Clinical trial NCT04652219: CART Therapy in GUCY2C-positive Digestive Tract Tumors
Official title: Clinical Study on the Safety and Efficacy of CART Cells in the Treatment of Advanced GUCY2C-positive Digestive Tract Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Malignant Neoplasms of Digestive Organs
Keywords: cart
gucy2c
Digestive tract tumor
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Innovative Cellular Therapeutics Co., Ltd.
First posted: 2020-12-03
Enrollment: 1
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: Ict-gc is an open, single-center study to evaluate the safety and efficacy of CAR-T-targeted therapy in patients with advanced gastrointestinal tumors.

Detailed description: The primary objective of phase 1 is to evaluate the safety of CART regimens. The primary objective of phase 2 is to evaluate the efficacy of CART, as measured by objective response rate in subjects with colorectal cancer. Secondary objectives will include assessing the safety and tolerability of CART and additional efficacy endpoints.

Eligibility criteria: Inclusion Criteria:

1. Aged between 18 and 70; 2. Positive expression of immunohistochemical (IHC) assay targets in a laboratory approved by the partner; 3. Pathology confirmed digestive tract tumor; 4. Patients who have failed or relapsed after at least the first and second line standard treatment, and patients who are intolerant to or voluntarily give up the standardized treatment; 5. At least one extracranial measurable lesion according to RECIST1.1 or EORTC or PERCIST; 6. Expected survival ≥90 days; 7. The main organs are functioning normally, i.e. they meet the following criteria:

1. ECOG physical condition score is 0\~1 or KPS score is \>70;
2. serum test criteria were as follows: HB≥90g/L (no blood transfusion within 14 days), ANC≥ 1.5 x 10\^9/L, PLT≥80 x 10\^9/L, Alb ≥ 2.8g/dL, serum lipase and amylase \< 1.5×ULN (upper limit of normal value).
3. Biochemical examination shall meet the following standards: TBIL≤ 1.5x ULN (upper limit of normal value); ALT and AST≤ 2.5x ULN; ALT and AST≤5xULN in case of liver metastasis; Serum Cr≤1xULN, endogenous creatinine clearance rate \>50 ml/min (Cockcroft-Gault formula);
4. cardiac ejection fraction \>55%; 8. No hemorrhagic disease or coagulation disorder; 9. No allergy to the developer; 10. Women of childbearing age must undergo a pregnancy test (serum or urine) within 7 days prior to enrollment, with negative results, and be willing to use an appropriate method of contraception during and 8 weeks after the last dose of CART (women who have undergone sterilization or have been postmenopausal for at least 2 years may be considered sterile); 11. The subjects voluntarily joined the study, signed the informed consent form, had good compliance and cooperated with the follow-up.

Exclusion Criteria:

1. T cell transduction efficiency \<5% or T cell amplification \< 2 times after culture;
2. Participated in other drug clinical trials within 4 weeks before the start of the study;
3. Patients with hypertension and unable to obtain good control by single antihypertensive drugs (systolic blood pressure \> 140 mmHg, diastolic blood pressure b\> 90 mmHg, the specific conditions shall be evaluated by the researchers) have myocardial ischemia or infarction of grade I or above, arrhythmia of grade I or above (including QT interval ≥ 440ms) or cardiac insufficiency;
4. A wound or fracture in the chest or other area that has not healed for a long time;
5. Has a history of substance abuse and is unable to quit or has a history of mental disorders;
6. Patients with past or present objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radioactive pneumonia, drug-related pneumonia, severe pulmonary function impairment, etc.;
7. Fungus, bacteria, virus or other infection that cannot be controlled or requires antibiotic treatment. The presence of a simple urinary tract infection and uncomplicated bacterial pharyngitis is permitted after consultation with a medical supervisor;
8. For subjects who have used chemotherapy before, according to NCI-CTCAE 4.0, there is grade ≥2 hematological toxicity or grade ≥3 non-hematological toxicity at the time of enrollment;
9. A known history of HIV, or a positive nucleic acid test for hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive);
10. The presence of any indwered catheter or drainage tube (e.g., bile drainage tube or pleural/peritoneal/pericardial catheter). The use of specialized central venous catheters was permitted (the influence of fistula, percutaneous nephrostomy, and indwsed Foley catheters in colorectal cancer patients was considered by the investigators);
11. Brain metastases; A history or medical condition of CNS, such as seizure disorder, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving CNS;

13. Significant immunodeficiency; 14. The major therapeutic drugs in this study (including fludalabine, cyclophosphamide, sodium meth, and tozumab and anti-infective drugs used to prevent and treat CRS) have a history of severe hypersensitivity reaction; 15. History of deep vein thrombosis or pulmonary embolism 6 months before enrollment; 16. A history of an autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) that has resulted in injury to the terminal organs or that requires systemic immunosuppressive/disease-modulating drugs in the past 2 years; 17. Any disease that may interfere with the evaluation of the safety or efficacy of the study treatment.

Primary outcomes:
measure: Number of participants with CAR-T treatment-related adverse events as assessed by CTCAE v4.03
timeFrame: 24 months
Secondary outcomes:
measure: The event of cytokine release syndrome was reported using the grading scale in the protocol.
timeFrame: 24 months
measure: Efficacy will be assessed according to RECIST1.1 or EORTC or PERCIST criteria.
timeFrame: 24 months
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: First affiliated hospital, Zhejiang University
state: Zhejiang
Study officials:
affiliation: First Affiliated Hospital,Zhejiang University
name: Weijia Fang
role: PRINCIPAL_INVESTIGATOR
References: