Clinical trial NCT05077384: Open-label Study of Surufatinib in Japanese Patients
Official title: An Open-Label Study of Surufatinib in Japanese Patients With Neuroendocrine Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Neuroendocrine Tumors
Non-hematologic Malignancy
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
First posted: 2021-10-14
Enrollment: 36
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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).
timeFrame: Up to 2 years
measure: 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
timeFrame: Up to 2 years
Secondary outcomes:
measure: Observed plasma concentrations of surufatinib which will be assessed by the Cmax, tmax, AUC, Cmin and CL/F
timeFrame: Up to 2 years
measure: 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
timeFrame: Up to 2 years
measure: 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.
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Fukuoka
country: Japan
facility: Fukuoka Sanno Hospital
city: Kagawa
country: Japan
facility: Kagawa University Hospital
city: Kashiwa-shi
country: Japan
facility: National Cancer Centre Hospital East
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Mitaka
country: Japan
facility: Kyorin University Hospital
city: Nagoya
country: Japan
facility: Aichi Cancer Centre
city: Osaka
country: Japan
facility: Kansia Electric Power Hospital
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
city: Sendai
country: Japan
facility: Tohoku University Hospital
city: Tokyo
country: Japan
facility: National Cancer Centre Hospital
city: Yokohama
country: Japan
facility: Yokohama City University Hospital
Study officials:
affiliation: Hutchmed
name: William Schelman, MD
role: STUDY_DIRECTOR
References: