Open-Label Surufatinib in European Patients With NET

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Neuroendocrine Tumours; Neuroendocrine Tumour of the Lung; Small Intestinal NET
• Intervention / Treatment: Drug: Surufatinib

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 2

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

• Study Contact: Name: Nick Lawn; Phone Number: +44 7826 422448; Email: nickl@hutch-med.com

Study Locations

• France
  • Pessac, France, 33604
    • CHU Bordeaux
  • Villejuif, France, 94800
    • Institut Gustave Roussy
• Germany
  • Berlin, Germany, 13353
    • Charité Universitätsmedizin Berlin
  • Erlangen, Germany, 91054
    • Universitaetsklinikum Erlangen
  • Essen, Germany, 45147
    • Universitatsklinikum Essen, Klinik fur Endokrinologie
• Italy
  • Bari, Italy, 70124
    • Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari
  • Brescia, Italy, 25123
    • ASST-Spedali Civili di Brescia
  • Firenze, Italy, 50134
    • Universita degli Studi di Firenze - Azienda Ospedaliero Universitaria Careggi (AOUC)
  • Milano, Italy, 20141
    • Istituto Europeo Di Oncologia
• Norway
  • Bergen, Norway, 5021
    • Haukeland University Hospital
  • Oslo, Norway, 0372
    • Oslo University Hospital Rikshospitalet
• Spain
  • Barcelona, Spain, 8035
    • Hospital Vall Hebron
  • Barcelona, Spain, 8013
    • Institut Catala d'Oncologis (ICO) - Hospital Duran i Reynals
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon Y Cajal
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen Del Rocio
• United Kingdom
  • London, United Kingdom, W1G 6AD
    • Sarah Cannon Research Institute
  • Manchester, United Kingdom, M20 4BX
    • Christie Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama, Birmingham (UAB)
  • California
    • Orange, California, United States, 92868
      • University of California Irvine Medical Center UCIMC - H.H. Chao Comprehensive Digestive Disease Center CDDC
  • Georgia
    • Atlanta, Georgia, United States, 30322-1013
      • Emory University, Winship Cancer Institute
  • New York
    • Stony Brook, New York, United States, 11794
      • Stony Brook Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. 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;
2. Has radiologic evidence of progressive tumour within 12 months of study enrolment
3. Is willing and able to provide informed consent
4. Is ≥18 years of age
5. Has measurable lesions according to RECIST Version 1.1
6. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
7. 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:

1. 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
2. Major surgery within previous 4 weeks or radiation therapy within 2 weeks prior to the start of treatment.
3. Prior VEGF/VEGFR-targeted therapy
4. Uncontrollable hypertension, defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, despite antihypertensive medication
5. Gastrointestinal disease or condition within 6 months prior to first dose
6. 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.
7. Clinically significant cardiovascular disease.
8. 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.
9. 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.
10. 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.
11. Has a clinically meaningful ongoing infection (eg, requiring intravenous treatment with anti-infective therapy)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Surufatinib; 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; Surufatinib 300 mg oral once daily; Other Names: HMPL-012, sulfatinib

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hutchmed
• Investigators: Study Director: John Kauh, MD, Hutchmed

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2021
• Primary Completion (Estimated): September 15, 2024
• Study Completion (Estimated): September 15, 2024

Study Registration Dates

• First Submitted: September 23, 2020
• First Submitted That Met QC Criteria: October 4, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 8, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: VEGF
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplasms; Lung Neoplasms; Neuroendocrine Tumors
• Other Study ID Numbers: 2020-012-00EU1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No