Plasmodium Immunotherapy for Breast and Liver Cancers

Sponsor

CAS Lamvac Biotech Co., Ltd. (Industry)

Overall Status

Unknown status

CT.gov ID

NCT03474822

Collaborator

(none)

Enrollment

Location

Arm

40.7

Anticipated Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and preliminarily evaluate the effectiveness of Plasmodium immunotherapy for advanced breast cancers and advanced liver cancers.The treatment will last 4-6 weeks from the day of successful infection and will be terminated by antimalarial drugs.

Condition or Disease	Intervention/Treatment	Phase
Advanced Breast Cancer Advanced Liver Cancer	Biological: Blood-stage infection of P.vivax	Phase 1/Phase 2

Detailed Description

This study is to enroll 30 patients in each type of cancer. Each patient will be vaccinated with P.vivax-infected red blood cells containing approximately 0.1-1.0 × 10^7 Plasmodium parasites and be observed for the exact infection time, parasitemia condition and infection course; principal clinical symptoms such as fever; gastrointestinal reaction; peripheral blood parameters; the changes in heart, lung, liver and kidney function. Preliminarily observe the changes in the primary and metastatic lesions of the cancer, the tolerance of patients to Plasmodium infection, changes in tumor-related parameters and immunological related parameters.The rate of the erythrocytes infected by plasmodium is controlled below 0.01% by using Artemisinin during the course, and clinical treatment is conduced according to the microscopic examination to ensure that no serious complications occurs.The duration of the planned treatment of each subject is 4-6 weeks. The time of the treatment course is based on vaccination with P.vivax-infected red blood cells. After 4-6 weeks, parasitemia will be terminated by antimalarial drugs for terminating the treatment of Plasmodium immunotherapy (the immunological treatment effect may persist after the termination of Plasmodium infection), and then the patients are followed up for 2 years.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Clinical Study of Plasmodium Immunotherapy for Advanced Breast Cancers and Advanced Liver Cancers

Actual Study Start Date :

Aug 10, 2018

Anticipated Primary Completion Date :

Dec 31, 2021

Anticipated Study Completion Date :

Dec 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Blood-stage infection of P.vivax This is a single arm study that plans to enroll 30 patients in each type cancer and each patient will be vaccinated with P.vivax-infected red blood cells containing approximately 0.1-1.0 × 10^7 Plasmodium parasites. The treatment will last 4-6 weeks from the day of successful infection and will be terminated by antimalarial drugs.	Biological: Blood-stage infection of P.vivax The P. vivax infected blood will be confirmed to follow the national standard of blood donation to ensure that only P. vivax is included, excluding the presence of P. falciparum. Exclude other infectious diseases according to the test of national standard of blood donation.

Arm

Intervention/Treatment

Experimental: Blood-stage infection of P.vivax

This is a single arm study that plans to enroll 30 patients in each type cancer and each patient will be vaccinated with P.vivax-infected red blood cells containing approximately 0.1-1.0 × 10^7 Plasmodium parasites. The treatment will last 4-6 weeks from the day of successful infection and will be terminated by antimalarial drugs.

Biological: Blood-stage infection of P.vivax

The P. vivax infected blood will be confirmed to follow the national standard of blood donation to ensure that only P. vivax is included, excluding the presence of P. falciparum. Exclude other infectious diseases according to the test of national standard of blood donation.

Outcome Measures

Primary Outcome Measures

Number of participants with treatment-related adverse events as assessed by NCI CTCAE 4.0 [2 years]
Adverse events will be evaluated according to NCI CTCAE 4.0, and the incidence of adverse events will be calculated.

Secondary Outcome Measures

Progression free survival (PFS) [2 years]
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).
Overall survival [2 years]
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 [2 years]
The patient's sensitive tumor markers will be reviewed periodically from the time they are enrolled into the study.
Objective response rate (ORR) [2 years]
The proportion of patients whose tumor is reduced to a certain amount and maintain a certain period of time.
Quality of life [2 years]
Patients are regularly filled with QLQ-C30 (cancer patient quality of life scale) to assess the quality of life of the patients.
1 year of survival rate [2 years]
The number of cancer cases remaining after 1 year of treatment / the total number of cancer cases treated * 100%.
2 year of survival rate [2 years]
The number of cancer cases remaining after 2 years of treatment / the total number of cancer cases treated * 100%.
Immunological index [2 years]
Detection of absolute number of immune cells（such as CD3+CD4+、CD3+CD8+ and so on）in peripheral blood by flow cytometry.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

18-70 years of age, male or female.
Patients with advanced breast cancer and advanced liver cancer confirmed by histopathology and imaging; and imaging lesions of the tumor are clear and measurable.
Previously received at least one standard therapy.
The time interval of the termination of chemotherapy (including interventional chemotherapy) or radiotherapy is at least 1 months for patients who had received chemotherapy or radiotherapy; at least 5 half-life for patients who had received targeted drug therapy (the half-life of targeted drug is according to the drug instructions).
ECGO score of 0 or 1;
Expected survival ≥ 6 months;
PLT ≥100× 10^{9/L, NE ≥ 1.5 × 10}9/L, and HGB ≥ 100 g/L; no significant morphological abnormalities of red blood cells, or anemia (iron deficiency anemia, autoimmune hemolytic anemia, thalassemia, etc.).
The peripheral blood count of immune cells is close to normal or normal, the immune function test result is close to or at the level of normal population, and the function of heart, lung, liver and kidney are basically normal (the liver function classification of Child-push is A or B, Cr≤1.5×ULN);
Patient compliance meets the need for follow-up;
The subjects are able to understand and sign informed consent.

Exclusion Criteria:

Patients with severe hemoglobin disease or severe G6PD deficiency;
Patients with splenectomy or splenomegaly;
Patients with drug addiction or alcohol dependence;
With the following diseases or conditions: serious or uncontrolled systemic disease or any unstable systemic diseases (including but not limited to active infection, grade three hypertension, unstable angina, congestive heart failure, class III or IV heart disease, severe arrhythmia, liver and kidney dysfunction or metabolic disease), a clear history of neurological or psychiatric disorders, etc.
Accept any other anti-tumor treatment at the same time.
Patients with significantly lower immune function than those in the normal population.
Lung function is seriously damaged, the MNW <39% or can't get out of bed, still feel short of breath when resting.
Advanced liver cancer patients with severe varicose vein in the esophagus.
Rough cough, dyspnea, without normal diet or difficult to cooperate.
Poor body condition, the researchers assess that the patients can't tolerate the immune therapy.
Pregnant or lactating women.
Women of childbearing age with positive result for pregnancy tests.
Any case that researchers believe that the patient does not suit for this clinical study.