Malignant Peritoneal EffusionPhase 1NCT05477927
Dual-targeting VEGFR1 and PD-L1 CAR-T for Pleural, Peritoneal, or Leptomeningeal Metastases
A Phase 1 study testing Dual-targeting VEGFR1/PD-L1 CAR-T cells in people with Malignant Peritoneal Effusion and Malignant Ascites, run by Sichuan University at 1 site in China.
Trial summary
This is a Phase I, open-label, single-arm, dose-escalation and expansion study designed to evaluate the safety, tolerability, and preliminary antitumor activity of dual-targeting VEGFR1/PD-L1 chimeric antigen receptor (CAR) T-cells in patients with solid tumors presenting with pleural, peritoneal, or leptomeningeal… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Malignant Peritoneal Effusion, Malignant Ascites, Serous Cavity Metastatises
- What is being tested?
- Dual-targeting VEGFR1/PD-L1 CAR-T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- 15 Feb 2023to 31 Dec 2028
- Phase
- Phase 1
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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female participants aged 18 to 75 years. Participants older than 75 years may be enrolled at the investigator's discretion based on overall health status.
- Females of childbearing potential must have a negative serum or urine pregnancy test. Females who have undergone surgical sterilization or have been postmenopausal for at least 2 years are considered not of childbearing potential.
- Histologically or cytologically confirmed advanced solid tumors with evidence of serosal cavity metastasis (pleural/peritoneal) and/or leptomeningeal metastasis, who have failed standard-of-care therapies.For leptomeningeal metastasis: patients must have received at least 3 intrathecal chemotherapy infusions with persistent positive CSF cytology and neurological symptoms, OR have re-positivity of CSF cytology after prior clearance.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Life expectancy > 3 months.
- Adequate organ and bone marrow function:
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- Absolute neutrophil count ≥ 1.5 × 10⁹/L Platelets ≥ 90 × 10⁹/L Absolute lymphocyte count ≥ 1.0 × 10⁸/L Hemoglobin ≥ 9.0 g/dL ALT/AST ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver metastases) Total bilirubin ≤ 1.5 × ULN Creatinine < 1.5 × ULN AND creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula). Creatinine clearance assessment is required only when creatinine ≥ 1.5 × ULN.
- Cardiac ejection fraction ≥ 50%. Patients with minimal or moderate pericardial effusion may be enrolled at the investigator's discretion.
- No other severe concurrent diseases (e.g., active autoimmune diseases, immunodeficiency).
- Chemotherapy must be discontinued for at least 3 weeks prior to CAR-T cell infusion.
- Sexually active participants of childbearing potential must agree to use highly effective contraceptive methods from screening through 1 year after CAR-T cell infusion.
- Voluntary participation with written informed consent obtained prior to any study-specific procedures.
- Recovery from prior antitumor therapy to ≤ Grade 1 (CTCAE v5.0), except for alopecia, hormone-replacement-controlled hypothyroidism, Grade 2 peripheral neuropathy, vitiligo, well-controlled diabetes, or other chronic toxicities deemed by the investigator to be stable and not interfering with study conduct.
Who cannot join
- Known hypersensitivity to cytokines.
- Active infection requiring systemic anti-infective therapy.
- Acute or chronic graft-versus-host disease (GVHD).
- History of malignancies other than the target indication within 5 years prior to screening, with the exception of adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast after curative resection.
- Active hepatitis B or C, or HIV infection. HBsAg-positive patients may be enrolled if HBV DNA is below the lower limit of normal (LLN) per institutional standard; HCV antibody-positive patients may be enrolled if HCV RNA is below LLN per institutional standard. Carriers require antiviral therapy as clinically indicated and periodic quantitative nucleic acid testing during the study.
- Prior immunotherapy-related adverse event of Grade ≥ 3, or any other concurrent disease, metabolic dysfunction, physical examination finding, or laboratory abnormality that would reasonably preclude use of the investigational product, confound study results, or place the participant at undue risk.
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- Clinically significant cardiovascular disease, including but not limited to:Congestive heart failure (NYHA Class > 2);Unstable angina;Myocardial infarction within the past 3 months;Supraventricular or ventricular arrhythmia requiring treatment or intervention;Poorly controlled Grade 2-3 hypertension
- Known psychiatric disorders, alcoholism, drug abuse, or substance dependence that may interfere with study compliance.
- Active autoimmune disease, history of autoimmune disease, or condition requiring systemic corticosteroids (> 10 mg/day prednisone or equivalent) or immunosuppressive therapy (e.g., post-organ transplantation). Inhaled corticosteroids are permitted.
- Unstable pulmonary embolism, deep vein thrombosis, or other major arterial/venous thromboembolic events within 6 months prior to enrollment. Patients on anticoagulation therapy must be on a stable dose prior to enrollment.
- Pregnant or lactating women, or women planning pregnancy during the treatment period or within 1 year after CAR-T cell infusion.Women of childbearing potential unwilling to use highly effective contraception during the treatment period and for 1 year after CAR-T cell infusion. A negative serum or urine pregnancy test (within 48 hours prior to treatment) is required for women of childbearing potential.
- Any condition that, in the investigator's opinion, precludes the participant from providing written informed consent or complying with study procedures.
- Any other condition deemed by the investigator as inappropriate for study participation.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
West China Hospital, Sichuan University
Chengdu, Sichuan, 610041
XIA HE, PhD., (+86)18583365730, 18583365730@163.com
DAN LI, PhD., (+86)13880025826, lidan@wchscu.cn
About this study
Official title: A Phase I, Open-label, Single-arm, Dose-escalation and Expansion Study of Dual-targeting VEGFR1 and PD-L1 CAR-T Cells in Patients With Pleural, Peritoneal, or Leptomeningeal Metastases From Solid Tumors
This is a Phase I, open-label, single-arm, dose-escalation and expansion study designed to evaluate the safety, tolerability, and preliminary antitumor activity of dual-targeting VEGFR1/PD-L1 chimeric antigen receptor (CAR) T-cells in patients with solid tumors presenting with pleural, peritoneal, or leptomeningeal metastases.
Despite advances in systemic therapies, patients with serosal cavity and leptomeningeal dissemination face extremely poor prognoses and limited treatment options due to the unique immunosuppressive tumor microenvironment and the physical barrier of these anatomical sites. Preclinical evidence suggests that simultaneous blockade of VEGFR1-mediated angiogenesis and PD-L1-mediated immune checkpoint signaling via a bispecific CAR-T construct may synergistically overcome local immunosuppression and enhance tumor eradication in these sanctuary sites.
Read more
The study consists of two phases: a dose-escalation phase utilizing a standard 3+3 design and backfilling design to determine the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of locoregionally administered CAR-T cells, followed by a dose-expansion phase to further assess safety and preliminary efficacy at the RP2D.
Eligible patients will receive a single infusion of VEGFR1/PD-L1 dual-CAR T-cells via intrapleural, intraperitoneal, or intrathecal routes, depending on the primary site of metastasis. The primary endpoints are the incidence of dose-limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs) graded by CTCAE v5.0. Secondary endpoints include objective response rate (ORR) , progression-free survival (PFS), overall survival (OS), and assessment of CAR-T cell persistence and cytokine profiles in peripheral blood and local effusion fluids.
Read the detailed description
The study comprises two independent cohorts based on metastatic site and route of administration:
Cohort 1 - Pleural or Peritoneal Metastases (Intracavitary Administration):
This cohort enrolls patients with solid tumors who have developed pleural or peritoneal metastases and have failed standard-of-care therapies. A standard 3+3 dose-escalation design is applied with three dose levels: 2×10⁶, 5.0×10⁶, and 1.0×10⁷ CAR-T cells/kg. Cells are administered via intrapleural or intraperitoneal injection based on the predominant metastatic site.
