TumorsPhase 1/2NCT02549937
A Multi-Center, Open-Label Study of Surufatinib (HMPL-012) in Patients With Advanced Solid Tumors
A Phase 1/2 study testing surufatinib in people with Tumors, run by Hutchmed at 12 sites in 2 countries.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tumors
- What is being tested?
- surufatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 12 sitesin 2 countries
- Study dates
- Nov 2015to 2 Jun 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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;
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- 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.
Trial locations and contacts
12 sites in 2 countries.
12 sites in 2 countries
United States11 sites
Mary Crowley Cancer Research Center
Dallas, Texas, 75230
Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75246
Rocky Mountain Cancer Center
Denver, Colorado, 80218
SCRI at HealthONE
Denver, Colorado, 80218
Virginia Cancer Specialists, PC
Fairfax, Virginia, 22031
MD Anderson Cancer Center
Houston, Texas, 77030
City of Hope Comprehensive Cancer Center
Los Angeles, California, 91010
Tennessee Oncology
Nashville, Tennessee, 37203
Mount Sinai Hospital
New York, New York, 10029
Memorial Sloan Kettering Cancer Center
New York, New York, 10072
Florida Cancer Specialists
Sarasota, Florida, 34232
About this study
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
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).
Read more
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.
Read the 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 115 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.
- Conditions
- Tumors
- Being tested
- surufatinib
- Keywords
- biliary, pancreatic, neuroendocrine, carcinoid, PNET, EP-NET, extrapancreatic, sarcoma, soft tissue sarcoma, STS, BTC
- Medical subject headings
- Neoplasms, Carcinoid Tumor, Neuroectodermal Tumors, Primitive, Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
surufatinibDrug
Also called HMPL-012, sulfatinib
orally once daily (QD) in patients with advanced solid tumor.
| Study group | Role | What they receive |
|---|---|---|
| Escalation 50 mg | Experimental | Escalation cohort at 50 mg/day Receives: Drug: surufatinib |
| Escalation 100mg | Experimental | Escalation cohort at 100 mg/day Receives: Drug: surufatinib |
| Escalation 200 mg | Experimental | Escalation cohort at 200 mg/day Receives: Drug: surufatinib |
| Escalation 300 mg | Experimental | Escalation cohort at 300 mg/day Receives: Drug: surufatinib |
| Escalation 400 mg | Experimental | Escalation cohort at 400 mg/day Receives: Drug: surufatinib |
| Expansion | Experimental | 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. Receives: Drug: surufatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-Escalation Phase: Number of Patients With Dose-Limiting Toxicities (DLTs)
A DLT was defined as any of the following toxicities determined by the Investigator to have a reasonable possibility of being related to surufatinib. Adverse events (AE) were graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Any Grade 4 non-hematological toxicity; any Grade 3 non-hematological toxicity except for nausea/vomiting, diarrhea, constipation, electrolyte imbalances, or transient hypertension downgraded within 3 days with appropriate supportive treatment; Grade 4 neutropenia lasting >7 days; Grade 3 febrile neutropenia (absolute neutrophil count <1.0 × 10^9/liter (L) with a single temperature of >38.3 degree Celsius (°C) or a sustained temperature of >=38°C for more than 1 hour; Grade 4 thrombocytopenia or >=Grade 3 thrombocytopenia associated with tendency to bleed; dose interruption or delay for >14 days due to toxicity; any life-threatening complication or abnormality not covered in NCI CTCAE v. 4.03.
Measured: From the first dose of study drug (Day 1) up to Day 28 of Cycle 1
Dose-Escalation Phase: Number of Patients With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An AE was any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug or other protocol-imposed drug, regardless of attribution. An SAE was an AE that resulted in any of the following outcomes: was fatal; was life threatening; required or prolonged inpatient hospitalization; resulted in persistent or significant disability/incapacity; a congenital anomaly/birth defect in a neonate/infant born to a female patient or female partner of a male patient exposed to the study drug(s); was considered a significant medical event by the Investigator. TEAEs were defined as any AEs that started or worsened in severity on or after the first administration date of study drug and no later than 30 (+7) days after the last administration date of study drug or initiation of new anti-tumor therapy (whichever occurred first).
Measured: From the first dose of study drug (Day 1) up to approximately 90 months
Dose-Expansion Phase: Arms A and D: Progression Free Survival (PFS) Rate at 16 Weeks
The tumor response was determined according to the international Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 guideline. PFS is defined as the time (in months) from the start date of study medication (Day 1) until the date of objective disease progression as defined by RECIST Version 1.1 or death (by any cause in the absence of progression), whichever occurred earlier. PFS rate probability at 16 week was estimated. Progression is defined by RECIST v1.0 as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline or appearance of 1 or more new lesions.
