Mesothelin-positive Advanced Refractory Solid TumorsPhase 1NCT05531708
Exploratory Study of Novel MSLN CAR-T Cell Therapy in Patients With MSLN-positive Advanced Refractory Solid Tumors
A Phase 1 study testing Anti-mesothelin CAR-T cells, Fludarabine and Cyclophosphamide in people with Mesothelin-positive Advanced Refractory Solid Tumors, run by Shanghai Pudong Hospital at 1 site in China.
Trial summary
This is a single-arm, open-label, exploratory clinical study to evaluate the safety and efficacy of novel Mesothelin CAR-T in patients with Mesothelin-positive advanced refractory solid tumors. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Mesothelin-positive Advanced Refractory Solid Tumors
- What is being tested?
- Anti-mesothelin CAR-T cells, Fludarabine and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteChina
- Study dates
- 2 Apr 2021to 30 Apr 2026
- Phase
- Phase 1
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Solid tumors positive for the Mesothelin antigen by Immunohistochemistry/Immunocytochemistry (IHC/ICC); histological diagnosis of malignancy refractory to, or relapsing after standard therapy.
- At least one measurable lesion according to RECIST v1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy ≥ 3 months.
- Neutrophils ≥ 1.0×10^9/L; Lymphocytes ≥ 0.5×10^9/L; Hemoglobin ≥ 80 g/L; Platelets ≥ 75×10^9/L.
- Adequate hepatic, renal, cardiac and coagulation function defined as:
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- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN); patients with liver metastasis must be ≤ 5 × ULN;
- Total bilirubin (TBIL) ≤ 1.5 × ULN; TBIL of patients with Gilbert's Syndrome must less than 3.0 mg/dL;
- Serum creatinine (Cr) ≤ 1.5 × ULN, and creatinine clearance rate (Ccr) ≥ 60 mL/min;
- Left ventricular ejection fraction (LVEF) > 45%;
- Prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
- Negative screen for infectious disease markers including HIV-Ab, HCV-Ab, HBeAg, HBsAg, and syphilis. Note - Participants with history of prior HBV infection are eligible if the HBV viral load is undetectable. Participants with a history of HCV infection who were treated for hepatitis C and cured are eligible if hepatitis C viral load is undetectable.
- The toxicities from any prior therapy must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo) according to NCI CTCAE v5.0.
- The washout period of previous treatment:
- Cytotoxic chemicals, monoclonal antibodies or immunotherapy should be washed out for at least 4 weeks before leukapheresis; anti-CTLA-4 antibodies should be washed out for at least 6 weeks;
- Systemic corticosteroids or other immunosuppressive therapies should be washed out for at least 2 weeks before leukapheresis;
- Biologicals or other approved molecular targeted inhibitors should be eluted for at least 1 week or 5 half-lives (whichever is longer) prior to leukapheresis.
- Participants must be able to understand the protocol and be willing to enroll the study, sign the informed consent, and be able to comply with the study and follow-up procedures.
Who cannot join
- Patients with central nervous system involvement.
- Patients with clinically significant systemic disease (such as: severe active infection or significant cardiac, pulmonary, hepatic, nervous system, or other organ dysfunction) that evaluated by the investigator would impair the patient's ability to tolerate the treatments used in this study or significantly increase the risk of complications.
- Any known or suspected autoimmune disease; or active, chronic or recurrent immune-mediated disease (within one year prior to enrollment) requiring steroid or other immunosuppressive therapy.
- History of severe systemic hypersensitivity reaction to the drugs/ingredients used in this study.
- Have received any allogeneic tissue/organ transplantation (including bone marrow transplantation, stem cell transplantation, liver transplantation, kidney transplantation), except for the transplantation that does not require immunosuppressive therapy (such as: corneal transplantation, hair transplantation.)
- Have received any genetic engineering modified T cell therapy (including CAR-T, TCR-T).
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- History of major surgery and unrecovered severe trauma within 4 weeks prior to signing informed consent.
- History of another malignancy tumor, except for non-melanoma skin cancer and carcinoma in situ of bladder, stomach, colon, cervix/dysplasia, melanoma, or breast.
- History of neuropsychiatric diseases diagnosed by the ICD-11 criteria or evaluated by investigator.
- For any other reasons, the patients are believed not suitable for participation in this study by investigators.
Trial locations and contacts
1 site in 1 country.
China1 site
Shanghai Pudong Hospital, Fudan University Affiliated Pudong Medical Center
Shanghai, Shanghai Municipality, 201399
About this study
Official title: Safety and Efficacy Study of Novel Mesothelin CAR-T Cell Therapy in Patients With Mesothelin-positive Advanced Refractory Solid Tumors
This is a single-arm, open-label, exploratory clinical study to evaluate the safety and efficacy of novel Mesothelin CAR-T in patients with Mesothelin-positive advanced refractory solid tumors.
- Being tested
- Anti-mesothelin CAR-T cells, Fludarabine, Cyclophosphamide
- Keywords
- Anti-mesothelin CAR-T, Solid tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-mesothelin CAR-T cellsBiological
D0: Anti-mesothelin CAR-T cells are autologous genetically modified T cells. Cells will be infused intravenously.
FludarabineDrug
Also called Fludara
D-7 to D-3: Fludarabine (25 mg/m^2/day) will be administered intravenously for 5 days.
CyclophosphamideDrug
Also called Cytoxan
D-7 and D-6: Cyclophosphamide (60 mg/kg/day) will be administered intravenously for 2 days.
| Study group | Role | What they receive |
|---|---|---|
| Anti-mesothelin CAR-T cells | Experimental | A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, anti-mesothelin CAR-T cells. Receives: Biological: Anti-mesothelin CAR-T cells; Drug: Fludarabine; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
TEAEs
Incidence and severity of treatment emergent adverse events.
Measured: 4 weeks after the CAR-T cells infusion
TRAEs
Incidence and severity of treatment related adverse events.
Measured: 4 weeks after the CAR-T cells infusion
AESIs
Incidence and severity of AEs of special interest.
Measured: 4 weeks after the CAR-T cells infusion
Secondary outcomes (2)
Objective Response Rate (ORR) (PR+CR)
The proportion of participants with complete response(CR) or partial response(PR) as measured by RECIST 1.1 criteria.
Measured: 12 weeks
Duration of Overall Response（DOR）
Time from documentation of disease response to disease progression.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2022
- Study start2 Apr 2021
- Primary completion30 Apr 2025 (estimated)
- Study completion30 Apr 2026 (estimated)
Why it stopped: The study is not initiated and we want it to be withdrawn.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mesothelin-positive Advanced Refractory Solid TumorsStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shanghai Pudong Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- UTC Therapeutics Inc.
- Responsible party
- Sponsor
- Investigators
- Zhiguo Long, Principal investigator, Shanghai Pudong Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05531708
- Sponsor's protocol ID
- 2021-IIT-004-E02
- Status last verified
- Feb 2023
- First submitted
- 22 Aug 2022
- Last updated
- 1 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy Study of Novel Mesothelin CAR-T Cell Therapy in Patients With Mesothelin-positive Advanced Refractory Solid Tumors
- ClinicalTrials.gov ID
- NCT05531708
- Acronym / sponsor ID
- 2021-IIT-004-E02
- Keywords
- Anti-mesothelin CAR-T, Solid tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The study is not initiated and we want it to be withdrawn.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Shanghai Pudong HospitalUniversity, hospital or other
- Collaborators
- UTC Therapeutics Inc.
- Study start
- 2 Apr 2021 (actual)
- Primary completion
- 30 Apr 2025 (estimated)
- Study completion
- 30 Apr 2026 (estimated)
- First posted
- 8 Sep 2022 (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.
This is a single-arm, open-label, exploratory clinical study to evaluate the safety and efficacy of novel Mesothelin CAR-T in patients with Mesothelin-positive advanced refractory solid tumors.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Anti-mesothelin CAR-T cells | Experimental | Biological: Anti-mesothelin CAR-T cells, Drug: Fludarabine, Drug: CyclophosphamideA conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, anti-mesothelin CAR-T cells. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Solid tumors positive for the Mesothelin antigen by Immunohistochemistry/Immunocytochemistry (IHC/ICC); histological diagnosis of malignancy refractory to, or relapsing after standard therapy.
- At least one measurable lesion according to RECIST v1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy ≥ 3 months.
- Neutrophils ≥ 1.0×10^9/L; Lymphocytes ≥ 0.5×10^9/L; Hemoglobin ≥ 80 g/L; Platelets ≥ 75×10^9/L.
Key exclusion criteria (10 listed)
- Patients with central nervous system involvement.
- Patients with clinically significant systemic disease (such as: severe active infection or significant cardiac, pulmonary, hepatic, nervous system, or other organ dysfunction) that evaluated by the investigator would impair the patient's ability to tolerate the treatments used in this study or significantly increase the risk of complications.
- Any known or suspected autoimmune disease; or active, chronic or recurrent immune-mediated disease (within one year prior to enrollment) requiring steroid or other immunosuppressive therapy.
- History of severe systemic hypersensitivity reaction to the drugs/ingredients used in this study.
- Have received any allogeneic tissue/organ transplantation (including bone marrow transplantation, stem cell transplantation, liver transplantation, kidney transplantation), except for the transplantation that does not require immunosuppressive therapy (such as: corneal transplantation, hair transplantation.)
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 |
|---|---|---|
| Anti-mesothelin CAR-T cellsD0: Anti-mesothelin CAR-T cells are autologous genetically modified T cells. Cells will be infused intravenously. | Biological | Anti-mesothelin CAR-T cells |
| FludarabineAlso: FludaraD-7 to D-3: Fludarabine (25 mg/m^2/day) will be administered intravenously for 5 days. | Drug | Anti-mesothelin CAR-T cells |
| CyclophosphamideAlso: CytoxanD-7 and D-6: Cyclophosphamide (60 mg/kg/day) will be administered intravenously for 2 days. | Drug | Anti-mesothelin CAR-T cells |
Primary outcome
TEAEs
Time frame: 4 weeks after the CAR-T cells infusion
Incidence and severity of treatment emergent adverse events.
TRAEs
Time frame: 4 weeks after the CAR-T cells infusion
Incidence and severity of treatment related adverse events.
AESIs
Time frame: 4 weeks after the CAR-T cells infusion
Incidence and severity of AEs of special interest.
2 secondary outcomes
Objective Response Rate (ORR) (PR+CR)
Time frame: 12 weeks
Duration of Overall Response（DOR）
Time frame: 24 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2023.
- Individual participant dataSharing planned: No
Related trials for Mesothelin-positive Advanced Refractory Solid Tumors
RecruitingPhase 1
CLDN6/GPC3/Mesothelin/AXL-CAR-NK Cell Therapy for Advanced Solid Tumors
Stage IV Ovarian Cancer, Testis Cancer, Refractory
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.
Zhiguo Long principal investigator
Shanghai Pudong Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Anti-mesothelin CAR-T cells, Fludarabine and Cyclophosphamide in people with Mesothelin-positive Advanced Refractory Solid Tumors, run by Shanghai Pudong Hospital at 1 site in China.
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 18 inclusion and 10 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: withdrawn, as of the sponsor's last update on 1 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
TEAEs (time frame: 4 weeks after the CAR-T cells infusion). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Mar 2023.