Tolerance and Pharmacokinetic Study of Chlorogenic Acid to Advanced Glioblastoma

• ClinicalTrials.gov Identifier: NCT02728349
• Recruitment Status: Completed
• First Posted: April 5, 2016
• Last Update Posted: November 1, 2018
• Sponsor: Sichuan J.Z. Bio-chemical Science and Technology Development Co., Ltd
• Collaborator: Beijing Shijitan Hospital
• Information provided by (Responsible Party): Sichuan J.Z. Bio-chemical Science and Technology Development Co., Ltd

Study Description

Brief Summary:

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 ;

Condition or disease	Intervention/treatment	Phase
Glioblastoma	Drug: Chlorogenic acid	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1 Trial of Tolerance and Pharmacokinetic of Chlorogenic Acid for Injection in the Advanced Glioblastoma Patients
• Actual Study Start Date: April 12, 2016
• Actual Primary Completion Date: August 23, 2017
• Actual Study Completion Date: September 13, 2017

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Improvement in cancer-related symptoms [ Time Frame: Within 1 year after the first dose of chlorogenic acid ]
2. disease control rate(DCR) [ Time Frame: Within the first 30 days after the first dose of chlorogenic acid ]
3. objective response rate (ORR) [ Time Frame: Within the first 30 days after the first dose of chlorogenic acid ]
4. progress free survival(PFS) [ Time Frame: Within the first 30 days after the first dose of chlorogenic acid ]
5. overall survival (OS) [ Time Frame: Within the first 30 days after the first dose of chlorogenic acid ]
6. Improvement in quality of life [ Time Frame: Within 1 year after the first dose of chlorogenic acid ]

Other Outcome Measures:

1. Changing in number of red blood cell [ Time Frame: Within 1 year after the first dose of chlorogenic acid ]
2. Changing in cytokines in peripheral blood [ Time Frame: Within 1 year after the first dose of chlorogenic acid ]
3. Changing in level of hemoglobin [ Time Frame: Within 1 year after the first dose of chlorogenic acid ]
4. Changing in lymphocyte subsets [ Time Frame: Within 1 year after the first dose of chlorogenic acid ]

Eligibility Criteria

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

Criteria

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 .

Contacts and Locations

Locations

China

Beijing Shijitan Hospital,Capital Medical University

Beijing, China, 100038

Sponsors and Collaborators

Sichuan J.Z. Bio-chemical Science and Technology Development Co., Ltd

Beijing Shijitan Hospital

More Information

• Responsible Party: Sichuan J.Z. Bio-chemical Science and Technology Development Co., Ltd
• ClinicalTrials.gov Identifier: NCT02728349
• Other Study ID Numbers: LYS-I-03
• First Posted: April 5, 2016
• Last Update Posted: November 1, 2018
• Last Verified: November 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Glioblastoma; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue