Clinical trial NCT03474822: Plasmodium Immunotherapy for Breast and Liver Cancers
Official title: Clinical Study of Plasmodium Immunotherapy for Advanced Breast Cancers and Advanced Liver Cancers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Breast Cancer
Advanced Liver Cancer
Keywords: Advanced breast cancer
advanced liver cancer
Plasmodium immunotherapy
Plasmodiun vivax
Lead sponsor: CAS Lamvac Biotech Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-03-23
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
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 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by NCI CTCAE 4.0
timeFrame: 2 years
Secondary outcomes:
measure: Progression free survival (PFS)
timeFrame: 2 years
measure: Overall survival
timeFrame: 2 years
measure: Tumor marker level
timeFrame: 2 years
measure: Objective response rate (ORR)
timeFrame: 2 years
measure: the Score of Quality of life
timeFrame: 2 years
measure: 1 year of survival rate
timeFrame: 2 years
measure: 2 year of survival rate
timeFrame: 2 years
measure: Immunological index
timeFrame: 2 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Plasmodiun vivax
state: Guangdong
Study officials:
References:
citation: Chen L, He Z, Qin L, Li Q, Shi X, Zhao S, Chen L, Zhong N, Chen X. Antitumor effect of malaria parasite infection in a murine Lewis lung cancer model through induction of innate and adaptive immunity. PLoS One. 2011;6(9):e24407. doi: 10.1371/journal.pone.0024407. Epub 2011 Sep 9.
citation: Qin L, Chen C, Chen L, Xue R, Ou-Yang M, Zhou C, Zhao S, He Z, Xia Y, He J, Liu P, Zhong N, Chen X. Worldwide malaria incidence and cancer mortality are inversely associated. Infect Agent Cancer. 2017 Feb 14;12:14. doi: 10.1186/s13027-017-0117-x. eCollection 2017.
citation: Yang Y, Liu Q, Lu J, Adah D, Yu S, Zhao S, Yao Y, Qin L, Qin L, Chen X. Exosomes from Plasmodium-infected hosts inhibit tumor angiogenesis in a murine Lewis lung cancer model. Oncogenesis. 2017 Jun 26;6(6):e351. doi: 10.1038/oncsis.2017.52.
citation: Liu Q, Yang Y, Tan X, Tao Z, Adah D, Yu S, Lu J, Zhao S, Qin L, Qin L, Chen X. Plasmodium parasite as an effective hepatocellular carcinoma antigen glypican-3 delivery vector. Oncotarget. 2017 Apr 11;8(15):24785-24796. doi: 10.18632/oncotarget.15806.