Studies of Chlorogenic Acid for Injection for Safety and Efficacy of Grade IV GBM Patients

Study Overview
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Brief Summary
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The purpose of phase II/III study: Determining the Overall Survival（OS）of Chlorogenic acid for injection comparing to in the advanced Glioblastoma Patients through study completion（an average of 18 months）after the first dose of chlorogenic acid for injection and Lomustine.

Detailed Description
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Chlorogenic acid (CHA) is a class 1 innovative small molecular natural drug, developed by Sichuan Jiuzhang Biological Science and Technology Co., Ltd. The mechanism of broad-spectrum antitumor activity is immunoregulation. After received the clinical trial approval issued by CFDA, Jiuzhang Biotech successfully finished the phase I clinical studies of CHA for injection in advanced GBM patients, focus on safety, PK, and preliminary efficacy evaluation. The results of phase I data showed that CHA had good safety, the main adverse effect was induration, no other serious adverse effects. PK exhibited that CHA had a rapid metabolism character (t1/2 = 1-1.5 h). In addition, there were no accumulative side effects for long-term use. To the investigators' surprise, the preliminary efficacy evaluation was amazing, there were 1 case CR and 1 case PR. The median OS of grade IV GBM patients was 21.4 months in effective dose group, which was much better than that of the historical reported data.The purpose of phase II/III study: Determining the Overall Survival（OS）of Chlorogenic acid for injection comparing to in the advanced Glioblastoma Patients through study completion（an average of 18 months）after the first dose of chlorogenic acid for injection and Lomustine .

Official Title
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A Randomized, Control, Open-label, Multicenter, Phase II/III Studies of Chlorogenic Acid for Injection for Safety and Efficacy of Grade IV GBM Patients

Conditions
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GBM

Intervention / Treatment
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* Drug: Chlorogenic acid for Injection
* Drug: Lomustine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18; KPS ≥ 60; Recurrent GBM; Estimated lifetime ≥ 3 months； Female patients with negative pregnant test, and male/female patients of reproductive age without pregnancy planning in the next 12 months; Volunteered for the phase 2 trial and sign the informed consent without protest. Exclusion Criteria: Patients who have received the therapy of chemotherapy or radical radiotherapy within 1 month before enrollment; 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 1 month； Known active hepatitis B/hepatitis C, positive HIV/ syphilis antibody; Patients who have received therapy of major surgery within 4 weeks or biopsy surgery within 1 week before enrollment; Patient who need long term treatment of cortical hormone or other immunosuppressive drugs such as visceral organ transplanters； Patients who have sufficient baseline organ function and whose laboratory data can meet the following criteria at the enrollment:1)PLT count<80×10 9/L； 2)NEUT# count<1.5×10 9/L ；3)HGB count<90g/L；4)Total bilirubin >1.5 times of ULN；5)ALT/AST >1.5 times of ULN； History of drug abuse； Patients who was treated with Immunologic drugs（DC/CIK/CTL/PD-（L）1） in 3 months; Patients who are false progressers； Patients who can not be received MRI examination； Patients who had severe trauma or infectious diseases within 4 weeks； Patients who had cerebral stroke or Transient ischemic attack within 6 months； Patients who were performed important operations within 4 weeks； Uncontrollable psychopaths; Patients who had other advanced cancers within 5 years； Patients who had grade III or IV heart failure within 6 months； Other patients judged ineligible for enrollment in the study by the investigator (sub-investigator).

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chlorogenic Acid for Injection<br>3 mg/kg per day, injection for 28 days，5 weeks per circle; max. 8 circles | Drug: Chlorogenic acid for Injection<br>* Chlorogenic acid (CHA) is a class 1 innovative small molecular natural drug, developed by Sichuan Jiuzhang Biological Science and Technology Co., Ltd. The mechanism of broad-spectrum antitumor activity is immunoregulation.<br>* Other names: CHA;|
| Active Comparator: Lomustine<br>110 mg/m2 taken as a single oral dose every 6 weeks; max. 4 circles | Drug: Lomustine<br>* Lomustine (INN), abbreviated as CCNU (original brand name (formerly available) is CeeNU, now marketed as Gleostine), is an alkylating nitrosourea compound used in chemotherapy. It is closely related to semustine and is in the same family as streptozotocin. It is a highly lipid-soluble drug, thus it crosses the blood-brain barrier. This property makes it ideal for treating brain tumors, which is its primary use.<br>* Other names: CCNU;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival（OS） |  | Through study completion（an average of 18 months）after the first dose of chlorogenic acid for injection and Lomustine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progress free survival(PFS) |  | Through study completion（an average of 18 months）after the first dose of chlorogenic acid for injection and Lomustine | 
| disease control rate（DCR) |  | Within the first 10 weeks after the first dose of chlorogenic acid for injection and Lomustine | 
| objective response rate (ORR) |  | Within the first 10 weeks after the first dose of chlorogenic acid for injection and Lomustine | 
| Karnofsky score standard |  | Through study completion（an average of 18 months）after the first dose of chlorogenic acid for injection and Lomustine | 
| Montreal Cognitive Assessment score standard |  | Through study completion（an average of 18 months）after the first dose of chlorogenic acid for injection and Lomustine |