None listed
Conditions
Brief summary
The aim of this study is to estimate the treatment effect of Everolimus in patients with pancreatic neuroendocrine tumours (PNET). Who is it for? You may be eligible to join this study if you are aged over 18 years and have newly diagnosed locally advanced or metastatic confirmed pancreatic neuroendocrine tumour (NET) of intermediate grade. Trial details All participants will receive treatment with Everolimus. This is a drug that can block activity of a protein called mTOR, and can slow the growth of different tumours including pancreatic NETs in the laboratory. Large studies in patients with pancreatic NET have shown that Everolimus treatment decreased the rate of tumour growth and increased patient survival. Two tablets of 5 mg Everolimus will be given daily for 6 months. Participants will be assessed regularly throughout the treatment period, and every 3 months after treatment has stopped in order to determine treatment effect. CT and PET scans will be used to measure tumour response and questionnaires will also be supplied to patients to assess symptomatic response to treatment.
Interventions
Active Name - Everolimus
Trade Name - Afinitor
Patients will take 2 tablets of 5 mg (10mg) of everolimus orally, once daily for 6 months. A treatment cycle is defined as 28 days.
Sponsors
Peter MacCallum Cancer Centre
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1) Newly diagnosed locally advanced or metastatic histologically confirmed pancreatic NET of intermediate grade (Ki67 of 3-20%), not suitable for radical or aggressive resection or hepatic-directed approaches (including ablation, TACE or SIRT therapy) 2) Functional imaging criteria: (i)Disease must be FDG-avid and (ii)Disease may or may not express somatostatin-receptor (SSTR) on In-111 octreotide SPECT/CT or Ga-68 octreotate PET/CT 3)Measurable/evaluable disease per RECIST Version 1.1,1 determined by relevant imaging based on disease site (i.e. by multiphase MRI or triphasic CT scan for hepatic metastasis) 4) ECOG PS 0-2 5) Age > 18 years 6)Adequate organ function i)Bone marrow: Platelets > 100x10^9/L, Neutrophils > 1.5x10^9/L ii) Liver: Bilirubin less than or equal to 2.5 xUNL, INR less than or equal to 1.3, AST/ALT less than or equal to 2.5 xUNL (if no hepatic metastases) or AST/ALT less than or equal to 5.0 xUNL (if hepatic metastases). iii) Serum lipase and amylase less than and equal to 2 x ULN iv) Renal: Creatinine clearance (CrCl) greater than and equal to 40mL/min (assessed by modified Cockroft-Gault or nuclear renal scan)
Exclusion criteria
1) Poorly differentiated pancreatic NET with Ki67 > 20% 2) Well differentiated pancreatic NET with Ki67 less than and equal to 2%, unless FDG-avid (in which case confirmatory re-biopsy with estimation of Ki67 is required. If on re-biopsy the ki67 is greater than 20% the patient will be excluded) 3) Patients requiring ongoing SSA for symptomatic control or control of hormone secretory syndromes 4) Patients who have received prior therapy with mTOR inhibitors (e.g. sirolimus, temsirolimus) 5) Patients who have received any cytotoxic chemotherapy, targeted therapy, or biotherapy for pNETs 6) Patients with a known hypersensitivity to everolimus or other rapamycin analogs (sirolimus, temsirolimus) or to their excipients. 7) Prior treatment with radiolabelled SSAs within the last 12 months. 8) Patients with hepatic artery embolization, cryoablation or radiofrequency ablation of hepatic metastasis within the last 3 months prior to registration. 9) Patients who have received radiotherapy of target lesions, unless documented progression at that site. 10) Patients who have received local radiotherapy of non-target lesions for local symptom control within the last 2 weeks must have recovered from any adverse effects of radiotherapy prior to therapy. 11) Patients who have undergone major surgery/surgical therapy for any cause within 1 month. 12) Patients who have not recovered from any previous treatment for any cause and who have not reached ECOG performance status 0-2 before entering the study. 13) Patients receiving chronic treatment with corticosteroids or another immunosuppressive agent. 14) Patients who are not biochemically euthyroid. Patients with a history of hypothyroidism are eligible if they are on adequate and stable replacement thyroid hormone therapy and have been for at least 3 months. 15) Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: i) Uncontrolled diabetes as defined by HbA1c greater than and equal to 8% despite adequate therapy, ii) Fasting serum cholesterol > 7.75 mmol/L or fasting triglycerides > 2.5 ULN despite appropriate lipid lowering medication. iii) Severely impaired lung function defined as spirometry and DLCO that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air. DLCO should be adjusted to haemoglobin value and patient lung volumes. iv) Patients with the presence of active or suspected acute or chronic uncontrolled infection or with a history of immunodeficiency, including a positive HIV test result (ELISA and Western blot) v) Non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with this study treatment. vi) Liver disease such as cirrhosis, decompensated liver disease, chronic active hepatitis or chronic persistent hepatitis, except carriers of or chronic hepatitis B and C. 16) Patients who have a history of another primary malignancy within the last 3 years, with the exception of locally excised non-melanoma skin cancer and carcinoma in situ of uterine cervix 17) Symptomatic CNS metastases requiring corticosteroid therapy. 18) Patients who have any current or prior medical condition that may interfere with the conduct of the study or the evaluation of its results in the opinion of the Investigator or the Sponsor’s Medical Monitor. 19) Patients with a history of non-compliance to medical regimens or who are considered potentially not able to complete the entire study. 20) Patients who are currently part of, or have participated in, any clinical investigation with an investigational drug within 1 month prior to dosing. 21) Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum hCG laboratory test (> 5 mIU/mL). Patients with elevated hCG at baseline that is judged to be related to the tumour are eligible if hCG levels do not show the expected doubling when repeated 5-7 days later, or pregnancy has been ruled out by vaginal ultrasound. 22) Women of child-bearing potential, unless they are using adequate birth control methods. i) Adequate barrier methods of contraception include: diaphragm, intrauterine device (copper or hormonal), sponge or spermicide. Hormonal contraceptives include any marketed contraceptive agent that includes an estrogen and/or a progestational agent). ii) Reliable contraception should be maintained throughout the study and for 8 weeks after discontinuation of everolimus, whatever comes last.
Outcome results
None listed