Safety and Efficacy Evaluation of MUC-1 CART in the Treatment of Intrahepatic Cholangiocarcinoma

NCT03633773 | Unknown Phase 1

• 1 other identifier: SAHZJU-Y2018-078
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Intrahepatic cholangiocarcinoma (ICC) is one of the most common liver malignancies. Surgical treatment is the first choice. However, for patients without surgical indications, the benefits of conventional chemoradiotherapy are limited. CART is one of the fastest developed treatments in recent years. MUC-1 CART can target abnormal glycosylation of MUC-1 and then killing tumor specifically. Here, investigators intend to evaluate the safety and efficacy of MUC-1 CART in intrahepatic cholangiocarcinoma.

Conditions

Intrahepatic Cholangiocarcinoma

Keywords

ICC; Mucin-1; CAR-T; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Disease control rate

  Percentage of patients whose cancer doesn't progress after treatment

  Up to approximately 12 months

Secondary Outcomes (9)

• Objective response rate

  Up to approximately 12 months

• Duration of overall response

  Up to approximately 12 months

• Progression-free survival

  Up to approximately 12 months

• Overall survival

  Up to approximately 12 months

• Common Toxicity Criteria for Adverse Effects

  Up to approximately 12 months

Study Arms (1)

MUC-1 CART

EXPERIMENTAL

Patients are given fludarabine and cyclophosphamide as pretreatment before MUC-1 CART immunotherapy. After treatment, specific antibodies, CART cells and serum levels of cytokines will be assessed.

Biological: MUC-1 CART cell immunotherapy

Interventions

MUC-1 CART cell immunotherapy BIOLOGICAL

After fludarabine and cyclophosphamide pre-chemotherapy，MUC-1 CART immunotherapy is given. A decent interval later, levels of specific antibodies, CART cells and serum cytokines will be assessed.

MUC-1 CART

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-65 years old.
• The expression of ST glycosylated MUC-1 was more than 1+ in immunohistochemistry(IHC) by applicant-approved laboratory.
• Histopathology or cytology confirmed intrahepatic cholangiocarcinoma.
• Patients who are unable to perform surgery or are not suitable for surgery, or who have recurrence after surgery, or who are unwilling to undergo chemotherapy.
• With at least one extracranial measurable lesion according to RECIST 1.1 edition.
• The expected survival time is more than 60 days.
• The main organs are functional and meet the following criteria:
• \) ECOG physical fitness score was 0\~1 or KPS score \>70. 2) Routine blood tests were in accordance with the following criteria: HB (\>90 g/L) (no blood transfusion within 14 days), ANC (\>1.5 x10\^9/L), PLT (\> 80 x10\^9/L), lymphocyte (\> 0.7 x10\^9/L), LY (\> 15%), Alb (\> 2.8 g/dL), serum lipase and amylase \< 1.5\^ULN (upper limit of normal value).
• \) Biochemical examination should meet the following criteria: TBIL \< 1.5x ULN (upper limit of normal value); ALT \< 2.5 xULN; serum Cr\<1 xULN; endogenous creatinine clearance \> 50ml/min (Cockcroft-Gault formula).
• \) Cardiac ejection fraction \>55%. 8. No active hemorrhagic disease or severe coagulation dysfunction. 9. No allergy to the contrast media. 10. Women of childbearing age must undergo a pregnancy test (serum or urine) within 7 days before enrollment, and the results are negative, and are willing to use appropriate contraception methods during the experiment and 8 weeks after the last CART.
• \. The volunteers voluntarily joined the study, signed informed consent, and had good compliance and follow-up.

You may not qualify if:

• The transduction efficiency of T cells was \<10% or T cells expanded less than 5 times after culture.
• Chimeric antigen receptor therapy or other transgenic T cell therapy.
• Pregnant or lactating women.
• In the first 4 weeks before the start of the study, they took part in other drug clinical trials.
• Patients with hypertension who can not be well controlled by a single antihypertensive drug (SBP\> 140 mmHg, DBP\> 90 mmHg), myocarditis or congenital heart disease, myocardial ischemia or infarction above grade I, arrhythmia above grade I (including QT interval \< 440 ms) or cardiac insufficiency.
• Long term unhealed wounds or fractures.
• With a history of psychotropic substance abuse and unable to quit or have a history of mental disorders.
• Past and current objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, severe impairment of lung function, etc.
• With uncontrollable fungi, bacteria, viruses or other infections, or need antibacterial treatment. The presence of simple urinary tract infections and uncomplicated bacterial pharyngitis is allowed after consultation with a medical supervisor, if there is a response to active therapy.
• According to the NCI-CTCAE 4.0 standard, the patients who had used chemotherapy in the past had grade 2 hematological toxicity or grade 3 non-hematological toxicity.
• With a history of HIV or hepatitis B or hepatitis C virus infection.
• There are any indwelling catheters or drainage tubes (e.g. percutaneous nephrostomy, Frey's catheter, bile drainage or pleural/peritoneal/pericardial catheter). The use of dedicated central venous catheters is permitted.
• With brain metastases.
• With a history or disease of CNS, such as epileptic seizures, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving CNS.
• With a major immunodeficiency.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

The second affiliated hospital of Zhejiang University

Hangzhou, Zhejiang, 310009, China

RECRUITING

MeSH Terms

Conditions

Cholangiocarcinoma; Medullary cystic kidney disease 1

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Central Study Contacts

Tingbo Liang, MD PhD

CONTACT

8613666676128; liangtingbo@zju.edu.cn

Qi Zhang, MD

CONTACT

8613819137113; zhangqi86@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2018
• First Posted: August 16, 2018
• Study Start: July 1, 2018
• Primary Completion: August 31, 2023
• Study Completion: December 31, 2024
• Last Updated: August 22, 2018

Record last verified: 2018-08

Locations

CN (1)