Tolerance and Pharmacokinetic Study of Chlorogenic Acid to Advanced Glioblastoma

Phase 1 Trial of Tolerance and Pharmacokinetic of Chlorogenic Acid for Injection in the Advanced Glioblastoma Patients

The purpose of this study:

Determining the Maximum Tolerated Dose (MTD), Dose-Limiting Toxicity (DLT), pharmacokinetics characteristic, and dosage regimen of phase II/III of Chlorogenic acid for injection in the advanced Glioblastoma Patients ;

Study Overview

• Status: Completed
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: Chlorogenic acid

Detailed Description

1. Investigate the tolerance of Chlorogenic acid for injection in human body, determine the Maximum Tolerated Dose (MTD) and Dose-Limiting Toxicity (DLT) of Chlorogenic acid for injection in the advanced Glioblastoma Patients ;
2. Determine the human pharmacokinetics characteristic of Chlorogenic acid for injection;
3. Preliminary observation the effectiveness and effective dose;
4. Provide the basis for the dosage regimen of phase II/III.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100038
    • Beijing Shijitan Hospital,Capital Medical University

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. Patients with pathologic or/and FNAC confirmation of advanced glioblastoma(WHO,III-IV grade) but without effective treatment or with treatment failure;
2. Between 18 and 65 years of age, KPS≥40;
3. According to RANO(2010), the parents will be eligible if one of the following conditions apply: steroid dose increased or stable,the enhanced tumor lesion increased more than 25%; the unenhanced tumor lesion increased because of the progressive tumor,even if the lesion was unmeasurable.
4. Life expectancy of at least three (3) months at the enrollment;
5. Patients who have sufficient baseline organ function and whose laboratory data can meet the following criteria at the enrollment:

1)PLT count≥100×10~9/L, 2)WLB count≥4.0×10~9/L and ≤12×10~9/L, 3)Neutrophil granulocyte count≥2.0×10~9/L, 4)HGB count≥90g/L, 5)Total bilirubin <=1.5 times of ULN, 6)ALT/AST ≤2.5 times of ULN, 7)SCr≤1.5 times of ULN, 8)Normal ECG with LVEF (≥50%) measured by echocardiography; 6.Female patients with negative pregnant test, and male/female patients of reproductive age without pregnancy planning in the next 12 months; 7.Volunteered for the phase 1 trial and sign the informed consent without protest;

Exclusion Criteria:

1. Patients who have received large area radiotherapy （>30% marrow capacity）;
2. Without pathologic or/and FNAC confirmation of advanced glioblastoma;
3. Patients who has primary immunodeficiency diseases；
4. Patients who suffer from other serious complication, such as uncontrollable infection, myocardial infarction within the past 6 months at the enrollment , uncontrollable hypertension ,thromboembolism and etc.;
5. Patients who have received the therapy of chemotherapy or radical radiotherapy within 4 weeks before enrollment;
6. Patients who have used nitrosoureas drug or mitomycin within 6 weeks or tyrosine kinase inhibitor within 2 weeks before enrollment;
7. Patients who have received therapy of major surgery within 4 weeks or biopsy surgery within 2 weeks before enrollment;
8. Patients who experience grade 2 or more than grade 2 toxicity caused by the past therapies;
9. Patients who have history of drug abuse;
10. Uncontrollable psychopaths；
11. Uncontrollable diabetes；
12. Pregnant or breast-feeding women, or patients(male and female) who have pregnancy plan;
13. Patients who had received a therapy of another investigational drug within 12 weeks or patients who are still in another clinical trial at the enrollment;
14. Known active hepatitis B/hepatitis C, positive HIV/ syphilis antibody;
15. Patient who need long term treatment of cortical hormone or other immunosuppressive drugs such as visceral organ transplanters;
16. Allergic to the investigational drug;
17. Other patients judged ineligible for enrollment in the study by the investigator (sub-investigator).
18. Patients who have received the therapy of adrenal steroid hormones within 1 week before enrollment or will receive the therapy for a long period time，except for Corticosteroid nasal spray，Inhaled Steroid and Topical steroids .

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: Chlorgenic acid, Treatment, powder; Chlorogenic acid for injection(30mg/bottle) is white or off-white freeze-dried lump or powder,it can be easily dissolved in water, which solubility is 20%.

Drug: Chlorogenic acid; Chlorogenic acid for injection is polyphenols, micromolecular and un-endogenous substance. It might play the role of cancer treatment via balancing tumor micro-environmental immune status according to the stability and rationality of immunodeficiency and endogenous immune material expression around the tumor. Chlorogenic acid for injection is made from chlorogenic acid (purity≥98%) which is extracted from folium cortex eucommiae.Chlorogenic acid and its preparations have not been reported as chemical drug and marketed around the world.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Tolerated Dose	Within the first 30 days after the first dose of chlorogenic acid
Number of adverse events	Within the first 30 days after the first dose of chlorogenic acid
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0，grade ≥3 (DLT)	Within the first 30 days after the first dose of chlorogenic acid
Area under the plasma concentration versus time curve (AUC) of chlorogenic acid	Within the first 30 days after the first dose of chlorogenic acid
Peak Plasma Concentration (Cmax) of chlorogenic acid	Within the first 30 days after the first dose of chlorogenic acid

Secondary Outcome Measures

Outcome Measure	Time Frame
Improvement in cancer-related symptoms	Within 1 year after the first dose of chlorogenic acid
disease control rate(DCR)	Within the first 30 days after the first dose of chlorogenic acid
objective response rate (ORR)	Within the first 30 days after the first dose of chlorogenic acid
progress free survival(PFS)	Within the first 30 days after the first dose of chlorogenic acid
overall survival (OS)	Within the first 30 days after the first dose of chlorogenic acid
Improvement in quality of life	Within 1 year after the first dose of chlorogenic acid

Other Outcome Measures

Outcome Measure	Time Frame
Changing in number of red blood cell	Within 1 year after the first dose of chlorogenic acid
Changing in cytokines in peripheral blood	Within 1 year after the first dose of chlorogenic acid
Changing in level of hemoglobin	Within 1 year after the first dose of chlorogenic acid
Changing in lymphocyte subsets	Within 1 year after the first dose of chlorogenic acid

Collaborators and Investigators

• Sponsor: Sichuan J.Z. Bio-chemical Science and Technology Development Co., Ltd
• Collaborators: Beijing Shijitan Hospital, Capital Medical University

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2016
• Primary Completion (Actual): August 23, 2017
• Study Completion (Actual): September 13, 2017

Study Registration Dates

• First Submitted: March 28, 2016
• First Submitted That Met QC Criteria: March 30, 2016
• First Posted (Estimate): April 5, 2016

Study Record Updates

• Last Update Posted (Actual): November 1, 2018
• Last Update Submitted That Met QC Criteria: October 30, 2018
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: LYS-I-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No