Measured: At 16 weeks
Dose-Expansion Phase: Arms B and C: PFS Rate at 11 Months
The tumor response was determined according to the RECIST v1.1 guideline. PFS is defined as the time (in months) from the start date of study medication (Day 1) until the date of objective disease progression as defined by RECIST Version 1.1 or death (by any cause in the absence of progression), whichever occurred earlier. PFS rate probability at 11 months was estimated. Progression is defined by RECIST v1.0 as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline or appearance of 1 or more new lesions.
Measured: At 11 months
Secondary outcomes (10)
Dose-Escalation and Dose-Expansion Phase: Maximum Observed Plasma Concentration (Cmax) of Surufatinib
Plasma samples were collected to determine Cmax of surufatinib. The pharmacokinetic (PK) parameters were determined by non-compartmental analysis.
Measured: Pre-dose and 1, 2, 4, 6, 8 hours post-dose on Days 1 and 15 of Cycle 1
Dose Escalation and Dose-Expansion Phase: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Surufatinib
Plasma samples were collected to determine Tmax of surufatinib. The PK parameters were determined by non-compartmental analysis.
Measured: Pre-dose and 1, 2, 4, 6, and 8 hours post-dose on Days 1 and 15 of Cycle 1
Dose-Escalation and Dose-Expansion Phase: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24h) of Surufatinib
Plasma samples were collected to determine AUC0-24h of surufatinib. The PK parameters were determined by non-compartmental analysis. Data from pre-dose to 8 hours post-dose were extrapolated to obtain the AUC0-24 data.
Measured: Pre-dose and 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1
Dose-Escalation and Dose-Expansion Phase: AUC Over the Dosing Interval (AUCtau) of Surufatinib
Plasma samples were collected to determine AUCtau of surufatinib. The PK parameters were determined by non-compartmental analysis.
Measured: Pre-dose and 1, 2, 4, 6, and 8 hours post-dose on Day 15 of Cycle 1
Dose-Escalation and Dose-Expansion Phase: Objective Response Rate (ORR)
The ORR was defined as the percentage of patients achieving a complete response (CR) or partial response (PR) as confirmed best overall response (BOR) as determined by the Investigator using RECIST v1.1. The BOR was defined as the best response recorded from the start of study treatment until documented RECIST version 1.1 progression, death, or withdrawal of consent. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Measured: RECIST assessments performed at screening (within 28 days before start of study treatment), Day 1 of Cycle 2, and every 8 (+/-1 week) weeks afterwards until the occurrence of disease progression, up to a maximum of 90 months
Dose-Escalation and Dose-Expansion Phase: Disease Control Rate (DCR)
The DCR was defined as the percentage of patients who achieved a CR, PR or stable disease (SD) as confirmed BOR as determined by the Investigator using RECIST v1.1. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum on study.
Measured: RECIST assessments performed at screening (within 28 days before start of study treatment), Day 1 of Cycle 2, and every 8 (+/-1 week) weeks afterwards until the occurrence of disease progression, up to a maximum of 90 months
Dose-Escalation and Dose-Expansion Phase: Duration of Response (DoR)
The DoR was defined as the time from the first time that the objective response reached CR or PR, whichever came first (and later confirmed), until the occurrence of PD or death. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters. The appearance of 1 or more new lesions was also considered progression.
Measured: RECIST assessments performed at screening (within 28 days before start of study treatment), Day 1 of Cycle 2, and every 8 (+/-1 week) weeks afterwards until the occurrence of disease progression, up to a maximum of 90 months
Dose-Escalation Phase: Progression-Free Survival (PFS)
The PFS was defined as the time from the start date of study drug until the date of objective PD as assessed by the Investigator using RECIST version 1.1 or death (by any cause in the absence of progression).
Measured: RECIST assessments performed at screening (within 28 days before start of study treatment), Day 1 of Cycle 2, and every 8 (+/-1 week) weeks afterwards until the occurrence of disease progression, up to a maximum of 53 months
Dose-Expansion Phase: Time to Response (TTR)
The TTR was defined as the time from the start of study drug until first documented response (and later confirmed) according to RECIST v.1.1 for responders only.
Measured: RECIST assessments performed at screening (within 28 days before start of study treatment), Day 1 of Cycle 2, and every 8 (+/-1 week) weeks afterwards until the occurrence of disease progression, up to a maximum of 53 months
Dose-Escalation and Dose-Expansion Phase: Maximum Percentage Change From Baseline in Tumor Size as Per RECIST v1.1
Percentage change in tumor size was determined for patients with measurable disease at baseline and was derived at each visit by the percentage change in the sum of the diameters of target lesions compared to baseline, mean of maximum percentage change is presented. Baseline was defined as the last evaluable tumor assessment result obtained prior to the administration of study drug (including unscheduled assessments).
Measured: RECIST assessments performed at screening (within 28 days before start of study treatment), Day 1 of Cycle 2, and every 8 (+/-1 week) weeks afterwards until the occurrence of disease progression, up to a maximum of 90 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2015 (estimated)
- Study startNov 2015
- Primary completion25 Apr 2023
- Study completion2 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TumorsStudies of the same condition, open and under way.
- More trials run by HutchmedThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hutchmed
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Marjo Hahka-Kemppinen, MD, PhD, Study director, Hutchmed
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02549937
- Sponsor's protocol ID
- 2015-012-00US1
- Status last verified
- Jul 2024
- First submitted
- 13 Jul 2015
- Last updated
- 10 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
- Expanded access
- Available
Publications
Dasari A, Hamilton EP, Falchook GS, Wang JS, Li D, Sung MW, Chien C, Nanda S, Tucci C, Hahka-Kemppinen M, Paulson AS. A dose escalation/expansion study evaluating dose, safety, and efficacy of the novel tyrosine kinase inhibitor surufatinib, which inhibits VEGFR 1, 2, & 3, FGFR 1, and CSF1R, in US patients with neuroendocrine tumors. Invest New Drugs. 2023 Jun;41(3):421-430. doi: 10.1007/s10637-023-01359-2. Epub 2023 Apr 19.
PubMed 37074571
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02549937
- Acronym / sponsor ID
- 2015-012-00US1
- Conditions
- Tumors
- Keywords
- biliary, pancreatic, neuroendocrine, carcinoid, PNET, EP-NET, extrapancreatic, sarcoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 130 participants (actual)
- Lead sponsor
- HutchmedIndustry (pharma, biotech, devices)
- Study start
- Nov 2015 (actual)
- Primary completion
- 25 Apr 2023 (actual)
- Study completion
- 2 Jun 2023 (actual)
- First posted
- 15 Sep 2015 (estimated)
- Results
- Posted 10 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 115 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Escalation 50 mg | Experimental | Drug: surufatinibEscalation cohort at 50 mg/day |
| Escalation 100mg | Experimental | Drug: surufatinibEscalation cohort at 100 mg/day |
| Escalation 200 mg | Experimental | Drug: surufatinibEscalation cohort at 200 mg/day |
| Escalation 300 mg | Experimental | Drug: surufatinibEscalation cohort at 300 mg/day |
| Escalation 400 mg | Experimental | Drug: surufatinibEscalation cohort at 400 mg/day |
| Expansion | Experimental | Drug: surufatinibSubjects 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (14 listed)
- 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%;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| surufatinibAlso: HMPL-012, sulfatiniborally once daily (QD) in patients with advanced solid tumor. | Drug | Escalation 100mg, Escalation 200 mg, Escalation 300 mg, Escalation 400 mg, Escalation 50 mg, Expansion |
Primary outcome
Dose-Escalation Phase: Number of Patients With Dose-Limiting Toxicities (DLTs)
Time frame: From the first dose of study drug (Day 1) up to Day 28 of Cycle 1
A DLT was defined as any of the following toxicities determined by the Investigator to have a reasonable possibility of being related to surufatinib. Adverse events (AE) were graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Any Grade 4 non-hematological toxicity; any Grade 3 non-hematological toxicity except for nausea/vomiting, diarrhea, constipation, electrolyte imbalances, or transient hypertension downgraded within 3 days with appropriate supportive treatment; Grade 4 neutropenia lasting >7 days; Grade 3 febrile neutropenia (absolute neutrophil count <1.0 × 10^9/liter (L) with a single temperature of >38.3 degree Celsius (°C) or a sustained temperature of >=38°C for more than 1 hour; Grade 4 thrombocytopenia or >=Grade 3 thrombocytopenia associated with tendency to bleed; dose interruption or delay for >14 days due to toxicity; any life-threatening complication or abnormality not covered in NCI CTCAE v. 4.03.
Dose-Escalation Phase: Number of Patients With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Time frame: From the first dose of study drug (Day 1) up to approximately 90 months
An AE was any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug or other protocol-imposed drug, regardless of attribution. An SAE was an AE that resulted in any of the following outcomes: was fatal; was life threatening; required or prolonged inpatient hospitalization; resulted in persistent or significant disability/incapacity; a congenital anomaly/birth defect in a neonate/infant born to a female patient or female partner of a male patient exposed to the study drug(s); was considered a significant medical event by the Investigator. TEAEs were defined as any AEs that started or worsened in severity on or after the first administration date of study drug and no later than 30 (+7) days after the last administration date of study drug or initiation of new anti-tumor therapy (whichever occurred first).
