A Phase I Study of Anlotinib on Tolerance and Pharmacokinetics (ALTN)

Anlotibib (ALTN) is a kind of innovative medicines approved by State Food and Drug Administration（SFDA） which was researched by Jiangsu Chia-tai Tianqing Pharmaceutical Co., Ltd.

ALTN is a kinase inhibitor of receptor tyrosine with multi-targets, especially for VEGFR2 and VEGFR3. It has the obvious resistance to new angiogenesis.

Study Overview

• Status: Completed
• Conditions: Advanced Cancer
• Intervention / Treatment: Drug: anlotinib

Detailed Description

The primary objective of this trial is to explore the maximum tolerated dose(MTD), dose-limiting toxicity(DLT) of ALTN and rational dosage regimen for phase II study, to investigate the pharmacokinetics with single and multiple doses of ALTN from 5mg/d,10mg/d,16mg/d,12mg.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • 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:

1. late malignant tumor patients diagnosed with the pathological and/or cytological;
2. lack of the standard treatment or treatment failure;
3. 18-65years, ECOG:0-1,Expected survival period >3 months;
4. stop medicine > 30 days if any other chemotherapy drugs be used.
5. HB≥90g/L,ANC(Absolute Neutrophil Count) ≥1.5×109/L；PLT ≥100×109/L ,BIL/ALT/AST(aspartate aminotransferase )/Cr in normal range,or CCR≥60ml/min,TG≤ 3.0mmol/L，cholesterol≤7.75mmol/L; LVEF≥LLN.
6. Female should be agreed to use contraceptive during the study and after 6 months (such as intrauterine device(IUD), the pill or a condom); The serum or urine pregnancy test negative before take ALTN, and is out of non-lactation period. Male should be agreed to use contraceptive during the study and after the period of 6 months.
7. Volunteer, informed consent form (ICF) signed, compliance.

Exclusion Criteria:

1. Subject was diagnosed with other malignant tumors previously or meanwhile;
2. Participated in other clinical trials in four weeks;
3. Has influence of oral drugs(such as unable to swallow, gastrointestinal tract after resection);
4. Already diagnosed with brain metastases, spinal cord compression, cancerous meningitis, or screening CT or MRI findings of the brain or soft meningeal disease patient;
5. Hypertension
6. Urine protein: ++, and urinary in 24 hours > 1.0g;
7. Coagulant function abnormality: subject with bleeding tendency (such as active peptic ulcer) or are receiving thrombolysis or anticoagulant therapy;
8. Subject with psychiatric drugs abuse history and can't get rid of, or mental disorder;
9. With artery/venous thrombotic before oral ALTN;
10. With history of anticoagulant, vitamin K antagonists(such as warfarin or heparin) or other analogues treatment;
11. With Abnormal thyroid function;
12. With history of psychiatric drugs abuse or a mental disorder;
13. Viral hepatitis B or hepatitis c patients (including hepatitis b, hepatitis c virus carriers);
14. Have immunodeficiency history;
15. According to the researcher's judgment,there are concomitant diseases which will seriously endanger the patients or obstruct the patients to complete the clinical trial.

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: anlotinib; dosage form:capsule dosage:5mg,10mg,16mg,12mg frequency:once one day duration:Continuous two weeks then stop a week	Drug: anlotinib; oral medicine.; Other Names: ALTN

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax Cmax t1/2 AUC	To collect point with single drug:H0/H0.5/H1/H2/H4/H8/H12/H24/H48/H72/H96/H120/H144/H/H168/H192/H216/H240 To collect point with multiple drug:d1/d2/d4/d7/d10/d14/d15/d21/d22/d28/d35/d42	Up to 52 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	blood examination, urine examination, stool examination, blood biochemical (ALT, AST, TB(total bilirubin), DB, BUN, Cr, blood electrolyte), electrocardiogram (ecg), thyroid function, the function of blood coagulation, etc	Up to 21 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
tumor size	To evaluate the effectiveness of ALTN by enhanced CT scan every two cycles. Refer to recist 1.1.	Up to 42 days

Collaborators and Investigators

• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
• Collaborators: Nanjing Medical University
• Investigators: Principal Investigator: Yihebali Chi, doctor, Cancer Institude and hospital,CAMS

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: March 29, 2013
• First Submitted That Met QC Criteria: April 13, 2013
• First Posted (Estimate): April 17, 2013

Study Record Updates

• Last Update Posted (Estimate): October 28, 2015
• Last Update Submitted That Met QC Criteria: October 27, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Advanced cancer
• Other Study ID Numbers: ALTN-I-01