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Plasmodium Immunotherapy for Advanced Ovarian Cancer

Primary Purpose

Advanced Ovarian Cancer

Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Plasmodium immunotherapy
Sponsored by
CAS Lamvac (Guangzhou) Biomedical Technology Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Ovarian Cancer focused on measuring Advanced ovarian cancer, Plasmodium immunotherapy, Plasmodium vivax

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Subjects must meet all the following inclusion criteria: 18-80 years old(including the threshold), female; The patients with ovarian cancer, who has been diagnosed by histopathological examination, can provide pathological reports, and is classified as stage III or stage IV according to the American Joint Committee on Cancer (AJCC) ovarian cancer staging version 8 (2017); Platinum-resistant patient who has received at least the first line of platinum-containing standard chemotherapy (refer to China's Guidelines for the Diagnosis and Treatment of Ovarian Cancer (2022)) in the past, and have been evaluated as disease progression by objective imaging; According to the evaluation standard of solid tumor efficacy RECIST 1.1, the therapeutic effect can be evaluated if there is ≥ 1 measurable lesion or continuous positive tumor marker; There are no plans and requirements for receiving other anti-tumor treatment during the treatment of Plasmodium immunotherapy; The score of Eastern Cooperative Oncology Group(ECOG) is 0-1; Expected survival time ≥ 3 months; If no platelets or red blood cells are transfused within 14 days before screening, and no thrombopoietin (TPO), granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), interleukin 11 (IL-11) or other drugs are used to correct abnormal blood picture: neutrophil (NEUM) ≥ 1.5 × 10^9/L, platelet (PLT) ≥ 100 × 10^9/L, hemoglobin (HGB) ≥ 90g/L, no obvious abnormality of erythrocyte morphology; Albumin (ALB) ≥ 35g/L; For female subjects with the possibility of pregnancy: from the time of signing the informed consent form (ICF) to the end of Plasmodium immunotherapy treatment at least 24 weeks, consent to abstinence or use of effective contraceptive methods, including intrauterine devices, etc. (Note: women of childbearing age have undergone surgical sterilization (including hysterectomy, bilateral oophorectomy or total hysterectomy), or have menopause for more than 24 menstrual cycles, That is, there is no possibility of pregnancy); Subjects are fully capable of understanding and signing the informed consent form. Exclusion Criteria: Subjects who have any of the following conditions cannot be included in the study: Have received any investigational drug within 4 weeks before the first inoculation of Plasmodium parasite, or have participated in another clinical study at the same time (except that the subjects have participated in the observational and non-interventive clinical study, or are in the follow-up period of the intervention clinical study); Immunodeficiency diseases, including HIV infection, other acquired and congenital immunodeficiency diseases; Coagulation dysfunction, or acute or chronic hemorrhagic disease; Have received other anti-tumor treatment in the past, and the period from the termination of treatment to the screening is less than 14 days or 5 half-lives (whichever occurs first); The time interval between radiotherapy and treatment in this study for patients who have previously received external or internal radiotherapy is less than 28 days; Patients with severe hemoglobinopathy or severe Glucose-6-Phosphate Dehydrogenase(G6PD) deficiency; After splenectomy or splenomegaly; Drug addicts or alcohol addicts; Plenty of pleural effusion, pericardial effusion or ascites; Patients with active hepatitis B or hepatitis C; Patients with obvious defects in immunocyte classification test (CD4+T cell absolute count<200/ μ l); Or receive any form of immunosuppressive treatment within 28 days before the trial treatment; Have serious or uncontrolled systemic diseases (including but not limited to active infection, grade III hypertension, unstable angina pectoris, congestive heart failure, grade III or IV heart disease, serious arrhythmia, liver and kidney insufficiency, myocardial infarction, etc.); Currently has mental disorder or a history of mental illness; Having undergone major surgery within three months from the screening period; Have received bone marrow transplantation or organ transplantation in the past; Moderate or severe pulmonary ventilation dysfunction; Those who are currently receiving regular anti-tumor treatment, and the treatment is effective or there is no obvious progress in the disease; The investigator evaluated the patients who could not tolerate Plasmodium immunotherapy; Pregnancy, lactation or pregnancy within 6 months after treatment; According to the judgment of the researcher, the other conditions of the subject are not suitable for participating in the test.

Sites / Locations

  • The Third Affiliated Hospital of Southern Medical University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Plasmodium immunotherapy group

Arm Description

This is a single arm study that is planed to enroll 30 patients with advanced ovarian cancer and each patient will be inoculated with P.vivax-infected red blood cells containing approximately 1-5 × 10^6 Plasmodium parasites. And successful infection will be indicated by microscopic observation of parasitemia in peripheral blood samples. The treatment will last 6 weeks from the day of successful infection and will be terminated by antimalarial drugs.

Outcomes

Primary Outcome Measures

Objective response rate(ORR)
The proportion of patients whose tumors shrink to a certain amount and remain for a certain time.
Progression-free survival (PFS)
Starting from treatment until the disease progression is first found or the time of any cause of death (disease progression refers to tumor growth, or metastasis of primary tumor, or discovery of new lesions).
Disease control rate (DCR)
The proportion of patients who had a best response rating of complete response, partial response, or stable disease.
1-year survival rate
The number of cancer cases remaining after 1 year of treatment / the total number of cancer cases treated * 100%.
2-year survival rate
The number of cancer cases remaining after 2 years of treatment / the total number of cancer cases treated * 100%.
Overall survival (OS)
The time starting from the treatment to death of whatever causes (when subjects have lost for follow-up before death, the last follow-up time will be calculated as the time of death).
Tumor marker level
The patient's sensitive tumor markers will be reviewed periodically from the time they are enrolled into the study. The tumor markers include Carcinoembryonic antigen(CEA), Carbohydrate Antigen 125(CA125), human epididymis protein 4(HE4), alpha-fetal protein(AFP), neuron-specific enolase(NSE), Carbohydrate Antigen 199(CA199).

Secondary Outcome Measures

Incidence of adverse events (AE) and serious adverse events (SAE)
Any adverse medical event occurred in the subjects who participated in the clinical study and received Plasmodium immunotherapy.
Quality of life score
Patients are regularly filled with Quality of Life Questionnaire-Core 30(QLQ-C30) to assess the quality of life of the patients.
Pain score
Patients are regularly evaluated with Visual Analog Scale for Pain. The minimum value is 0, and the maximum value is 10. The higher scores mean a worse outcome.

Full Information

First Posted
June 19, 2023
Last Updated
October 22, 2023
Sponsor
CAS Lamvac (Guangzhou) Biomedical Technology Co., Ltd.
Collaborators
The Third Affiliated Hospital of Southern Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT05924776
Brief Title
Plasmodium Immunotherapy for Advanced Ovarian Cancer
Official Title
Clinical Study of Plasmodium Immunotherapy for Advanced Ovarian Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 20, 2023 (Anticipated)
Primary Completion Date
November 30, 2026 (Anticipated)
Study Completion Date
March 30, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CAS Lamvac (Guangzhou) Biomedical Technology Co., Ltd.
Collaborators
The Third Affiliated Hospital of Southern Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The main purpose of this study is to evaluate the safety and effectiveness of Plasmodium immunotherapy in the treatment of advanced ovarian cancer. This study plans to enroll 30 patients with advanced ovarian cancer. Each patient is inoculated with Plasmodium vivax 1-5 × 10^6, observe the time when the parasite is detected in the peripheral blood of the subjects after the inoculation of Plasmodium, the change of the parasite density in the peripheral blood of the whole treatment cycle and the control effect of the drug on the parasite density, the main clinical symptoms and signs, laboratory test indicators, immunological test indicators and changes in the quality of life. To evaluate the safety and tolerance of the subjects to Plasmodium immunotherapy, as well as the changes of tumor related indicators and immunological indicators.
Detailed Description
Each subject who passed the screening is immunized with Plasmodium vivax 1-5 × 10^6, observe the time when the parasite is detected in the peripheral blood of the subjects after inoculation, the change of the parasite density in the peripheral blood of the whole treatment cycle (about 6 weeks) and the control effect of the drug on the parasite density. The clinical symptoms and signs after treatment are mainly observed; Blood routine, blood biochemistry, blood coagulation, tumor markers and other laboratory test indicators change; Changes of cellular immunity and humoral immunity; Changes in quality of life. When Plasmodium infected erythrocytes among total erythrocytes (defined as the parasite density) ≥ 0.1% occurs during the test, artemisinin drugs should be used to control the parasite density below 0.1%, and symptomatic treatment should be carried out. The duration of Plasmodium immunotherapy for each subject is 6 weeks (time window, ± 1 day). The day the immunodynamic marker (Fim) is greater than baseline level is defined as the first day of Plasmodium immunotherapy. When Plasmodium immunotherapy lasts for 6 weeks (time window, ± 1 day), use antimalarial drugs to kill the parasite and terminate the treatment. After treatment, the patients are followed up for 2 years. We will carry out a follow-up visit once a month after the termination of Plasmodium infection according to the plan, and the follow-up visit in the first month, third month and sixth month is outpatient visit, which is ± 5 days in the first month and ± 7 days in the third month and sixth month respectively; Follow-up outpatient visit will be conducted every 3 months ± 10 days; The rest are telephone follow-up (once every 30 days ± 5). When the follow-up time overlaps with the previous outpatient follow-up time, no additional telephone follow-up will be conducted.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Ovarian Cancer
Keywords
Advanced ovarian cancer, Plasmodium immunotherapy, Plasmodium vivax

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Plasmodium immunotherapy group
Arm Type
Experimental
Arm Description
This is a single arm study that is planed to enroll 30 patients with advanced ovarian cancer and each patient will be inoculated with P.vivax-infected red blood cells containing approximately 1-5 × 10^6 Plasmodium parasites. And successful infection will be indicated by microscopic observation of parasitemia in peripheral blood samples. The treatment will last 6 weeks from the day of successful infection and will be terminated by antimalarial drugs.
Intervention Type
Biological
Intervention Name(s)
Plasmodium immunotherapy
Intervention Description
Inoculation 1-5 × 10^6 Plasmodium vivax once
Primary Outcome Measure Information:
Title
Objective response rate(ORR)
Description
The proportion of patients whose tumors shrink to a certain amount and remain for a certain time.
Time Frame
2 years
Title
Progression-free survival (PFS)
Description
Starting from treatment until the disease progression is first found or the time of any cause of death (disease progression refers to tumor growth, or metastasis of primary tumor, or discovery of new lesions).
Time Frame
2 years
Title
Disease control rate (DCR)
Description
The proportion of patients who had a best response rating of complete response, partial response, or stable disease.
Time Frame
2 years
Title
1-year survival rate
Description
The number of cancer cases remaining after 1 year of treatment / the total number of cancer cases treated * 100%.
Time Frame
1 years
Title
2-year survival rate
Description
The number of cancer cases remaining after 2 years of treatment / the total number of cancer cases treated * 100%.
Time Frame
2 years
Title
Overall survival (OS)
Description
The time starting from the treatment to death of whatever causes (when subjects have lost for follow-up before death, the last follow-up time will be calculated as the time of death).
Time Frame
2 years
Title
Tumor marker level
Description
The patient's sensitive tumor markers will be reviewed periodically from the time they are enrolled into the study. The tumor markers include Carcinoembryonic antigen(CEA), Carbohydrate Antigen 125(CA125), human epididymis protein 4(HE4), alpha-fetal protein(AFP), neuron-specific enolase(NSE), Carbohydrate Antigen 199(CA199).
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Incidence of adverse events (AE) and serious adverse events (SAE)
Description
Any adverse medical event occurred in the subjects who participated in the clinical study and received Plasmodium immunotherapy.
Time Frame
2 years
Title
Quality of life score
Description
Patients are regularly filled with Quality of Life Questionnaire-Core 30(QLQ-C30) to assess the quality of life of the patients.
Time Frame
2 years
Title
Pain score
Description
Patients are regularly evaluated with Visual Analog Scale for Pain. The minimum value is 0, and the maximum value is 10. The higher scores mean a worse outcome.
Time Frame
2 years
Other Pre-specified Outcome Measures:
Title
Immunological indicators
Description
Detection of absolute number of immune cells(such as CD3+CD4+、CD3+CD8+ and so on)in peripheral blood by flow cytometry.
Time Frame
2 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects must meet all the following inclusion criteria: 18-80 years old(including the threshold), female; The patients with ovarian cancer, who has been diagnosed by histopathological examination, can provide pathological reports, and is classified as stage III or stage IV according to the American Joint Committee on Cancer (AJCC) ovarian cancer staging version 8 (2017); Platinum-resistant patient who has received at least the first line of platinum-containing standard chemotherapy (refer to China's Guidelines for the Diagnosis and Treatment of Ovarian Cancer (2022)) in the past, and have been evaluated as disease progression by objective imaging; According to the evaluation standard of solid tumor efficacy RECIST 1.1, the therapeutic effect can be evaluated if there is ≥ 1 measurable lesion or continuous positive tumor marker; There are no plans and requirements for receiving other anti-tumor treatment during the treatment of Plasmodium immunotherapy; The score of Eastern Cooperative Oncology Group(ECOG) is 0-1; Expected survival time ≥ 3 months; If no platelets or red blood cells are transfused within 14 days before screening, and no thrombopoietin (TPO), granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), interleukin 11 (IL-11) or other drugs are used to correct abnormal blood picture: neutrophil (NEUM) ≥ 1.5 × 10^9/L, platelet (PLT) ≥ 100 × 10^9/L, hemoglobin (HGB) ≥ 90g/L, no obvious abnormality of erythrocyte morphology; Albumin (ALB) ≥ 35g/L; For female subjects with the possibility of pregnancy: from the time of signing the informed consent form (ICF) to the end of Plasmodium immunotherapy treatment at least 24 weeks, consent to abstinence or use of effective contraceptive methods, including intrauterine devices, etc. (Note: women of childbearing age have undergone surgical sterilization (including hysterectomy, bilateral oophorectomy or total hysterectomy), or have menopause for more than 24 menstrual cycles, That is, there is no possibility of pregnancy); Subjects are fully capable of understanding and signing the informed consent form. Exclusion Criteria: Subjects who have any of the following conditions cannot be included in the study: Have received any investigational drug within 4 weeks before the first inoculation of Plasmodium parasite, or have participated in another clinical study at the same time (except that the subjects have participated in the observational and non-interventive clinical study, or are in the follow-up period of the intervention clinical study); Immunodeficiency diseases, including HIV infection, other acquired and congenital immunodeficiency diseases; Coagulation dysfunction, or acute or chronic hemorrhagic disease; Have received other anti-tumor treatment in the past, and the period from the termination of treatment to the screening is less than 14 days or 5 half-lives (whichever occurs first); The time interval between radiotherapy and treatment in this study for patients who have previously received external or internal radiotherapy is less than 28 days; Patients with severe hemoglobinopathy or severe Glucose-6-Phosphate Dehydrogenase(G6PD) deficiency; After splenectomy or splenomegaly; Drug addicts or alcohol addicts; Plenty of pleural effusion, pericardial effusion or ascites; Patients with active hepatitis B or hepatitis C; Patients with obvious defects in immunocyte classification test (CD4+T cell absolute count<200/ μ l); Or receive any form of immunosuppressive treatment within 28 days before the trial treatment; Have serious or uncontrolled systemic diseases (including but not limited to active infection, grade III hypertension, unstable angina pectoris, congestive heart failure, grade III or IV heart disease, serious arrhythmia, liver and kidney insufficiency, myocardial infarction, etc.); Currently has mental disorder or a history of mental illness; Having undergone major surgery within three months from the screening period; Have received bone marrow transplantation or organ transplantation in the past; Moderate or severe pulmonary ventilation dysfunction; Those who are currently receiving regular anti-tumor treatment, and the treatment is effective or there is no obvious progress in the disease; The investigator evaluated the patients who could not tolerate Plasmodium immunotherapy; Pregnancy, lactation or pregnancy within 6 months after treatment; According to the judgment of the researcher, the other conditions of the subject are not suitable for participating in the test.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xia Shuqi, B.S.
Phone
86-13602467407
Email
xia_shuqi@cas-lamvac.com
First Name & Middle Initial & Last Name or Official Title & Degree
Cao Jiazhen, B.S.
Phone
86-18520532361
Email
cao_jiazhen@cas-lamvac.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guo Shuiqun, Ph.D., M.D.
Organizational Affiliation
The Third Affiliated Hospital of Southern Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Third Affiliated Hospital of Southern Medical University
City
Guangzhou
State/Province
Guangdong
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guo Shunqun, Ph.D., M.D.
Email
guosq2005@126.com
First Name & Middle Initial & Last Name & Degree
Deng Yuanrun, Ph.D., M.D.
Email
295333202@qq.com

12. IPD Sharing Statement

Plan to Share IPD
No

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Plasmodium Immunotherapy for Advanced Ovarian Cancer

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