Clinical trial NCT02873390: PD-1 Antibody Expressing CAR-T Cells for EGFR Family Member Positive Advanced Solid Tumor
Official title: A Clinical Study of PD-1 Antibody Expressing CAR-T Cells for EGFR Family Member Positive Advanced Solid Tumor
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: PD-1 Antibody
CAR-T Cells
Advanced Malignancies
Keywords: PD-1 Antibody
CAR-T Cells
EGFR family
Advanced Malignancies
Lead sponsor: Ningbo Cancer Hospital
Sponsor class: INDUSTRY
First posted: 2016-08-19
Enrollment: 20
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: To evaluate the safety and effectiveness of cell therapy using herinCAR-PD1 cells to treat advanced cancer.

Individuals greater than or equal to 18 years of age and less than or equal to 70 years of age who have been diagnosed with relapsed or refractory cancer that has not responded to or has relapsed after standard treatment.

Detailed description: A total of 20 patients may be enrolled over a period of 1-2 years.

Eligibility criteria: Inclusion Criteria:

1. Age 18\~80 years old, male or female;
2. Life expectancy≥6 months;
3. ECOG score: 0-2;
4. Advanced Solid Tumor were diagnosed by histology and cytology;
5. Enough venous channel,no other contraindications to the separation and collection of white blood cells;
6. Immunohistochemistry and RT-PCR technology will be used to determine the positive EGFR family (including EGFR, HER2, HER4) and EGFRVIII、IGF1R protein. At least one protein expressed in immunohistochemical tumor tissue should be no less than grade 2 or 2+ scores. The levels of protein are defined as follows: (according to cell staining) : grade 0: without staining; grade 1: 1-25%; grade 2: 26-50% and grade 3: 51-100%; (According to the intensity): negative; 1+; 2+ and 3+;
7. Laboratory examination: white blood cell≥3 x 10\*9/L, blood platelet count≥60 x10\*9/L, hemoglobin≥85g/L; lymphocyte ≥0.7×109/L, total bilirubin less than 2.5 times of the normal level; ALT and AST less than 2.5 times of the normal level; serum creatinine less than 1.5 times of the normal level；
8. Signed informed consent；
9. Women of child-bearing age must have evidence of negative pregnancy test and be willing to practice birth control after 4 months following the cells transfusion.
10. Disease progression and the current treatment is invalid.
11. The treatment effect is not ideal after receiving 2 line therapy at least and willing to join in clinical trials

Exclusion Criteria:

1. Expected Overall survival \< 6 months;
2. Patients with uncontrolled hypertension,unstable coronary disease (uncontrolled arrhythmias, unstable angina, decompensated congestive heart failure (\> Class II, NYHA), or myocardial infarction within 6 months.
3. Abnormal lung function: FEV (forced expiratory volume) \< 30% prediction, DLCO (diffusing capacity of the lung for carbon monoxide) \< 30% prediction, blood oxygen saturation \< 90%;
4. Other serious diseases: nervous, mental disorders, immune regulatory diseases, metabolic diseases, infectious diseases, etc;
5. Unable or unwilling to provide informed consent, or fail to comply with the test requirements.
6. Uncontrolled active infection.
7. Serious chronic disease of critical organs such as kidney and liver. Kidney function more than CKD stage I,and liver function less than the Child - Pugh class B;
8. Long-term use or being used of immunosuppressive drugs with autoimmune diseases
9. Glucocorticoid is needed in a long term.
10. Currently (within 30 days) enrolled in another clinical trial.
11. Pregnancy or breastfeeding women.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: 2 years
measure: Disease control rate,(DCR)
timeFrame: 2 years
measure: Overall survival
timeFrame: 2 years
measure: Progress-free survival(PFS)
timeFrame: 2 years
Secondary outcomes:
measure: Quality of life
timeFrame: 2 years
Other outcomes:
Locations:
city: Ningbo
country: China
facility: Ningbo No.5 Hospital (Ningbo Cancer Hospital)
state: Zhejiang
Study officials:
affiliation: Ningbo No.5 Hospital (Ningbo Cancer Hospital)
name: Jiangtao Wang
role: STUDY_DIRECTOR
affiliation: Shanghai Cell Therapy Research Institute
name: Huajun Jin
role: STUDY_CHAIR
affiliation: Shanghai Cell Therapy Research Institute
name: Qijun Qian
role: STUDY_CHAIR
References: