ETTLE Study NeuroEndocrine Tumour Therapy with Lutetium-177 octreotate and EverolimusNeuroendocrine tumour therapy for the treatment of advanced gastroenteropancreatic neuroendocrine tumours (GEP-NETs): the NETTLE Study

Phase 1

• Conditions: neuroendocrine tumour; Cancer - Neuroendocrine tumour (NET)

• Registration Number: ACTRN12611000207910
• Lead Sponsor: Fremantle Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-02-22
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: ot yet recruiting
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1Presence of advanced, unresectable GEP-NET, which have progressed on standard therapy, or those with uncontrolled symptoms, or massive disease requiring urgent treatment. Tumour has been biopsy - proven and avid on 68Ga-octreotate PET CT or on tracer 177Lu-octreotate or 111In-octreotide gamma scanning
2Age > 18 years
3WHO performance status < 2
4Neutrophils >1.5 x 109/L, platelets > 100 x 109/L, Hb > 90 g/L
5Bilirubin < 1.5 x ULN, ALT/AST < 2.5 x ULN ( < 5 x ULN in patients with liver metastases)
6Fasting serum cholesterol < 7.75 mmol/L AND triglycerides < 2.5 x ULN
7INR < 1.5 (Anticoagulation is allowed if target INR < 1.5 on a stable dose of warfarin or on a stable dose of LMW heparin for > 2 weeks at time of enrolment
8Serum creatinine < 1.5 x ULN
9Signed informed consent
10Accessible for follow-up

Exclusion Criteria

1Patients who have received anti-cancer therapies within 4 weeks of start of study drug
(including chemotherapy, radiation, antibody based therapy, etc)
2Patients who had major surgery or significant traumatic injury within 4 weeks of start of study drug, or may require major surgery during the course of the study
3Prior treatment with an investigational drug within preceding 4 weeks
4Patients receiving chronic systemic corticosteroids or another immunosuppressive agent.
Topical or inhaled corticosteroids allowed.
5Patients should not receive immunization with attenuated live vaccines within 1 week of study entry or during study period and should not be in close contact with people who have received attenuated live vaccines. Live vaccines include intranasal influenza, MMR, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines.
6Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.
7Other malignancies within the past 3 years except for neuroendocrine tumour or adequately treated cancer of the cervix or basal/squamous cell carcinomata of the skin.
8Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation such as: NYHA Class 111 or IV, unstable angina, symptomatic congestive cardiac failure, myocardial infarction within 6 months of start of study, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease.
9Severely impaired lung function defined by spirometry and DLCO that is 50% of normal predicted value and/or O2 sat that is < 88% at rest on room air
10Uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN
11Active liver infections or disease such as cirrhosis, or severe hepatic impairment (Child-Pugh class C)
12HBV, HCV or HIV positive
13Impairment of gastrointestinal function or GI disease that may significantly alter the absorption of everolimus (e.g ulcerative disease, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome or substantial small bowel resection)
14Patients with an active bleeding diathesis
15Female patients who are pregnant/breastfeeding
16Adults of reproductive potential and their partners who are not using effective birth control methods.
Adequate contraception must be used throughout the trial and for 8 weeks after the last dose of study drug, by both sexes.
17Women of childbearing potential must have negative urine/serum pregnancy test within 7 days prior to administration of everolimus)
18Patients who received prior treatment with an mTOR inhibitor (e.g sirolimus, temsirolimus,everolimus)
19Patients with a know hypersensitivity to everolimus or other rapamycins (e.g sirolimus, temsirolimus) or to its excipients
20History of non- compliance to medical regimens
21Patients unwilling, or unable to comply with the protocol
22Previous radiopeptide therapy within the last 6 months.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Progression-free survival measurement of target lesions on computer tomography, usings standard Response Evaluation in Solid Tumours (RECIST) criteria version 1.1 2009[Objective response rate evaluation at 1 year from commencement of treatment];Overal survival as determined by direct individual patient folllow-up by the Investigators[Actuarial survival 1,2,3 years from commencement of treatment]

Secondary Outcome Measures

Name	Time	Method
Toxicity is assesed according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3 (CTCAE)[3 year from commencement of treatment. Myelotoxicity fortnightly for 8 months. Nephrotoxicity 6 monthly for 3 years]