A Study of AL2846 on Tolerance and Pharmacokinetics

Phase I Study of Tolerance and Pharmacokinetics of AL2846 in Patients With Advanced Cancer

A study of AL2846,a C-met/Hepatocyte growth factor tyrosine kinase inhibitor,in patients with advanced cancer.

Study Overview

• Status: Unknown
• Conditions: Advanced Cancer
• Intervention / Treatment: Drug: AL2846

Detailed Description

To study the pharmacokinetic characteristics of AL2846 in the human body; To recommend a reasonable dose and indication for subsequent research.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yuankai Shi, doctor; Email: syuankaipumc@126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histological documentation of Advanced solid tumors（especially Hepatocellular Carcinoma and Lung Cancer ）,at least one measurable lesion (by RECIST1.1)
• Lack of the standard treatment or treatment failure
• 18-65 years,ECOG PS:0-1,Life expectancy of more than 3 months
• 30 Days or more from the last cytotoxic therapy
• Main organs function is normal
• Women of childbearing potential should agree to use and utilize an adequate method of contraception (such as intrauterine device，contraceptive and condom) throughout treatment and for at least 6 months after study is stopped；the result of serum or urine pregnancy test should be negative within 7 days prior to study enrollment，and the patients required to be non-lactating；Man participants should agree to use and utilize an adequate method of contraception throughout treatment and for at least 6 months after study is stopped
• Patients should participate in the study voluntarily and sign informed consent

Exclusion Criteria:

• Patients suffering from other malignancies currently or ever, except for cured cervical carcinoma in situ, non-melanoma skin cancers
• Patients with factors that could affect oral medication (such as dysphagia，chronic diarrhea, intestinal obstruction etc.)
• Patients participated in other anticancer drug clinical trials within 4 weeks or Patients participating in other clinical trials now
• Blood pressure unable to be controlled ideally by one drug(systolic pressure≥140 mmHg，diastolic pressure≥90 mmHg); Patients with Grade 1 or higher myocardial ischemia, myocardial infarction or malignant arrhythmias(including male QTc≥450ms,female QTc≥470ms) and patients with Grade 1 or higher congestive heart failure (NYHA Classification)
• Urine protein ≥ ++，and 24-hour urinary protein excretion>1.0 g confirmed
• Patients with non-healing wounds or fractures
• Patients with drug abuse history and unable to get rid of or Patients with mental disorders
• History of immunodeficiency
• Patients with concomitant diseases which could seriously endanger their own safety or could affect completion of the study according to investigators' judgment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AL2846; AL2846 QD po and it should be continued until disease progression or intolerable toxicity or patients withdrawal of consent	Drug: AL2846; AL2846 p.o. qd

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The type of dose-limiting toxicity(ies) (DLT[s]) of AL2846	Subjects within 28 days after treatment appear the following toxicity reaction relate to the drug ：II °or above of kidney damage，III °or above of non-hematological toxicity,IV°hematological toxicity ,Neutropenia associated with fever.	For 4 weeks for DLTs
Pharmacokinetics of AL2846 (in plasma)	In the study of single-dose, full PK profiles will be obtained at H0/H0.5/H1/H2/H4/H8/H11/H24/H34/H48/H58/H72/H96/H120/H168 (H means Hour). In the study of multiple-dose, full PK profiles will be obtained at D0/D1/D4/D7/D10/D13/D15/D18/D21/D24/D28 (D means Day).	up to 28 Days (endpoint when the two consecutive time points of blood drug concentration <150 DPM/mL)
The maximum tolerated dose (MTD) of AL2846	The highest dose at which no more than 33% of the subjects experience a dose-limiting toxicity (DLT) during treatment	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Percentage of participants with OR based assessment of confirmed complete remission (CR) or confirmed partial remission (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST).	each 56 days up to intolerance the toxicity or PD (up to 24 months)

Collaborators and Investigators

• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Anticipated): October 1, 2020
• Study Completion (Anticipated): October 1, 2020

Study Registration Dates

• First Submitted: May 16, 2016
• First Submitted That Met QC Criteria: May 18, 2016
• First Posted (Estimate): May 20, 2016

Study Record Updates

• Last Update Posted (Actual): May 21, 2019
• Last Update Submitted That Met QC Criteria: May 19, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: AL2846-I-0001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided