Digestive TumorNCT05673434
A Clinical Study on the Safety and Efficacy of CAR-T Therapy for the TM4SF1-positive Tumors of Digestive System
A study testing TM4SF1-positive chimeric antigen receptor T-cell therapy in people with Digestive Tumor, run by Changhai Hospital.
Trial summary
Transmembrane 4 L Six Family Member 1 (TM4SF1) is highly expressed in many tumors of digestive system . The Chimeric Antigen Receptor T-cells (CAR-T) that target TM4SF1 has been generated in our good manufacturing practices (GMP) facility and the anti-tumor effects have been demonstrated in multiple in vitro and in… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Digestive Tumor
- What is being tested?
- TM4SF1-positive chimeric antigen receptor T-cell therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- No sites listed yet
- Study dates
- 30 Jan 2023to 30 Jan 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The age at the time of signing the informed consent is ≥ 18 years old and ≤ 75 years old, regardless of gender;
- BMI ≥ 18.5 (weight (kg)/height (m ²）)；
- The physical condition score of the Eastern Cooperative Oncology Group (ECOG) is ≤ 2 points;
- The estimated survival time is not less than 12 weeks;
- Patients confirmed by histology or cytology, who progress after standard treatment failure, or cannot accept/fail patients with advanced solid tumors with standard treatment, such as gastric cancer, colorectal cancer, pancreatic cancer and other digestive system tumors.
- According to RECIST 1.1 standard, there is at least one measurable lesion, that is, according to CT or MRI cross section on imaging, the long diameter of non lymph node lesions ≥ 10 mm, or the short diameter of lymph node lesions ≥ 15 mm; measurable disease CT scanning of the longest axis of the focus ≥ 10 mm (CT scanning slice thickness ≤ 5 mm), and the measurable part should not be accepted local treatment such as radiotherapy (for lesions located in the previous radiotherapy area, if progress is confirmed, it is also optional target lesion);
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- It has suitable organs and hematopoietic function (It is not allowed to use any blood components, cytokines, leukemic agents, platelet promoting agents and human albumin preparations within 14 days before screening), according to the following laboratory tests:
- Color Doppler echocardiography showed normal diastolic function, left ventricular ejection fraction (LVEF) ≥ 50%, and no large amount of pericardial effusion
- Finger oxygen saturation>93%；
- Neutrophil (ANC) ≥ 1.5 × 10 9 /L；
- Platelet count≥75×10 9 /L；
- Hemoglobin (HGB)>90g/L；
- Absolute lymphocyte count (ALC)≥0.8×10 9 /L；
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the upper limit of normal value (ULN) in patients without liver metastasis and ≤ 3.5 times ULN in patients with liver metastasis;
- total bilirubin≤1.5 times ULN；
- Creatinine ≤ 1.5 times ULN;
- Prothrombin time (PT) or international normalized ratio(INR)<1.5 times ULN, and partial thromboplastin time (APTT)<1.5 times ULN.
- The expression of TM4SF1 is positive, which can be divided into two cases, and it can meet one of the following conditions：
- The tumor tissue samples with recurrence at the primary site or presence of the primary site and within 1 year were detected as high expression of TM4SF1 by immunohistochemistry;
- The high expression of TM4SF1 was detected by immunohistochemistry after biopsy in non primary tumor metastasis;
- Women of childbearing age must have negative pregnancy results during screening period and before drenching treatment.
- The subject voluntarily joined the group and signed the informed consent form, and voluntarily followed the trial treatment scheme and visit plan.
Who cannot join
- Subjects with allergic constitution and allergy to immunotherapy or related drugs；
- Adverse reactions of previous treatment failed to recover to CTCAE v5.0 grade ≤ 1 ；
- Patients expected to have major surgery during the study period, including the screening period;；
- Patients with severe autoimmune diseases requiring long-term (more than 2 months) systemic immunosuppressive therapy;；
- Any unstable systemic disease: including but not limited to unstable angina pectoris, cerebrovascular accident, transient cerebral ischemia (within 6 months before screening), myocardial infarction (within 6 months before screening), congestive heart failure（≥ NYHA Class III）, severe arrhythmia with poor drug control, liver, kidney or metabolic disease, and hypertension beyond control through standard treatment
- Known or suspected brain metastasis, including central nervous system and spinal cord compression or meningeal metastasis patient；
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- Other active malignant tumors in the past 5 years
- Patients with active bleeding and thrombotic disease requiring treatment;
- Patients with pleural and peritoneal effusion who cannot be controlled and need clinical treatment or intervention；
- Patients who used corticosteroid hormones (prednisone ≥ 20mg/day or other corticosteroid hormones with equivalent dose) and other immunosuppressants with pharmacological dose 7 days before cell collection and 5 days before cell reinfusion in this study；
- Alcohol dependent persons or those who have a history of drug abuse or drug abuse in the past one year；
- Subjects with any mental illness that may affect the understanding of informed consent；
- Patients with acute or chronic active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection; Patients with human immunodeficiency virus (HIV) antibody positive; Patients with treponema pallidum antibody test positive
Trial locations and contacts
No sites are listed yet.
About this study
Transmembrane 4 L Six Family Member 1 (TM4SF1) is highly expressed in many tumors of digestive system .
The Chimeric Antigen Receptor T-cells (CAR-T) that target TM4SF1 has been generated in our good manufacturing practices (GMP) facility and the anti-tumor effects have been demonstrated in multiple in vitro and in vivo studies.
Read more
Clinical studies are proposed here to evaluate the anti-tumor activity of these cell therapy products for treatment of patients with TM4SF1 positive tumors of digestive system. In this study, the safety, tolerance, and preliminary efficacy of CART-TM4SF1 cells will be examined in patients with refractory/recurrent advanced pancreatic cancer, colorectal cancer, gastric cancer or liver cancer.
Clinical and immunological responses will be evaluated about 30 days and last up to 2 years after CAR-T cell infusion.
Read the detailed description
Background:
While great progress has been made in CAR T-cell therapy for the treatment of hematologic malignancies, its use in solid tumors is still at the exploratory stage.Transmembrane 4 L Six Family Member 1 (TM4SF1) protein mediates signal transduction events that play a role in the regulation of cell development, activation, growth and motility. It is a cell surface antigen and is highly expressed in different carcinomas.The investigators have developed novel TM4SF1-targeting CAR T-cells (CART-TM4SF1 cells) for the treatment of digestive system tumors.
These engineered T-cells can target and kill the TM4SF1-positive tumor cells in vitro or in mice. Both of the CAR molecules contain a safety switch based on epidermal growth factor receptor (EGFR) to ensure the safety.The investigators propose to investigate the feasibility, safety, and efficacy of CART-TM4SF1 cells for digestive system tumors in patients.
Objectives:
Primary objectives:
- To determine the safety/tolerance dosages and adverse effects of CART-TM4SF1 cells cells in the treatment of TM4SF1-positive recurrent/refractory advanced tumors of digestive system.
- To preliminarily evaluate the efficacy of CART-TM4SF1 cells in the treatment of TM4SF1-positive recurrent/refractory advanced tumors of digestive system.
Secondary objectives:
- To determine the pharmacokinetic (PK)/pharmacodynamic (PD) characteristics of CART-TM4SF1 cells in humans.
- To evaluate the overall survival (OS) and tumor regression after treatment.
- To assess the life quality of patients
Study population:
The study population includes 12-24 patients with refractory/recurrent advanced digestive system tumors with positive expression of TM4SF1. The subjects will receive four incremental doses (3-6 subjects in each dose group), as well as safety and preliminary efficacy evaluation.
Design:
- This is a single-center open-label clinical study.
- Recruit patients with refractory/recurrent digestive system tumors, with written consent for this study. Perform biopsy to determine the expression of TM4SF1 of the tumor with immuno-histochemistry (IHC).
- Collect peripheral blood mononuclear cell (PBMC) from the patients, isolate and activate the T cells and transfect them with TM4SF1 targeting CAR, expand the transfected T cells as needed, assess the quality and antitumor activity of the CAR-T products in vitro and then transfer them back the patients via systemic or local injections, and follow up closely to collect related results as needed.
- Clinical and immunological responses will be evaluated closely in about 30 days and last up to 2 years after back-transfusion.
