Open-Label Surufatinib in European Patients With NET

Study Overview
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Brief Summary
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This is a Phase 2, open-label, multi-centre study of surufatinib in patients with low to intermediate grade (Grade 1 or Grade 2), well-differentiated neuroendocrine tumours (NETs).

Detailed Description
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This is a Phase 2, open-label, multi-centre study of surufatinib in patients with low- to intermediate-grade (Grade 1 or Grade 2), well-differentiated NETs. The study will enroll 4 cohorts of varying NETs, as follows: Cohort A - NET of lung origin Cohort B - NET of small bowel origin Cohort C - NET of non-small bowel, non-pancreas, and non-lung origin Cohort D - NET of any origin (DDI substudy) All patients will be treated with oral surufatinib 300 mg QD in treatment cycles of 28 days starting on Cycle 1 Day 1.

Official Title
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An Open-Label Phase 2 Study of Surufatinib in Patients With Neuroendocrine Tumours in Europe

Conditions
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Neuroendocrine Tumours, Neuroendocrine Tumour of the Lung, Small Intestinal NET

Intervention / Treatment
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* Drug: Surufatinib


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Has histologically or cytologically documented, locally advanced, or metastatic NET and has progressed on at least 1 prior line of therapy, but no more than 3 therapies; Has radiologic evidence of progressive tumour within 12 months of study enrolment Is willing and able to provide informed consent Is ≥18 years of age Has measurable lesions according to RECIST Version 1.1 Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Female patients of childbearing potential and male patients with partners of childbearing potential agree to use a highly effective form(s) of contraception Key Exclusion Criteria: Has an AE due to previous anti-tumour therapy that has not recovered to ≤CTCAE Grade 1, except alopecia and peripheral neurotoxicity with ≤CTCAE Grade 2 caused by platinum chemotherapy Major surgery within previous 4 weeks or radiation therapy within 2 weeks prior to the start of treatment. Prior VEGF/VEGFR-targeted therapy Uncontrollable hypertension, defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, despite antihypertensive medication Gastrointestinal disease or condition within 6 months prior to first dose Has a history or presence of a serious haemorrhage (>30 mL within 3 months) or haemoptysis (>5 mL blood within 4 weeks) within 6 months of first dose of study drug. Clinically significant cardiovascular disease. Brain metastases and/or spinal cord compression untreated with surgery and/or radiotherapy, and without clinical imaging evidence of stable disease (SD) for 14 days or longer; patients requiring steroids within 4 weeks prior to start of study treatment will be excluded. A high risk of bleeding at screening due to tumour invasion into major vessels, such as pulmonary artery, the superior vena cava, or the inferior vena cava, as determined by investigators. Has arterial thrombosis or deep venous thrombosis within 6 months prior to first dosing, or thromboembolic events (including stroke and/or transient ischaemic attack) within 12 months. Has a clinically meaningful ongoing infection (eg, requiring intravenous treatment with anti-infective therapy)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Surufatinib<br>Cohorts A, B, and C: oral surufatinib 300 mg once daily in treatment cycles of 28 days starting at Cycle 1 Day1 Cohort D: Surufatinib 300 mg once daily in treatment cycles of 28 days starting at Cycle 1 Day and single doses of drug cocktail on Day-2 and Day 15 Cycle 1 | Drug: Surufatinib<br>* Surufatinib 300 mg oral once daily<br>* Other names: HMPL-012, sulfatinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate (DCR) | Disease control rate the incidence of complete response, partial response and stable disease. | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentrations of surufatinib with blood sampling | Blood sampling will be taken to measure levels of the study drug in all cohorts and cytochrome P450 in cohort D only | up to 12 months | 
| QTc change from Baseline | QTc change from baseline in approximately first 40 patients (Cohorts A, B, and C) | up to 6 months | 
| Evaluation of safety and tolerability of surufatinib | Evaluate the safety and tolerability of surufatinib in patients with NET | Up to 12 months | 
| Progression Free Survival (PFS) | the duration between the enrollment date and the first disease progression (PD) or death (whichever comes first). | up to 12 months | 
| Duration of Response (DOR) | The duration between the date the criteria for complete response or partial response was first measured (first record shall prevail) and the date of disease recurrence or progression as objectively recorded | up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VEGF