Open-label Study of Surufatinib in Japanese Patients

An Open-Label Study of Surufatinib in Japanese Patients With Neuroendocrine Tumors

This is a phase 1/2, open-label, multi-centre study of surufatinib in patients with unresectable, locally advanced, or recurrent nonhematologic malignancies who do not respond or are intolerant to standard of care.

Study Overview

• Status: Active, not recruiting
• Conditions: Neuroendocrine Tumors; Non-hematologic Malignancy
• Intervention / Treatment: Drug: Surufatinib

Detailed Description

The purpose of this study is to evaluate the tolerability and efficacy of surufatinib in Japanese patients.

The study will be conducted in 2 parts:

• Part 1 - evaluation of tolerability and safety of surufatinib and confirmation of the recommended clinical dose in Japanese patients with nonhematologic malignancies
• Part 2 - evaluation of antitumor activity and confirmation of tolerability of surufatinib in Japanese patients with NETs

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): 36
• Phase: Phase 2; Phase 1

Expanded Access

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

Contacts and Locations

• Study Contact: Name: Jennifer Lees, PhD; Phone Number: +61 1800559724; Email: ausmedinfo@hutch-med.com
• Study Contact Backup: Name: Chris Tucci; Email: Christucci@hutch-med.com

Study Locations

• Japan
  • Fukuoka, Japan, 812-0054
    • Kyushu University Hospital
  • Fukuoka, Japan, 814-0001
    • Fukuoka Sanno Hospital
  • Kagawa, Japan, 761-0793
    • Kagawa University Hospital
  • Kashiwa-shi, Japan, 277-8577
    • National Cancer Centre Hospital East
  • Kyoto, Japan, 606-8507
    • Kyoto University Hospital
  • Mitaka, Japan, 181-8611
    • Kyorin University Hospital
  • Nagoya, Japan, 464-8681
    • Aichi Cancer Centre
  • Osaka, Japan, 553-0003
    • Kansia Electric Power Hospital
  • Sapporo, Japan, 060-8648
    • Hokkaido University Hospital
  • Sendai, Japan, 890-8574,
    • Tohoku University Hospital
  • Tokyo, Japan, 104-004
    • National Cancer Centre Hospital
  • Yokohama, Japan, 236-0004
    • Yokohama City University Hospital

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. Histologically or cytologically documented disease as follows:

   1. Part 1: unresectable, locally advanced or metastatic nonhematologic malignancy that is relapsed/refractory to or intolerant of established therapies known to provide clinical benefit
   2. Part 2: locally advanced or metastatic, low (grade 1) or intermediate (grade 2) grade NETs that have been previously treated with at least 1 line of systemic therapy
2. Has radiologic evidence of progressive tumour within 12 months of study enrolment
3. Is willing and able to provide informed consent
4. Is ≥20 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. Women who are pregnant and lactating, or possibly pregnant.
2. Has a history of interstitial lung disease (ILD)/noninfectious pneumonitis, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
3. Known active viral hepatits
4. 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
5. Uncontrollable hypertension, defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, despite antihypertensive medication
6. Gastrointestinal disease or condition within 6 months prior to first dose
7. Has a history or presence of a serious haemorrhage (>30 mL within 3 months) or haemoptysis (>5 mL blood within 4 weeks)
8. Clinically significant cardiovascular disease.
9. 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.
10. 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.
11. 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 prior to first dosing.

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; Oral surufatinib 300 mg once daily in treatment cycles of 28 days starting at Cycle 1 Day1	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
Part 1: Incidence of treatment-emergent adverse events (TEAEs) graded by the Investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0).	To evaluate surufatinib-related adverse events in patients with NETs	Up to 2 years
Part 2: Objective response rate. This will be assessed on the proportion of participants with partial response or complete response as determined by the Investigator based on RECIST v1.1	The primary outcome of part 2 will be objective response rate in patients with NETs when treated with surufatinib	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Observed plasma concentrations of surufatinib which will be assessed by the Cmax, tmax, AUC, Cmin and CL/F	Blood sampling will be taken to measure levels of the study drug	Up to 2 years
Progression Free Survival (PFS) which is defined as the time from randomization to the first occurrence of disease progression as determined by the investigator based on RECIST v1.1, or death from any cause, whichever occurs first	The duration between the enrollment date and the first disease progression (PD) or death (whichever comes first).	Up to 2 years
Duration of Response (DOR) which will be defined as the time from the first response to disease progression documented after treatment initiation or death, whichever occurs first. DOR will include CR, CR plus CRi, overall response (OR), and CR plus CRh.	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 2 years

Collaborators and Investigators

• Sponsor: Hutchison Medipharma Limited
• Investigators: Study Director: William Schelman, MD, Hutchmed

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2021
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: September 20, 2021
• First Submitted That Met QC Criteria: September 30, 2021
• First Posted (Actual): October 14, 2021

Study Record Updates

• Last Update Posted (Actual): 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

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors
• Other Study ID Numbers: 2020-012-00JP1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No