Clinical trial NCT02728349: Tolerance and Pharmacokinetic Study of Chlorogenic Acid to Advanced Glioblastoma
Official title: Phase 1 Trial of Tolerance and Pharmacokinetic of Chlorogenic Acid for Injection in the Advanced Glioblastoma Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Glioblastoma
Lead sponsor: Sichuan J.Z. Bio-chemical Science and Technology Development Co., Ltd
Sponsor class: INDUSTRY
Collaborators: name: Beijing Shijitan Hospital, Capital Medical University
First posted: 2016-04-05
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 ;

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.

Eligibility 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 .

Primary outcomes:
measure: Number of adverse events
timeFrame: Within the first 30 days after the first dose of chlorogenic acid
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0，grade ≥3 (DLT)
timeFrame: Within the first 30 days after the first dose of chlorogenic acid
measure: Maximum Tolerated Dose
timeFrame: Within the first 30 days after the first dose of chlorogenic acid
measure: Area under the plasma concentration versus time curve (AUC) of chlorogenic acid
timeFrame: Within the first 30 days after the first dose of chlorogenic acid
measure: Peak Plasma Concentration (Cmax) of chlorogenic acid
timeFrame: Within the first 30 days after the first dose of chlorogenic acid
Secondary outcomes:
measure: Improvement in cancer-related symptoms
timeFrame: Within 1 year after the first dose of chlorogenic acid
measure: disease control rate(DCR)
timeFrame: Within the first 30 days after the first dose of chlorogenic acid
measure: objective response rate (ORR)
timeFrame: Within the first 30 days after the first dose of chlorogenic acid
measure: progress free survival(PFS)
timeFrame: Within the first 30 days after the first dose of chlorogenic acid
measure: overall survival (OS)
timeFrame: Within the first 30 days after the first dose of chlorogenic acid
measure: Improvement in quality of life
timeFrame: Within 1 year after the first dose of chlorogenic acid
Other outcomes:
measure: Changing in number of red blood cell
timeFrame: Within 1 year after the first dose of chlorogenic acid
measure: Changing in cytokines in peripheral blood
timeFrame: Within 1 year after the first dose of chlorogenic acid
measure: Changing in level of hemoglobin
timeFrame: Within 1 year after the first dose of chlorogenic acid
measure: Changing in lymphocyte subsets
timeFrame: Within 1 year after the first dose of chlorogenic acid
Locations:
city: Beijing
country: China
facility: Beijing Shijitan Hospital,Capital Medical University
Study officials:
References: