Open-label study of surufatinib in Japanese patients
- Conditions
- Part 1 - relapsed / refractory non-hematologic malignancies, Part 2 - locally advanced NET
- Registration Number
- JPRN-jRCT2031210310
- Lead Sponsor
- ITOIGAWA Suguru
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 37
1. Male or female patients of Japanese ethnicity, equal to or more than 20 years of age.
2. Histologically or cytologically documented disease as follows:
a. Part 1: unresectable, locally advanced or metastatic nonhematologic malignancy that is relapsed or refractory to or intolerant of established therapies known to provide clinical benefit
b. 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
i. For NETs originating from the thorax,
A. Grade 1 is defined as less than 2 mitoses/10 high-power field (HPF) and no necrosis.
B. Grade 2 is defined as 2 to 10 mitoses/10 HPF and /or foci of necrosis.
ii. For NETs of origins other than thorax,
A. Grade 1 is defined as less than 2 mitoses/10 HPF and /or less than 3 percent Ki-67 index.
B. Grade 2 is defined as 2 to 20 mitoses/10 HPF and/or 3 percent to 20 percent Ki-67 index
iii. If the mitotic ratio and Ki-67 index correspond to different grades, the higher grade is used to assign classification.
iv. Patients who have functioning NETs and have been on a stable dose of an SSA for a minimum of 2 months prior to the first dose of study treatment for control of their secretory symptoms will be eligible.
3. Must have radiologic evidence of progressive tumor within 12 months of study enrollment.
4. Willing and able to provide informed consent.
5. Have evaluable lesions according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
a. Part 1: measurable or non-measurable lesions
b. Part 2: measurable lesions
6. Absolute neutrophil count of equal to or greater than 1.5 x 10*9/L, platelet count of equal to or great than 100 x 10*9/L, and hemoglobin equal to or greater than 9 g/dL.
7. Serum total bilirubin less than 1.5 times the upper limit of normal (ULN).
8. Proteinuria less than 2+ by urinalysis, or 24-hour urine collection equal to or less than 1 g of protein, or spot urine protein:urine creatinine ratio equal to or less than 1.9.
9. Liver function test requirements:
a. Part 1: Have alanine aminotransferase (ALT), AST, or alkaline phosphatase (ALP) levels equal to or less than 3 times the ULN
b. Part 2:
i. Patients without known liver metastases must have ALT, AST, or ALP levels equal to or less than 3 times the ULN
ii. Patients with known liver metastases must have ALT, AST, or ALP levels equal to or less than 5 times the ULN
10. Serum creatinine less than 1.5 times ULN OR creatinine clearance equal to or less than 60 mL/min.
11. International normalized ratio (INR) equal to or less than 1.5 x ULN and activated partial thromboplastin time (aPTT) equal to or less than 1.5 x ULN.
12. Have an ECOG performance score of 0 or 1.
13. Female patients of childbearing potential and male patients with partners of childbearing potential agree to use a highly effective form(s) of contraception that results in a low failure rate (less than 1percent per year) when used consistently and correctly, starting during the screening period, continuing throughout the entire study period, and for 90 days after taking the last dose of study drug. Such methods include oral progestogen-only hormonal contraception (combined oestrogen/progestogen which is available in Japan should be avoided) or highly effective non-oral hormonal contraception associated with inhibition of ovulation together with a barrier method (eg, diaphragm, condom with spermicide), intrauterine device, i
1. Women who are pregnant and lactating, or possibly pregnant. Women who temporarily stop lactating will not be permitted and will remain excluded.
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. If ILD is suspected, patients should be evaluated with a chest X-ray, oxygen saturation by pulse oximetry (SpO2), etc., to evaluate for evidence of ILD. For Part 2, ILD/noninfectious pneumonitis induced by treatment with everolimus that has recovered prior to starting study drug is not exclusionary. Recovered is defined as the patient is asymptomatic with an absence of clinical or image findings of ILD.
3. Known active viral hepatitis. For patients with a history of hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection who are currently on treatment are eligible if they have an undetectable HCV viral load. Patients with an unknown history of viral hepatitis must be screened for HBV with hepatitis B surface antigen (HBsAg) and HBV DNA, if indicated, and for HCV with HCV antibody. Patients receiving antivirals at screening should have been treated for greater than 2 weeks before the first dose of study drug. Patients with a negative HCV antibody test at screening or positive HCV antibody test followed by a negative HCV RNA test at screening are eligible. The HCV RNA test will be performed only for patients testing positive for HCV antibody.
4. Adverse events due to previous antitumor therapy has not recovered to equal to or less than Common Terminology Criteria for Adverse Events (NCI CTCAE) grade 1, except alopecia and peripheral neurotoxicity with equal to or less than NCI CTCAE grade 2 caused by platinum chemotherapy.
5. Uncontrolled hypertension, defined as systolic blood pressure equal to or greater than 140 mmHg and/or diastolic blood pressure equal to or greater than 90 mmHg despite optimal medical management.
6. Gastrointestinal disease or condition that investigators suspect may affect drug absorption, including, but not limited to, active gastric and duodenal ulcers, ulcerative colitis and other digestive disease, gastrointestinal tumor with active bleeding, or other gastrointestinal conditions that may cause bleeding or perforation by Investigaor's discreation.
7. History or presence of a serious haemorrhage (greater than 30 mL within 3 months of enrollment), hemoptysis (greater than 5 mL blood within 4 weeks of enrollment).
8. 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, congestive heart failure according to the New York Heart Association classification equal to or greater than 2; ventricular arrhythmias which need drug treatment; left ventricular ejection fraction less than 50 percent.
9. Mean corrected QT interval by Fridericia (QTcF) equal to or greater than 480 ms.
10. 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 drug will be excluded.
11. High risk of bleeding at screening due to tumor invasion into major vessels, s
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method