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

Sponsor

Hutchison Medipharma Limited (Industry)

Overall Status

Recruiting

CT.gov ID

NCT02549937

Collaborator

(none)

152

Enrollment

Locations

Arms

Anticipated Duration (Months)

11.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Tumors	Drug: surufatinib	Phase 1/Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

152 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Nov 1, 2015

Anticipated Primary Completion Date :

Jun 7, 2022

Anticipated Study Completion Date :

Oct 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Escalation 50 mg Escalation cohort at 50 mg/day	Drug: surufatinib orally once daily (QD) in patients with advanced solid tumor. Other Names: HMPL-012 sulfatinib
Experimental: Escalation 100mg Escalation cohort at 100 mg/day	Drug: surufatinib orally once daily (QD) in patients with advanced solid tumor. Other Names: HMPL-012 sulfatinib
Experimental: Escalation 200 mg Escalation cohort at 200 mg/day	Drug: surufatinib orally once daily (QD) in patients with advanced solid tumor. Other Names: HMPL-012 sulfatinib
Experimental: Escalation 300 mg Escalation cohort at 300 mg/day	Drug: surufatinib orally once daily (QD) in patients with advanced solid tumor. Other Names: HMPL-012 sulfatinib
Experimental: Escalation 400 mg Escalation cohort at 400 mg/day	Drug: surufatinib orally once daily (QD) in patients with advanced solid tumor. Other Names: HMPL-012 sulfatinib
Experimental: Expansion Subjects will receive RP2D surufatinib daily treatment continuously with every 28-day treatment cycle. Four expansion cohorts will enroll BTC, pNET, EP-NET, and STS patients, respectively.	Drug: surufatinib orally once daily (QD) in patients with advanced solid tumor. Other Names: HMPL-012 sulfatinib

Outcome Measures

Primary Outcome Measures

Incidence of DLT [From date of enrollment through end of Cycle 1, up to 28 days]
The primary outcome during dose escalation will be the incidence rate of DLTs
Progression Free Survival (PFS) rate [From date of enrollment to progression or death up to 18 months]
The primary outcome during dose expansion will be the PFS rate for each cohort

Secondary Outcome Measures

maximum plasma concentration calculated with Blood samples [within 30 days after the first dose]
Blood samples will be taken to measure the levels of study drug.
time to reach maximum concentration calculated with Blood samples [within 30 days after the first dose]
Blood samples will be taken to measure the levels of study drug
Objective response rate [within 30 days after the last dose]
the proportion of subjects who have a Complete Response or Partial Response

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 ﬁrst-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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Comprehensive Cancer Center	Los Angeles	California	United States	91010
2	Rocky Mountain Cancer Center	Denver	Colorado	United States	80218
3	SCRI at HealthONE	Denver	Colorado	United States	80218
4	Florida Cancer Specialists	Sarasota	Florida	United States	34232
5	Mount Sinai Hospital	New York	New York	United States	10029
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10072
7	Tennessee Oncology	Nashville	Tennessee	United States	37203
8	Mary Crowley Cancer Research Center	Dallas	Texas	United States	75230
9	Baylor Charles A. Sammons Cancer Center	Dallas	Texas	United States	75246
10	MD Anderson Cancer Center	Houston	Texas	United States	77030
11	Virginia Cancer Specialists, PC	Fairfax	Virginia	United States	22031
12	Froedtert Hospital	Milwaukee	Wisconsin	United States	53226
13	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano		Italy