A Multi-Center, Open-Label Study of Surufatinib (HMPL-012) in Patients With Advanced Solid Tumors

Tumors Clinical Trial

Official title:

A Multi-Center, Open-Label, Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of Surufatinib (HMPL-012), Previously Named Sulfatinib in Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02549937
• Other study ID #: 2015-012-00US1
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: November 2015
• Est. completion date: June 2, 2023

Study information

• Verified date: February 2024
• Source: Hutchmed
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objective Dose Escalation:

To evaluate the safety and tolerability of surufatinib in patients with advanced solid tumors and to determine the maximum tolerable dose (MTD) or recommended phase II dose (RP2D).

Primary Objective Dose Expansion:

To evaluate the anticancer activity of surufatinib in patients with advanced Biliary Tract Cancer (BTC), patients with advanced pancreatic neuroendocrine tumors (pNETs), patients with locally advanced, unresectable, metastatic extra-pancreatic neuroendocrine tumors (EP-NETs), and patients with soft tissue sarcomas (STS) treated at a dose of 300 mg QD.

Secondary Objective:

To evaluate the pharmacokinetic profile of multiple dose surufatinib in patients with advanced solid tumors and to evaluate the anti cancer activity of surufatinib in patients with advanced solid tumors.

Description:

The study is an open-label, dose escalation and expansion clinical trial of surufatinib orally once daily (QD) in patients with advanced solid tumors.

The study consists of two phases:

Dose escalation phase - A 3+3 design will be used for this portion of the study.

• Approximately 15 to 35 evaluable patients will be enrolled. The actual number of patients depends on the Dose-limiting toxicity (DLT) situation as well as the RP2D dose level reached in this trial.

• The trial will approximately evaluate five surufatinib dose levels at 50,100, 200, 300 and 400 mg/day.

Expansion phase:

Approximately 105 patients will be enrolled into one of four open-label treatment arms during this phase: at least 30 patients with advanced BTC that has progressed on standard first-line chemotherapy will be assigned to Arm A, at least 15 patients with advanced pNET that has progressed on either everolimus, sunitinib, or both will be assigned to Arm B, at least 15 patients with advanced EP-NET that has progressed on everolimus will be assigned to Arm C, and at least 45 patients with Soft Tissue Sarcoma will be assigned to Arm D. Subjects enrolled in this phase are to be evaluated for the safety, tolerability and pharmacokinetic (PK) characteristics to confirm the selected surufatinib dose.

Subjects will receive surufatinib daily treatment continuously with every 28-day treatment cycle until disease progression, death, or intolerable toxicity at the investigator's discretion for a favorable benefit to risk balance.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 130
• Est. completion date: June 2, 2023
• Est. primary completion date: April 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Fully understand the study and voluntarily sign the informed consent form;

• At least 18 years old;

• Histologically or cytologically documented, locally advanced or metastatic solid malignancy of any type during the dose escalation phase, that has progressed on available standard systemic therapy, and for whom no effective therapy or standard of care exists; and locally advanced or metastatic BTC that has progressed on standard ?rst-line chemotherapy; locally advanced or metastatic pNET that has progressed on everolimus, sunitinib or both; locally advanced or metastatic EP-NET that has progressed on everolimus; advanced STS that has progressed on at least one line of standard therapy or refused standard frontline cytotoxic chemotherapy during the expansion phase;

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

• Hypertension that is not controlled by antihypertension medication, defined as:

systolic blood pressure = 140 mmHg and/or diastolic blood pressure = 90 mmHg;

• History or presence of digestive tract diseases, including active gastric/duodenal ulcer or ulcerative colitis, or active hemorrhage of an unresected gastrointestinal tumor, or an evaluation by investigators of having any other condition that could possibly result in gastrointestinal tract hemorrhage or perforation;

• History or presence of serious hemorrhage , hemoptysis or hematemesis within 3 months or a thromboembolic event (including Deep Vein Thrombosis (DVT), stroke and/or transient ischemic attack) within 6 months;

• Patients with squamous Non Small Cell Lung Cancer (NSCLC) should be excluded;

• Clinically significant cardiovascular disease, including but not limited to, acute myocardial infarction within 6 months prior to enrollment, severe/unstable angina pectoris or coronary artery bypass grafting, New York Heart Association Class III/IV congestive heart failure, ventricular arrhythmias requiring treatment or left ventricular ejection fraction (LVEF) < 50%;

• Systemic anti-neoplastic therapies within 4 weeks prior to the initiation of investigational treatment, including chemotherapy, radical radiotherapy, hormonotherapy, biotherapy and immunotherapy;

• Palliative radiotherapy for bone metastasis/lesion within 2 weeks;

• Known Human immunodeficiency virus (HIV) infection;

• Known clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis;

• Women who are pregnant or lactating;

• Brain metastases and/or spinal cord compression untreated with surgery and/or radiotherapy, and without clinical imaging evidence of stable disease for 14 days or longer; Subjects requiring steroids within 4 weeks prior to start of study treatment will be excluded;

• Inability to take medication orally, dysphagia or an active gastric ulcer resulting from previous surgery or a severe gastrointestinal disease, or any other condition that investigators believe may affect absorption of the investigational product;

• Received investigational treatment in another clinical study within 4 weeks prior to the initiation of investigational treatment;

• Other disease, metabolic disorder, physical examination anomaly, abnormal laboratory result, or any other condition that investigators suspect may prohibit use of the investigational product, affect interpretation of study results, or put the patient at high risk.

Related Conditions & MeSH terms

• Tumors

Intervention

Drug:
• surufatinib
orally once daily (QD) in patients with advanced solid tumor.

Locations

Country	Name	City	State
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
United States	Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Mary Crowley Cancer Research Center	Dallas	Texas
United States	Rocky Mountain Cancer Center	Denver	Colorado
United States	SCRI at HealthONE	Denver	Colorado
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	MD Anderson Cancer Center	Houston	Texas
United States	City of Hope Comprehensive Cancer Center	Los Angeles	California
United States	Tennessee Oncology	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mount Sinai Hospital	New York	New York
United States	Florida Cancer Specialists	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Hutchison Medipharma Limited

Countries where clinical trial is conducted

United States,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of DLT	The primary outcome during dose escalation will be the incidence rate of DLTs	From date of enrollment through end of Cycle 1, up to 28 days
Primary	Progression Free Survival (PFS) rate	The primary outcome during dose expansion will be the PFS rate for each cohort	From date of enrollment to progression or death up to 18 months
Secondary	maximum plasma concentration calculated with Blood samples	Blood samples will be taken to measure the levels of study drug.	within 30 days after the first dose
Secondary	time to reach maximum concentration calculated with Blood samples	Blood samples will be taken to measure the levels of study drug	within 30 days after the first dose
Secondary	Objective response rate	the proportion of subjects who have a Complete Response or Partial Response	within 30 days after the last dose