Cancer Patients With Solid Tumors Clinical Trial
Official title:
Evaluation of the Safety, Pharmacokinetics and Efficacy of Four Doses of YN968D1 in Subjects With Solid Tumors
| Verified date | September 2017 |
| Source | LSK BioPartners Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This protocol will be divided into two parts: Part 1 will evaluate the safety and pharmacokinetics of three doses of YN968D1 after a single administration followed by a 28-Day continuous course of therapy; Part 2 will evaluate the safety and preliminary efficacy in an open-label administration of YN968D1 at the MTD or a maximum of 750 mg. All subjects in Part 1 and Part 2 of this study will be permitted to continue therapy with only safety monitoring and bimonthly assessments for progression, if the product is well tolerated and the subject has stable disease or better. Up to 72 subjects will be enrolled in this clinical trial.
| Status | Completed |
| Enrollment | 55 |
| Est. completion date | May 2015 |
| Est. primary completion date | February 2015 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: 1. 18 years of age or older 2. Subjects may be enrolled with the following malignancies: - Part 1: Subjects with any solid malignant tumor that are refractory to conventional therapy or the subject does not tolerate the conventional therapy - Part 2: Subjects diagnosed with NSCLC, CRC, RCC, Gastric cancer, GIST or triple negative Breast Cancer that are refractory to conventional therapy or the subject does not tolerate the conventional therapy 3. Evaluable disease defined by RECIST 1.1 as measured by a suitable imaging technique 4. Life expectancy = 3 months 5. Subject must be suitable for oral administration of study medication 6. Signed written informed consent 7. Adequate bone marrow, renal, and liver function as manifested by the following: - CBC: ANC = 1500/mm3, platelets = 100,000/mm3, hemoglobin = 9.0 g/dL - CMP: Creatinine clearance > 50 mL/min or serum creatinine < 1.5 x ULN, serum bilirubin < 2.5 x ULN, AST and ALT = 5.0 × ULN - Coagulation profile with PT and INR, each = 1.5 x ULN - Proteinuria < 200 mg by 24- hour urine collection without evidence of active sediment or hematuria 8. ECOG performance status = 2 9. Female subjects of child-bearing potential must agree to use contraceptive measures starting 1 week before the administration of the first dose of YN968D1 until 4 weeks after discontinuing study drug and male subjects must agree to use contraceptive measures during the study and ending 4 weeks after last dose of study drug 10. Female patients of child-bearing potential are confirmed to have either a negative serum ß-hCG test, or have been evaluated by a gynecologist to confirm the patient is not pregnant, within 7 days prior to administration of initial dose of YN968D1 11. Ability and willingness to comply with the study protocol for the duration of the study and with follow-up procedures Exclusion Criteria: 1. Pregnant or lactating women 2. Therapy with clinically significant systemic anticoagulant or antithrombotic agents within 7 days prior to first scheduled dose of YN968D1 that may prevent clotting and in the opinion of the investigator would place the subject at risk. 3. Hemoptysis within 3 months prior to first scheduled dose of YN968D1 4. Cytotoxic chemotherapy, immunotherapy, or radiotherapy within 4 weeks (6 weeks in cases of mitomycin C, nitrosourea, lomustine) prior to first scheduled dose of YN968D1 5. Surgery or visceral (e.g., hepatic or renal) biopsy within 28 days prior to first scheduled dose of YN968D1 6. Minor surgical procedure performed within 7 days prior to first scheduled dose of YN968D1 7. Prior exposure to YN968D1 (prior treatment with an angiogenesis inhibitor is not exclusionary) 8. Concomitant treatment with strong inhibitors or inducers of CYP3A4, CYP2C9 and CYP2C19. 9. Known history of human immunodeficiency virus infection (HIV) 10. Subjects with active bacterial infections and/or receiving systemic antibiotics 11. Current or past diagnosis of leukemia within the past 5 years 12. Prior radiotherapy at the target lesion 13. Known CNS metastases or clinical evidence of CNS involvement that is not stable for last 3 months by radiology documentation 14. Medical history of non-healing wound within past 2 weeks 15. History of bleeding diathesis or bleeding within 14 days prior to enrollment 16. Medical history of clinically significant thrombosis (bleeding or clotting disorder) within the past 3-months that in the opinion of the investigator may place the patient at risk of side effects on an anti-angiogenesis product 17. History of non-malignant GI bleeding, gastric stress ulcerations, or peptic ulcer disease within the past 3-months that in the opinion of the investigator may place the patient at risk of side effects on an anti-angiogenesis product 18. History of