Tolerance and Pharmacokinetic Study of Chlorogenic Acid to Advanced Glioblastoma

Study Overview
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Brief Summary
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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 ;

Detailed Description
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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 ; Determine the human pharmacokinetics characteristic of Chlorogenic acid for injection; Preliminary observation the effectiveness and effective dose; Provide the basis for the dosage regimen of phase II/III.

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

Conditions
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Glioblastoma

Intervention / Treatment
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* Drug: Chlorogenic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with pathologic or/and FNAC confirmation of advanced glioblastoma(WHO,III-IV grade) but without effective treatment or with treatment failure; Between 18 and 65 years of age, KPS≥40; 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. Life expectancy of at least three (3) months at the enrollment; 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: Patients who have received large area radiotherapy （>30% marrow capacity）; Without pathologic or/and FNAC confirmation of advanced glioblastoma; Patients who has primary immunodeficiency diseases； 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.; Patients who have received the therapy of chemotherapy or radical radiotherapy within 4 weeks before enrollment; Patients who have used nitrosoureas drug or mitomycin within 6 weeks or tyrosine kinase inhibitor within 2 weeks before enrollment; Patients who have received therapy of major surgery within 4 weeks or biopsy surgery within 2 weeks before enrollment; Patients who experience grade 2 or more than grade 2 toxicity caused by the past therapies; Patients who have history of drug abuse; Uncontrollable psychopaths； Uncontrollable diabetes； Pregnant or breast-feeding women, or patients(male and female) who have pregnancy plan; 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; Known active hepatitis B/hepatitis C, positive HIV/ syphilis antibody; Patient who need long term treatment of cortical hormone or other immunosuppressive drugs such as visceral organ transplanters; Allergic to the investigational drug; Other patients judged ineligible for enrollment in the study by the investigator (sub-investigator). 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 .

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chlorgenic acid, Treatment, powder<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Maximum Tolerated Dose |  | 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 | Measure Description | 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 |