Neuroendocrine Tumours MedDRA version: 21.0 Level: PT Classification code 10052399 Term: Neuroendocrine tumour System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Fexofenadine
Product Code: [NA]
Pharmaceutical Form: Coated tablet
INN or Proposed INN: FEXOFENADINA CLORIDRATO
CAS Number: 83799-24-0
Current Sponsor code: Fexofenadine
Concentration un
Sponsors
Hutchison MediPharma Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has histologically or cytologically documented, locally advanced, or metastatic NET and has progressed on at least 1 prior line of therapy, but no more than 3 therapies: a. Cohort A: NET of lung origin b. Cohort B: NET of small bowel origin c. Cohort C: NET of non-small bowel, non-pancreas, and non-lung origin d. Cohort D (DDI substudy): NET of any origin 2. Has radiologic evidence of progressive tumour within 12 months of study enrolment 3. Is willing and able to provide informed consent 4. Is =18 years of age 5. Has measurable lesions according to RECIST Version 1.1 6. Has absolute neutrophil count of = 1.5×109/L, platelet count of = 100×109/L, and haemoglobin = 9 g/dL 7. Has serum total bilirubin 1.5 or activated partial thromboplastin time (aPTT) >1.5×ULN 12. Has an Eastern Cooperative Oncology Group (ECOG) performance status 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 (=65 years) yes F.1.3.1 Number of subjects for this age range 38
Exclusion criteria
Exclusion criteria: 1. 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 2. Major surgery within previous 4 weeks or radiation therapy within 2 weeks prior to the start of treatment. Prior palliative radiotherapy for metastatic lesions is permitted if there is at least one measurable lesion that has not been irradiated. 3. Prior VEGF/VEGFR-targeted therapy 4. Has uncontrollable hypertension, defined as systolic blood pressure =140 mmHg and/or diastolic blood pressure =90 mmHg, despite antihypertensive medication 5. PT/INR >1.5 or activated partial thromboplastin time (aPTT) >1.5×ULN. For patients on Coumadin or coumadin-like products, please refer to Section 7.3.3) 6. Has gastrointestinal disease or condition within 6 months prior to first dose that investigators suspect may affect drug absorption, including, but not limited to, active gastric and duodenal ulcers, ulcerative colitis and other digestive disease, gastrointestinal tumour with active bleeding, or other gastrointestinal conditions that could, in the investigators judgment, result in bleeding or perforation 7. Has a history or presence of a serious haemorrhage (>30 mL within 3 months) or haemoptysis (>5 mL blood within 4 weeks) within 6 months of first dose of study drug 8. Has clinically significant cardiovascular disease, including, but not limited to, acute myocardial infarction within 6 months prior to enrolment, severe/unstable angina pectoris or coronary artery bypass grafting, congestive heart failure =2 according to the New York Heart Association classification, ventricular arrhythmia that needs drug treatment, and left ventricular ejection fraction (LVEF) <50% 9. Has a mean corrected QT interval by Fridericia (QTcF) =480 ms 10. Has 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 11. Has 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 12. 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 6 months prior to first dose of study drug 13. Use of strong inducers or inhibitors of CYP3A4 within 2 weeks before the first dose of surufatinib 14. For Cohort D, use of medications that are known substrates, inhibitors, or inducers of CYP3A or substrates of P-gp or BCRP within 3 weeks before the first dose of the drug cocktail 15. Prior history of other cancer except those treated with curative intent for in situ non-melanoma skin cancer, breast, or cervical cancer, or those treated with curative intent and no evidence of disease in the last 5 years prior to enrolment in the study 16. Has a clinically meaningful ongoing infection 17. Has clinical symptoms consistent with pancreatitis 18. Has a history of allergies to any ingredient of surufatinib or its capsule shell, including tartrazine (E 102)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the anti-tumour activity of surufatinib in patients with low-to intermediate-grade (Grade 1 or Grade 2), well differentiated NET;Secondary Objective: - To characterise the PK of surufatinib in patients with NET - To evaluate the effect of surufatinib on cardiac repolarisation, as detected by changes in ECG QTc, and the potential relationship with surufatinib plasma concentrations - To further characterise the antitumour activity of surufatinib in patients with NET - Cohort D only: To evaluate the effects of repeat dosing of surufatinib on the single-dose PK of CYP3A4, P-gp, and BCRP) substrates in patients with NET - To evaluate the safety and tolerability of surufatinib in patients with NET;Primary end point(s): Disease Control Rate (DCR);Timepoint(s) of evaluation of this end point: 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Observed plasma concentrations, estimated population PK, and exposure parameters of surufatinib - QTc and plasma concentrations of surufatinib at specified time points - Additional efficacy endpoints • Objective Response Rate (ORR) • Time to Response (TTR) • Duration of Response (DoR) • Progressive-Free Survival (PFS) - Cohort D only: Exposure parameters of CYP3A4, P-gp, and BCRP substrates - Safety assessments include: • Frequency and severity of AEs • Physical examination findings • Vital signs • Laboratory tests • ECG • Echocardiograms/MUGA;Timepoint(s) of evaluation of this end point: PK Plasma Sampling: Day (-1 & -2) & at specific timepoints as per Schedule of Events (SOE) ECG for QTc Evaluation: At pre & post-dose on Cycle 1 Day 1 and Cycle 1 Day 15 (+1 week) at specific time points given in SOE ORR: Time to attain best overall response or CR or PR per RECIST Version 1.1 TTR: Time between the start date of study drug until first documented response (CR or PR) according to RECIST Version 1.1 DoR: Timepoint at which the objective response reaches CR or PR, whichever comes first, until the occurrence of PD or death PFS: Time from the start of study drug to date of objective disease progression as defined by RECIST Version 1.1 or death, whichever comes first. Echocardiogram/MUGA: At screening, Every 12 weeks (±7 days) after the first dose AEs, SAEs: Screening, EOT | — |
Countries
France, Germany, Italy, Norway, Spain, United Kingdom
Contacts
Public ContactNick Lawn
Hutchison MediPharma Limited
Outcome results
None listed