idiopathic or hereditary angioedema 19. History of sickle cell or any hemolytic anemia 20. History of uncontrolled hypertension that in the opinion of the investigator is not well managed by medication and may place the patient at risk when taking a VEGF inhibitor 21. Complete left bundle branch block (LBBB), bifascicular block (RBBB with either left anterior hemiblock or left posterior hemiblock) 22. Any clinically significant ST segment and/or T-wave abnormalities 23. Presence of unstable atrial fibrillation (ventricular response rate > 100 bpm). Patients with stable atrial fibrillation are allowed in the study provided they do not meet another exclusion criteria 24. Myocardial infarction or unstable angina pectoris within 6 months prior to starting study medication 25. Congestive heart failure (New York Heart Association class III-IV) 26. History of other significant cardiovascular disease or vesicular disease within the last 6 months (e.g. such as hypertensive crisis, hypertensive encephalopathy, stroke or TIA, or significant peripheral vascular disease) that in the opinion of the investigator may place the patient at risk when taking a VEGF inhibitor 27. History of significant gastrointestinal disorders that in the opinion of the investigator may place the patient at risk when taking a VEGF inhibitor; such as an abdominal fistula, GI perforation, or bleeding ulcer within 2 months of treatment 28. QTcF >450 msec on screening ECG 29. Baseline echocardiogram (within 2 months) with left ventricular ejection fraction (LVEF) <50% 30. History of clinically significant glomerulonephritis, biopsy proven tubulointerstitial nephritis, crystal nephropathy, or other renal insufficiencies 31. History of myocardial infarction within the past 6 months 32. Treatment with an investigational agent within the longest time frame of either 5 half-lives or 30 days of initiating study drug 33. Medical or psychiatric illness that, in the opinion of the Investigator, may impact the safety of the subject or objectives of the study 34. Known recreational substance use or psychiatric illness that, in the opinion of the Investigator, may affect compliance with scheduled visits 35. Known hypersensitivity to YN968D1 or components of the formulation |
| Country | Name | City | State |
|---|---|---|---|
| Korea, Republic of | ASAN Medical Center | Seoul | |
| United States | Huntsman Cancer Institute | Salt Lake City | Utah |
| Lead Sponsor | Collaborator |
|---|---|
| LSK BioPartners Inc. | Bukwang Pharmaceutical, Co., Ltd. |
United States, Korea, Republic of,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Safety in the first 28-Days of Therapy | The primary endpoint is evaluation of safety during the first 28-day cycle of therapy following the initiation of multiple dosing of YN968D1. The safety variables to be evaluated in this study are adverse events, physical examinations, vital signs (specifically including blood pressure), clinical laboratory evaluations including serum chemistry, hematology (including RBC morphology and reticulocyte count), and urinalysis (with detailed sediment analysis, proteinuria, and 24-hour urine for collection for creatinine clearance and protein), and electrocardiograms (ECGs) in triplicate. | 28-Days after Discontinuation of YN968D1 | |
| Secondary | Pharmacokinetic Assessments for AUC, Cmax and Tmax | In Part 1 of this study, full PK profiles of YN968D1 will be obtained following administration of a single oral dose of YN968D1 on Day 1, and at steady state on Day 35±2. In Part 2 of this study, PK sampling will include a pre-dose and at the 4±1 hour time point on the first day of dosing in the first 28-Day cycle of therapy, and pre-dose on days 2, 7, 14 and 28 of the first 28-Day cycle of therapy | Day 1 Single Dose and Day 28 Steady State | |
| Secondary | Tumor Biomarkers for Specific Tumor Types | The primary Pharmacodynamic endpoints will include specific serum tumor markers for the target cancer, levels of endothelial growth factor (VEGF), and detection of EC-derived molecules such as sVEGFR-1, sVEGFR-2, sVEGFR-3, sTie-2 and VCAM-1, as well as PIGF. These biomarkers will be measured at baseline and at the end of every two 28-Day cycles of therapy. For patients that continue on repeat 28-Day cycles after the primary evaluation period, biomarkerts will be assessed after each two 28-Day cycles of therapy. | Every 28-Days | |
| Secondary | Objective Response Rate (RESIST) | Anti-tumoral efficacy will be assessed by best radiographic response based on Response Evaluation Criteria in Solid Tumors (RECIST v 1.1) at baseline (Day -14 to -1) and at the end of two 28-Day cycles of therapy (Part 1 - Day 35±2; or Part 2 56±2 Days). For patients that continue on repeat 28-Day cycles after the primary evaluation period, progression will be assessed after each two 28-Day cycles of therapy. | Every 56-Days |