Dose-Expansion Phase: Arms A and D: Progression Free Survival (PFS) Rate at 16 Weeks
Time frame: At 16 weeks
The tumor response was determined according to the international Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 guideline. PFS is defined as the time (in months) from the start date of study medication (Day 1) until the date of objective disease progression as defined by RECIST Version 1.1 or death (by any cause in the absence of progression), whichever occurred earlier. PFS rate probability at 16 week was estimated. Progression is defined by RECIST v1.0 as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline or appearance of 1 or more new lesions.
Dose-Expansion Phase: Arms B and C: PFS Rate at 11 Months
Time frame: At 11 months
The tumor response was determined according to the RECIST v1.1 guideline. PFS is defined as the time (in months) from the start date of study medication (Day 1) until the date of objective disease progression as defined by RECIST Version 1.1 or death (by any cause in the absence of progression), whichever occurred earlier. PFS rate probability at 11 months was estimated. Progression is defined by RECIST v1.0 as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline or appearance of 1 or more new lesions.
10 secondary outcomes
Dose-Escalation and Dose-Expansion Phase: Maximum Observed Plasma Concentration (Cmax) of Surufatinib
Time frame: Pre-dose and 1, 2, 4, 6, 8 hours post-dose on Days 1 and 15 of Cycle 1
Dose Escalation and Dose-Expansion Phase: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Surufatinib
Time frame: Pre-dose and 1, 2, 4, 6, and 8 hours post-dose on Days 1 and 15 of Cycle 1
Dose-Escalation and Dose-Expansion Phase: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24h) of Surufatinib
Time frame: Pre-dose and 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1
Dose-Escalation and Dose-Expansion Phase: AUC Over the Dosing Interval (AUCtau) of Surufatinib
Time frame: Pre-dose and 1, 2, 4, 6, and 8 hours post-dose on Day 15 of Cycle 1
Dose-Escalation and Dose-Expansion Phase: Objective Response Rate (ORR)
Time frame: RECIST assessments performed at screening (within 28 days before start of study treatment), Day 1 of Cycle 2, and every 8 (+/-1 week) weeks afterwards until the occurrence of disease progression, up to a maximum of 90 months
Dose-Escalation and Dose-Expansion Phase: Disease Control Rate (DCR)
Time frame: RECIST assessments performed at screening (within 28 days before start of study treatment), Day 1 of Cycle 2, and every 8 (+/-1 week) weeks afterwards until the occurrence of disease progression, up to a maximum of 90 months
Dose-Escalation and Dose-Expansion Phase: Duration of Response (DoR)
Time frame: RECIST assessments performed at screening (within 28 days before start of study treatment), Day 1 of Cycle 2, and every 8 (+/-1 week) weeks afterwards until the occurrence of disease progression, up to a maximum of 90 months
Dose-Escalation Phase: Progression-Free Survival (PFS)
Time frame: RECIST assessments performed at screening (within 28 days before start of study treatment), Day 1 of Cycle 2, and every 8 (+/-1 week) weeks afterwards until the occurrence of disease progression, up to a maximum of 53 months
Dose-Expansion Phase: Time to Response (TTR)
Time frame: RECIST assessments performed at screening (within 28 days before start of study treatment), Day 1 of Cycle 2, and every 8 (+/-1 week) weeks afterwards until the occurrence of disease progression, up to a maximum of 53 months
Dose-Escalation and Dose-Expansion Phase: Maximum Percentage Change From Baseline in Tumor Size as Per RECIST v1.1
Time frame: RECIST assessments performed at screening (within 28 days before start of study treatment), Day 1 of Cycle 2, and every 8 (+/-1 week) weeks afterwards until the occurrence of disease progression, up to a maximum of 90 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37074571Dasari A, Hamilton EP, Falchook GS, Wang JS, Li D, Sung MW, Chien C, Nanda S, Tucci C, Hahka-Kemppinen M, Paulson AS. A dose escalation/expansion study evaluating dose, safety, and efficacy of the novel tyrosine kinase inhibitor surufatinib, which inhibits VEGFR 1, 2, & 3, FGFR 1, and CSF1R, in US patients with neuroendocrine tumors. Invest New Drugs. 2023 Jun;41(3):421-430. doi: 10.1007/s10637-023-01359-2. Epub 2023 Apr 19.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marjo Hahka-Kemppinen, MD, PhD study director
Hutchmed
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing surufatinib in people with Tumors, run by Hutchmed at 12 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-Escalation Phase: Number of Patients With Dose-Limiting Toxicities (DLTs) (time frame: From the first dose of study drug (Day 1) up to Day 28 of Cycle 1). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02549937, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2024.