- Conditions
- Digestive Tumor
- Being tested
- TM4SF1-positive chimeric antigen receptor T-cell therapy
- Keywords
- Neoplasms
- Medical subject headings
- Digestive System Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TM4SF1-positive chimeric antigen receptor T-cell therapyBiological
Specification: 50mL/bag. Storage: The prepared CAR T-cells are cryopreserved in a preserving medium . This product is manufactured under the current good manufacture practices (cGMP) conditions, with restrictions on chemical components, free from animal- or human-derived components and confirming to the United States Pharmacopeia (USP)<71> and <85> regulations.
Preservation: The frozen CAR T-cells are preserved in the liquid nitrogen transfer tank.
Usage: The frozen CAR T-cells are preserved at low temperature and transferred to the bedside. The cells are thawed by 36 degrees centigrade to 38 degrees centigrade. water bath. The frozen cells are gently massaged until complete thawing. Then they are transfused back to the patients intravenously. The transfusion will be finished within 10-20 min.
| Study group | Role | What they receive |
|---|---|---|
| Experimental: TM4SF1 positive CAR-T cells for digestive tumors | Experimental | The present study is proposed to study advanced malignant digestive tumors in adults, and the four escalating doses, namely, 0.5~1.0.,1.0~2.0,2.0~3.0 and 3.0~10.0 (×10 ^6/kg), will be given.
Intervention: Biological: TM4SF1-positive chimeric antigen receptor T-cell therapy Receives: Biological: TM4SF1-positive chimeric antigen receptor T-cell therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety assessed by Incidence of Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
After CAR-T cell infusion,the investigators will observe the potential adverse events related to the CAR-T cells infusion such as high fever, kidney failure and so on.
Adverse events are coded according to MedDRA 22.0. List total number of AEs and SAEs; Number of subjects with different types of AEs and SAEs, case-times and incidence.AEs and SAEs are graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTC AE version 5.0).
Measured: 2 years
Secondary outcomes (2)
Overall response rate (ORR)
The ORR is defined as the percentage of participants who achieve partial response (PR) or better according to Response Evaluation Criteria In Solid Tumors（RECIST) criteria.
Measured: 2 years
CAR-T cell testing
The level of CAR-T cells will be tested regularly by Real-time Quantitative Polymerase Chain Reaction Detecting System(qPCR) or Flow cytometry to evaluate the proliferation in vivo and long-term survival
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2023
- Study start30 Jan 2023 (estimated)
- Primary completion30 Jul 2024 (estimated)
- Study completion30 Jan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Digestive TumorStudies of the same condition, open and under way.
- More trials run by Changhai HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Changhai Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai Ultra-T Immune Therapeutics Co. LTD
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05673434
- Sponsor's protocol ID
- CART-TM4SF1-01
- Status last verified
- Dec 2022
- First submitted
- 21 Dec 2022
- Last updated
- 6 Jan 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.
PubMed 30207593Park JW, Chen M, Colombo M, Roberts LR, Schwartz M, Chen PJ, Kudo M, Johnson P, Wagner S, Orsini LS, Sherman M. Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study. Liver Int. 2015 Sep;35(9):2155-66. doi: 10.1111/liv.12818. Epub 2015 Mar 25.
PubMed 25752327Sher YP, Lin SI, Chai KM, Chen IH, Liu SJ. Endoplasmic reticulum-targeting sequence enhanced the cellular immunity of a tumor-associated antigen L6-based DNA vaccine. Am J Cancer Res. 2019 Sep 1;9(9):2028-2036. eCollection 2019.
PubMed 31598403Gao C, Yao H, Liu H, Feng Y, Yang Z. TM4SF1 is a potential target for anti-invasion and metastasis in ovarian cancer. BMC Cancer. 2019 Mar 15;19(1):237. doi: 10.1186/s12885-019-5417-7.
PubMed 30876464Gao H, Chakraborty G, Zhang Z, Akalay I, Gadiya M, Gao Y, Sinha S, Hu J, Jiang C, Akram M, Brogi E, Leitinger B, Giancotti FG. Multi-organ Site Metastatic Reactivation Mediated by Non-canonical Discoidin Domain Receptor 1 Signaling. Cell. 2016 Jun 30;166(1):47-62. doi: 10.1016/j.cell.2016.06.009.
PubMed 27368100Martinez-Romero J, Bueno-Fortes S, Martin-Merino M, Ramirez de Molina A, De Las Rivas J. Survival marker genes of colorectal cancer derived from consistent transcriptomic profiling. BMC Genomics. 2018 Dec 11;19(Suppl 8):857. doi: 10.1186/s12864-018-5193-9.
PubMed 30537927Park YR, Kim SL, Lee MR, Seo SY, Lee JH, Kim SH, Kim IH, Lee SO, Lee ST, Kim SW. MicroRNA-30a-5p (miR-30a) regulates cell motility and EMT by directly targeting oncogenic TM4SF1 in colorectal cancer. J Cancer Res Clin Oncol. 2017 Oct;143(10):1915-1927. doi: 10.1007/s00432-017-2440-4. Epub 2017 May 20.
PubMed 28528497Ma YS, Yu F, Zhong XM, Lu GX, Cong XL, Xue SB, Xie WT, Hou LK, Pang LJ, Wu W, Zhang W, Cong LL, Liu T, Long HD, Sun R, Sun HY, Lv ZW, Wu CY, Fu D. miR-30 Family Reduction Maintains Self-Renewal and Promotes Tumorigenesis in NSCLC-Initiating Cells by Targeting Oncogene TM4SF1. Mol Ther. 2018 Dec 5;26(12):2751-2765. doi: 10.1016/j.ymthe.2018.09.006. Epub 2018 Sep 13.
PubMed 30301667Xue L, Yu X, Jiang X, Deng X, Mao L, Guo L, Fan J, Fan Q, Wang L, Lu SH. TM4SF1 promotes the self-renewal of esophageal cancer stem-like cells and is regulated by miR-141. Oncotarget. 2017 Mar 21;8(12):19274-19284. doi: 10.18632/oncotarget.13866.
PubMed 27974706Goodman GE, Hellstrom I, Yelton DE, Murray JL, O'Hara S, Meaker E, Zeigler L, Palazollo P, Nicaise C, Usakewicz J, et al. Phase I trial of chimeric (human-mouse) monoclonal antibody L6 in patients with non-small-cell lung, colon, and breast cancer. Cancer Immunol Immunother. 1993;36(4):267-73. doi: 10.1007/BF01740909.
PubMed 8382560Ziegler LD, Palazzolo P, Cunningham J, Janus M, Itoh K, Hayakawa K, Hellstrom I, Hellstrom KE, Nicaise C, Dennin R, et al. Phase I trial of murine monoclonal antibody L6 in combination with subcutaneous interleukin-2 in patients with advanced carcinoma of the breast, colorectum, and lung. J Clin Oncol. 1992 Sep;10(9):1470-8. doi: 10.1200/JCO.1992.10.9.1470.
PubMed 1517790Goodman GE, Hellstrom I, Brodzinsky L, Nicaise C, Kulander B, Hummel D, Hellstrom KE. Phase I trial of murine monoclonal antibody L6 in breast, colon, ovarian, and lung cancer. J Clin Oncol. 1990 Jun;8(6):1083-92. doi: 10.1200/JCO.1990.8.6.1083.
PubMed 2161448Denardo SJ, O'Grady LF, Richman CM, Goldstein DS, O'Donnell RT, Denardo DA, Kroger LA, Lamborn KR, Hellstrom KE, Hellstrom I, Denardo GL. Radioimmunotherapy for advanced breast cancer using I-131-ChL6 antibody. Anticancer Res. 1997 May-Jun;17(3B):1745-51.
PubMed 9179228Katz SC, Burga RA, McCormack E, Wang LJ, Mooring W, Point GR, Khare PD, Thorn M, Ma Q, Stainken BF, Assanah EO, Davies R, Espat NJ, Junghans RP. Phase I Hepatic Immunotherapy for Metastases Study of Intra-Arterial Chimeric Antigen Receptor-Modified T-cell Therapy for CEA+ Liver Metastases. Clin Cancer Res. 2015 Jul 15;21(14):3149-59. doi: 10.1158/1078-0432.CCR-14-1421. Epub 2015 Apr 7.
PubMed 25850950Saied A, Licata L, Burga RA, Thorn M, McCormack E, Stainken BF, Assanah EO, Khare PD, Davies R, Espat NJ, Junghans RP, Katz SC. Neutrophil:lymphocyte ratios and serum cytokine changes after hepatic artery chimeric antigen receptor-modified T-cell infusions for liver metastases. Cancer Gene Ther. 2014 Nov;21(11):457-62. doi: 10.1038/cgt.2014.50. Epub 2014 Oct 3.
PubMed 25277132
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Study on the Safety and Efficacy of CAR-T Therapy for the TM4SF1-positive Tumors of Digestive System
- ClinicalTrials.gov ID
- NCT05673434
- Acronym / sponsor ID
- CART-TM4SF1-01
- Conditions
- Digestive Tumor
- Keywords
- Neoplasms
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Changhai HospitalUniversity, hospital or other
- Collaborators
- Shanghai Ultra-T Immune Therapeutics Co. LTD
- Study start
- 30 Jan 2023 (estimated)
- Primary completion
- 30 Jul 2024 (estimated)
- Study completion
- 30 Jan 2025 (estimated)
- First posted
- 6 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Transmembrane 4 L Six Family Member 1 (TM4SF1) is highly expressed in many tumors of digestive system .
The Chimeric Antigen Receptor T-cells (CAR-T) that target TM4SF1 has been generated in our good manufacturing practices (GMP) facility and the anti-tumor effects have been demonstrated in multiple in vitro and in vivo studies.
Clinical studies are proposed here to evaluate the anti-tumor activity of these cell therapy products for treatment of patients with TM4SF1 positive tumors of digestive system. In this study, the safety, tolerance, and preliminary efficacy of CART-TM4SF1 cells will be examined in patients with refractory/recurrent advanced pancreatic cancer, colorectal cancer, gastric cancer or liver cancer.
Clinical and immunological responses will be evaluated about 30 days and last up to 2 years after CAR-T cell infusion.
Detailed description
Background:
While great progress has been made in CAR T-cell therapy for the treatment of hematologic malignancies, its use in solid tumors is still at the exploratory stage.Transmembrane 4 L Six Family Member 1 (TM4SF1) protein mediates signal transduction events that play a role in the regulation of cell development, activation, growth and motility. It is a cell surface antigen and is highly expressed in different carcinomas.The investigators have developed novel TM4SF1-targeting CAR T-cells (CART-TM4SF1 cells) for the treatment of digestive system tumors.
These engineered T-cells can target and kill the TM4SF1-positive tumor cells in vitro or in mice. Both of the CAR molecules contain a safety switch based on epidermal growth factor receptor (EGFR) to ensure the safety.The investigators propose to investigate the feasibility, safety, and efficacy of CART-TM4SF1 cells for digestive system tumors in patients.
Objectives:
Primary objectives:
- To determine the safety/tolerance dosages and adverse effects of CART-TM4SF1 cells cells in the treatment of TM4SF1-positive recurrent/refractory advanced tumors of digestive system.
- To preliminarily evaluate the efficacy of CART-TM4SF1 cells in the treatment of TM4SF1-positive recurrent/refractory advanced tumors of digestive system.
Secondary objectives:
- To determine the pharmacokinetic (PK)/pharmacodynamic (PD) characteristics of CART-TM4SF1 cells in humans.
- To evaluate the overall survival (OS) and tumor regression after treatment.
- To assess the life quality of patients
Study population:
The study population includes 12-24 patients with refractory/recurrent advanced digestive system tumors with positive expression of TM4SF1. The subjects will receive four incremental doses (3-6 subjects in each dose group), as well as safety and preliminary efficacy evaluation.
Design:
- This is a single-center open-label clinical study.
- Recruit patients with refractory/recurrent digestive system tumors, with written consent for this study. Perform biopsy to determine the expression of TM4SF1 of the tumor with immuno-histochemistry (IHC).
- Collect peripheral blood mononuclear cell (PBMC) from the patients, isolate and activate the T cells and transfect them with TM4SF1 targeting CAR, expand the transfected T cells as needed, assess the quality and antitumor activity of the CAR-T products in vitro and then transfer them back the patients via systemic or local injections, and follow up closely to collect related results as needed.
- Clinical and immunological responses will be evaluated closely in about 30 days and last up to 2 years after back-transfusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental: TM4SF1 positive CAR-T cells for digestive tumors | Experimental | Biological: TM4SF1-positive chimeric antigen receptor T-cell therapyThe present study is proposed to study advanced malignant digestive tumors in adults, and the four escalating doses, namely, 0.5~1.0.,1.0~2.0,2.0~3.0 and 3.0~10.0 (×10 ^6/kg), will be given. Intervention: Biological: TM4SF1-positive chimeric antigen receptor T-cell therapy |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- The age at the time of signing the informed consent is ≥ 18 years old and ≤ 75 years old, regardless of gender;
- BMI ≥ 18.5 (weight (kg)/height (m ²）)；
- The physical condition score of the Eastern Cooperative Oncology Group (ECOG) is ≤ 2 points;
- The estimated survival time is not less than 12 weeks;
- Patients confirmed by histology or cytology, who progress after standard treatment failure, or cannot accept/fail patients with advanced solid tumors with standard treatment, such as gastric cancer, colorectal cancer, pancreatic cancer and other digestive system tumors.
Key exclusion criteria (13 listed)
- Subjects with allergic constitution and allergy to immunotherapy or related drugs；
- Adverse reactions of previous treatment failed to recover to CTCAE v5.0 grade ≤ 1 ；
- Patients expected to have major surgery during the study period, including the screening period;；
- Patients with severe autoimmune diseases requiring long-term (more than 2 months) systemic immunosuppressive therapy;；
- Any unstable systemic disease: including but not limited to unstable angina pectoris, cerebrovascular accident, transient cerebral ischemia (within 6 months before screening), myocardial infarction (within 6 months before screening), congestive heart failure（≥ NYHA Class III）, severe arrhythmia with poor drug control, liver, kidney or metabolic disease, and hypertension beyond control through standard treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TM4SF1-positive chimeric antigen receptor T-cell therapySpecification: 50mL/bag. Storage: The prepared CAR T-cells are cryopreserved in a preserving medium . This product is manufactured under the current good manufacture practices (cGMP) conditions, with restrictions on chemical components, free from animal- or human-derived components and confirming to the United States Pharmacopeia (USP)<71> and <85> regulations. Preservation: The frozen CAR T-cells are preserved in the liquid nitrogen transfer tank. Usage: The frozen CAR T-cells are preserved at low temperature and transferred to the bedside. The cells are thawed by 36 degrees centigrade to 38 degrees centigrade. water bath. The frozen cells are gently massaged until complete thawing. Then they are transfused back to the patients intravenously. The transfusion will be finished within 10-20 min. | Biological | Experimental: TM4SF1 positive CAR-T cells for digestive tumors |
Primary outcome
Safety assessed by Incidence of Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: 2 years
After CAR-T cell infusion,the investigators will observe the potential adverse events related to the CAR-T cells infusion such as high fever, kidney failure and so on. Adverse events are coded according to MedDRA 22.0. List total number of AEs and SAEs; Number of subjects with different types of AEs and SAEs, case-times and incidence.AEs and SAEs are graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTC AE version 5.0).
2 secondary outcomes
Overall response rate (ORR)
Time frame: 2 years
CAR-T cell testing
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2023.
- Background: PubMed 30207593Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.
- Background: PubMed 25752327Park JW, Chen M, Colombo M, Roberts LR, Schwartz M, Chen PJ, Kudo M, Johnson P, Wagner S, Orsini LS, Sherman M. Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study. Liver Int. 2015 Sep;35(9):2155-66. doi: 10.1111/liv.12818. Epub 2015 Mar 25.
- Background: PubMed 31598403Sher YP, Lin SI, Chai KM, Chen IH, Liu SJ. Endoplasmic reticulum-targeting sequence enhanced the cellular immunity of a tumor-associated antigen L6-based DNA vaccine. Am J Cancer Res. 2019 Sep 1;9(9):2028-2036. eCollection 2019.
- Background: PubMed 30876464Gao C, Yao H, Liu H, Feng Y, Yang Z. TM4SF1 is a potential target for anti-invasion and metastasis in ovarian cancer. BMC Cancer. 2019 Mar 15;19(1):237. doi: 10.1186/s12885-019-5417-7.
- Background: PubMed 27368100Gao H, Chakraborty G, Zhang Z, Akalay I, Gadiya M, Gao Y, Sinha S, Hu J, Jiang C, Akram M, Brogi E, Leitinger B, Giancotti FG. Multi-organ Site Metastatic Reactivation Mediated by Non-canonical Discoidin Domain Receptor 1 Signaling. Cell. 2016 Jun 30;166(1):47-62. doi: 10.1016/j.cell.2016.06.009.
- Background: PubMed 30537927Martinez-Romero J, Bueno-Fortes S, Martin-Merino M, Ramirez de Molina A, De Las Rivas J. Survival marker genes of colorectal cancer derived from consistent transcriptomic profiling. BMC Genomics. 2018 Dec 11;19(Suppl 8):857. doi: 10.1186/s12864-018-5193-9.
- Background: PubMed 28528497Park YR, Kim SL, Lee MR, Seo SY, Lee JH, Kim SH, Kim IH, Lee SO, Lee ST, Kim SW. MicroRNA-30a-5p (miR-30a) regulates cell motility and EMT by directly targeting oncogenic TM4SF1 in colorectal cancer. J Cancer Res Clin Oncol. 2017 Oct;143(10):1915-1927. doi: 10.1007/s00432-017-2440-4. Epub 2017 May 20.
- Background: PubMed 30301667Ma YS, Yu F, Zhong XM, Lu GX, Cong XL, Xue SB, Xie WT, Hou LK, Pang LJ, Wu W, Zhang W, Cong LL, Liu T, Long HD, Sun R, Sun HY, Lv ZW, Wu CY, Fu D. miR-30 Family Reduction Maintains Self-Renewal and Promotes Tumorigenesis in NSCLC-Initiating Cells by Targeting Oncogene TM4SF1. Mol Ther. 2018 Dec 5;26(12):2751-2765. doi: 10.1016/j.ymthe.2018.09.006. Epub 2018 Sep 13.
- Background: PubMed 27974706Xue L, Yu X, Jiang X, Deng X, Mao L, Guo L, Fan J, Fan Q, Wang L, Lu SH. TM4SF1 promotes the self-renewal of esophageal cancer stem-like cells and is regulated by miR-141. Oncotarget. 2017 Mar 21;8(12):19274-19284. doi: 10.18632/oncotarget.13866.
- Background: PubMed 8382560Goodman GE, Hellstrom I, Yelton DE, Murray JL, O'Hara S, Meaker E, Zeigler L, Palazollo P, Nicaise C, Usakewicz J, et al. Phase I trial of chimeric (human-mouse) monoclonal antibody L6 in patients with non-small-cell lung, colon, and breast cancer. Cancer Immunol Immunother. 1993;36(4):267-73. doi: 10.1007/BF01740909.
- Background: PubMed 1517790Ziegler LD, Palazzolo P, Cunningham J, Janus M, Itoh K, Hayakawa K, Hellstrom I, Hellstrom KE, Nicaise C, Dennin R, et al. Phase I trial of murine monoclonal antibody L6 in combination with subcutaneous interleukin-2 in patients with advanced carcinoma of the breast, colorectum, and lung. J Clin Oncol. 1992 Sep;10(9):1470-8. doi: 10.1200/JCO.1992.10.9.1470.
- Background: PubMed 2161448Goodman GE, Hellstrom I, Brodzinsky L, Nicaise C, Kulander B, Hummel D, Hellstrom KE. Phase I trial of murine monoclonal antibody L6 in breast, colon, ovarian, and lung cancer. J Clin Oncol. 1990 Jun;8(6):1083-92. doi: 10.1200/JCO.1990.8.6.1083.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
A study testing TM4SF1-positive chimeric antigen receptor T-cell therapy in people with Digestive Tumor, run by Changhai Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xianbao Zhan, professor (+86 13501850100, zhanxianbao@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety assessed by Incidence of Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05673434, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2023.