Activity and safety of Everolimus in combination with octreotide LAR and Metformin in patients with advanced pancreatic well-differentiated Neuroendocrine Tumors (pWDNETs): a Phase II, open, monocentric, prospective study.

Phase 1

• Conditions: advanced/ or not resectable well differnciated pancreatic neuroendocrin tumor; MedDRA version: 16.1Level: LLTClassification code 10067518Term: Pancreatic neuroendocrine tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 16.1Level: PTClassification code 10068909Term: Pancreatic neuroendocrine tumour metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-000888-41-IT
• Lead Sponsor: Fondazione IRCCS Istituto Nazionale dei tumori

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-03-10
• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 43

Inclusion Criteria

Signature of written informed consent (approved by the Institutional Ethics Committee Independent ) obtained after a careful study of screening procedures .
2 . Age >= 18 years old.
3 . Patients with histological evidence of pNET well-differentiated G1 -G2 .
4 . Configurable tumor disease (according to RECIST ) .
5 . Karnofsky Performance Status >= 60%.
6 . Life expectancy greater than 6 months.
7 . Is permitted to enroll patients who have not received any treatment for advanced disease or patients pretreated with surgery , chemotherapy or somatostatin analogues .
8 . Basal blood tests :
- Counts of neutrophils in absolute value > 1.5 x 109 / L.
- Platelet count > 100 x 109 / L.
- Hemoglobin > 9 g / dl .
- Total Bilirubin < 1.5 times the upper limit of normal .
- AST, ALT <2.5 times the upper limit of normal in patients without evidence of liver metastases.
- AST, ALT <2.5 times the upper limit of normal in patients with evidence of liver metastases.
- Alkaline phosphatase <2.5 times the upper limit of normal in patients with evidence of hepatic metastases
- Values ??of serum creatinine < 1.5 mg / dl. - CCr = 60 mL / min

9 . During the study of male and female patients must use adequate contraceptive methods .
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 34
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 9

Exclusion Criteria

1 . Patients with histological evidence of malignant insulinoma ( pNET )
2 . Surgeries performed within 28 days prior to the start of treatment.
3 . Evidence of metastasis at the level of the central nervous system or spinal cord compression . Patients should be subjected to a recent study MRI or CT scan at least 28 days from the date of randomization.
4 . Clinically significant cardiovascular disease , such as cardiovascular accidents occurred in less than 6 months, unstable angina , congestive heart failure grade greater than or equal to II ( according to the classification of the New York Heart Association NYHA ) series cardiac arrhythmias that require treatment.
5 . Important comorbidities , metabolic disorders , clinical examination or laboratory investigations , which contraindicate the use of drugs to study, or patients at high risk of complications from the treatment.
6 . Active or uncontrolled severe infections .
7 . Cirrhosis , acute hepatitis or chronic active hepatitis .
8 . Poor control of diabetes HbA1c > = 8.0 % .
9 . Diabetic patients who are treated with metformin are eligible if they have enabled the treatment with metformin for less than 6 months. Are excluded diabetic patients who make use of other hypoglycemic agents such as sulfonylureas, insulin , glinides as monotherapy or in combination with metformin.
10 . Using anti - IL6 or IGF1 .
11 . Uncontrolled high blood pressure , atrial fibrillation .
12 . History of immunosuppression included positive HIV test .
13 . No previous or concomitant oncological pathology , except: basal cell skin cancer, in situ , as long as every other cancer patient disease-free for at least 5 years.
14 . They excluded patients with a condition of metabolic acidosis , acute or chronic , including ketoacitosi .
15 . History of alcohol abuse , or habitual intake of alcohol (= 3 glasses of alcoholic drinks / day) sufficient to cause hepatotoxicity.
16 . Prolonged fasting .
17 . Severe states of dehydration.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate progression free survival;Secondary Objective: safety, overall survival, response rate;Primary end point(s): safety, overall survival, response rate;Timepoint(s) of evaluation of this end point: 12 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): to evaluate circulant biomarkers levels (IL 6, IGF1);Timepoint(s) of evaluation of this end point: 1 year