and if possible determination of maximum tolerated dose.

Detailed description: An open-labelled, uncontrolled, single-center Phase I/IIa clinical study to evaluate the safety of repeated infusions of AdVince into the hepatic artery in patients with metastatic neuroendocrine tumors (NETs), and if possible determination of maximum tolerated dose. Secondary objectives include to evaluate the anti-tumoral efficacy of AdVince infusions on metastatic neuroendocrine tumors, to determine the replication profile of AdVince and to determine the humoral (antibody) and cytokine-mediated immune response to AdVince. Minimum 12 and maximum 35 patients will be included, the number is based on the toxicity observed.

Eligibility criteria: Inclusion Criteria:

1. Subject´s written informed consent
2. Histologically and radiologically confirmed progressive neuroendocrine carcinoma of gastrointestinal, pancreatic or bronchial origin with multiple liver metastases. Progression in Clinical symptoms and tumor growth verified over the last 6 months on CT or MRI
3. Cancer that is not considered resectable for potential cure or tumor reduction
4. Patent portal vein and adequate liver perfusion
5. Liver dominant disease with involvement of \<60% of liver parenchyma
6. Karnofsky performance status of \>=70%
7. Life expectancy of \>=6 months
8. \>=18 years of age
9. Must use a reliable method of contraception if sexually active and of reproductive potential
10. Plasma creatinine \<105 ug/ml
11. Aspartate transaminase (AST), Alanine transaminase (ALT) and Alkaline Phosphatase (ALP) \<3.0-fold upper limit of normal
12. Total bilirubin \<2.0-fold upper limit of normal
13. Prothrombin time (PT)/International Normalized Ratio (INR) \<2.0 and Prothromboplastin time (PTT) within normal limits
14. Neutrophils \>1500/ml, hemoglobin \>100 g/L, platelets \>100 000/ml
15. Patients with functioning NET should have cover by somatostatin analog

Exclusion Criteria:

1. Known chronic liver dysfunction Before the development of metastatic cancer (e.g. cirrhosis, chronic hepatitis)
2. Active infection, including documented HIV and hepatitis C
3. Any viral syndrome diagnosed within the previous 2 weeks
4. Chemotherapy within the previous 4 weeks Before the first treatment
5. Radiotherapy to the target tumor site within the last 24 weeks from the baseline CT scan
6. Concomitant malignancy
7. Pregnant or lactating females
8. Prior participation in any research protocol that involved administration of adenovirus vectors
9. Treatment with any other investigational therapy within the last 4 weeks, organ transplantation prior to treatment, severe cardiovascular, metabolic or pulmonary disease
10. Continuing treatment with any other cancer therapy

Primary outcomes:
measure: Number of Adverse Events (AE) according to Common Terminology Criteria for Adverse Events (CTCAE) v 4.03
timeFrame: From screening visit and through study completion, an average time of 18 months.
Secondary outcomes:
measure: Change in tumor size
timeFrame: Measured within 4 weeks before first treatment and after 80 +/-14 days (evaluation visit 1)
measure: Change in tumor size
timeFrame: Measured within 4 weeks before first treatment and after 214 +/- 14 days (evaluation visit 2)
measure: Change in tumor metabolic activity
timeFrame: Baseline value within 24 hrs before first treatment and after 80 +/- 14 days(evaluation visit 1)
measure: Change in tumor metabolic activity
timeFrame: Baseline value within 24 hrs before first treatment and after 214 +/- 14 days (evaluation visit 2)
measure: Progression-free survival (PFS)
timeFrame: Twelve weeks after 80 days from first treatment (4 treatment cycles) or the corresponding time.
measure: Change in replication profile of AdVince
timeFrame: Before and 4hrs after each treatment cycle up to a time period of 214 days.
measure: Change in replication profile of AdVince
timeFrame: Before and 24hrs after each treatment up to a time period of 214 days.
measure: Change in replication profile of AdVince
timeFrame: Before and 72hrs after each treatment cycle up to a time period of 214 days.
measure: Change in the humoral immune response to AdVince
timeFrame: At baseline, after 8+2 days, after 50 +/- 7days, optional after 124 +/- 7days and 184 +/- 7 days.
measure: Change in the cytokine-mediated immune response
timeFrame: At baseline and at 4hrs following each treatment up to a time period of 214 days.
measure: Change in the cytokine-mediated immune response
timeFrame: At baseline and at 24hrs following each treatment up to a time period of 214 days.
measure: Change in the cytokine-mediated immune response
timeFrame: At baseline and at 72hrs following each treatment up to a time period of 214 days.
Other outcomes:
Locations:
city: Uppsala
country: Sweden
facility: Endocrine Oncology Clinic, Uppsala University Hospital
Study officials:
affiliation: Uppsala University Hospital
name: Joakim Crona, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: