Dose-Escalation and Safety Trial of YN968D1

NCT01497704 | Completed Phase 1

• 1 other identifier: BK-LSK-AM101
• Study Type: interventional
• Target: 55
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Cancer Patients With Solid Tumors

Keywords

Cancer; Tumor; Oncology; Antiangiogenesis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Pharmacokinetic Assessments for AUC, Cmax and Tmax

  Day 1 Single Dose and Day 28 Steady State

• Tumor Biomarkers for Specific Tumor Types

  Every 28-Days

• Objective Response Rate (RESIST)

  Every 56-Days

Study Arms (1)

YN968D1

EXPERIMENTAL

Active therapy arm for safety evaluation

Drug: YN968D1

Interventions

YN968D1 DRUG

Daily dosing of YN968D1 for treatment of solid tumors

Also known as: Apatinib

YN968D1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older
• 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
• Evaluable disease defined by RECIST 1.1 as measured by a suitable imaging technique
• Life expectancy ≥ 3 months
• Subject must be suitable for oral administration of study medication
• Signed written informed consent
• 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
• ECOG performance status ≤ 2
• 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

You may not qualify if:

• Pregnant or lactating women
• 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.
• Hemoptysis within 3 months prior to first scheduled dose of YN968D1
• Cytotoxic chemotherapy, immunotherapy, or radiotherapy within 4 weeks (6 weeks in cases of mitomycin C, nitrosourea, lomustine) prior to first scheduled dose of YN968D1
• Surgery or visceral (e.g., hepatic or renal) biopsy within 28 days prior to first scheduled dose of YN968D1
• Minor surgical procedure performed within 7 days prior to first scheduled dose of YN968D1
• Concomitant treatment with strong inhibitors or inducers of CYP3A4, CYP2C9 and CYP2C19.
• Known history of human immunodeficiency virus infection (HIV)
• Subjects with active bacterial infections and/or receiving systemic antibiotics
• Current or past diagnosis of leukemia within the past 5 years
• Prior radiotherapy at the target lesion
• Known CNS metastases or clinical evidence of CNS involvement that is not stable for last 3 months by radiology documentation
• Medical history of non-healing wound within past 2 weeks
• History of bleeding diathesis or bleeding within 14 days prior to enrollment
• 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

Sponsors & Collaborators

• Elevar Therapeutics: lead
• Bukwang Pharmaceutical, Co., Ltd.: collaborator

Study Sites (2)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

ASAN Medical Center

Seoul, 138-736, South Korea

Location

Related Publications (1)

• Kang YK, Ryu MH, Hong YS, Choi CM, Kim TW, Ryoo BY, Kim JE, Weis JR, Kingsford R, Park CH, Jang S, McGinn A, Werner TL, Sharma S. Phase 1/2a Study of Rivoceranib, a Selective VEGFR-2 Angiogenesis Inhibitor, in Patients with Advanced Solid Tumors. Cancer Res Treat. 2024 Jul;56(3):743-750. doi: 10.4143/crt.2023.980. Epub 2024 Jan 18.

  PMID: 38271925 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

apatinib

Study Officials

• Sunil Sharma, MD, FACP

  Huntsman Cancer Institute

  PRINCIPAL INVESTIGATOR

• Yoon-Koo Kang, MD, PhD

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2011
• First Posted: December 22, 2011
• Study Start: April 1, 2012
• Primary Completion: February 1, 2015
• Study Completion: May 1, 2015
• Last Updated: October 2, 2017

Record last verified: 2017-09

Locations

KR (1); US (1)