Cohort 2 - Leptomeningeal Metastases (Intrathecal Administration):
This cohort enrolls patients with cytologically or radiologically confirmed leptomeningeal metastases from solid tumors who have failed prior standard therapies. A dose-escalation with backfill cohort strategy is employed, with three prespecified dose levels (DL): DL1 at 7.5×10⁶ CAR-T cells, DL2 at 1.5×10⁷ CAR-T cells, and DL3 at 3.0×10⁷ CAR-T cells, all administered via intrathecal injection. The escalation method differs by dose level: DL1 follows an accelerated titration design (single participant), while DL2 and DL3 follow the standard 3+3 design. Backfill cohorts will be initiated only after the DL2 main cohort has completed the DLT observation period and the DL3 main cohort has enrolled 3 participants who have entered the DLT window. Thereafter, newly enrolled patients will be randomly allocated (for dose assignment only) to either the DL2 or DL3 backfill cohorts, with 3 additional participants per level. The final recommended phase II dose (RP2D) for leptomeningeal metastases will be comprehensively determined using pooled safety and tolerability data from both the main escalation and backfill cohorts.
The dose-limiting toxicity (DLT) observation period is 21 days post-first infusion for both cohorts. Adverse events are graded per NCI-CTCAE v5.0. Following RP2D determination for each cohort, a dose-expansion phase will be initiated to further evaluate safety and preliminary efficacy in a larger patient population.
- Conditions
- Malignant Peritoneal Effusion, Malignant Ascites, Serous Cavity Metastatises, Leptomeningeal Metastases
- Being tested
- Dual-targeting VEGFR1/PD-L1 CAR-T cells
- Keywords
- CAR-T regional injection, Solid Tumors, Serosal Cavity metastases, leptomeningeal metastases
- Medical subject headings
- Meningeal Carcinomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dual-targeting VEGFR1/PD-L1 CAR-T cellsBiological
Autologous T cells genetically engineered to express a chimeric antigen receptor targeting both VEGFR1 and PD-L1. Cells are administered via locoregional routes.
| Study group | Role | What they receive |
|---|---|---|
| VEGFR1/PD-L1 Dual-Targeting CAR-T Cell Therapy | Experimental | Participants receive a single infusion of autologous VEGFR1/PD-L1 dual-targeting chimeric antigen receptor (CAR) T-cells via locoregional administration (intrapleural, intraperitoneal, or intrathecal) depending on the metastatic site. The dose is escalated according to the assigned cohort's protocol. Receives: Biological: Dual-targeting VEGFR1/PD-L1 CAR-T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
AEs and SAEs
Safety
Measured: 6 months after infusion
Dose-limiting toxicity (DLT)
Tolerability evaluation
Measured: 21 days
Recommended phase II dose (RP2D).
Efficacy dose
Measured: Approximately 2 years.
Secondary outcomes (9)
Objective Remission Rate (ORR).
Measured: From date of first CAR-T cell infusion until the date of first documented disease progression or death,up to 5 years.
Progression-Free Survival (PFS ).
Measured: From date of first CAR-T cell infusion until the date of first documented disease progression or death，assessed up to 5 years.
Duration Of Control Rate (DCR).
Measured: From date of first CAR-T cell infusion until the date of first documented disease progression or death，assessed up to 5 years.
Duration Of Response (DOR).
Measured: From date of first CAR-T cell infusion until the date of first documented disease progression or death，assessed up to 5 years.
Overall-Survival (OS).
Measured: From date of CAR-T cell infusion until date of death from any cause, assessed up to 5 years
CSF Tumor Cell Clearance Rate
Proportion of participants with conversion from positive to negative CSF cytology/flow cytometry
Measured: Up to 5 years
Duration of CSF Clearance
Time from first CSF clearance to CSF re-positivity or death
Measured: Up to 5 years
Neurological Symptom and Intracranial Pressure Improvement Rate
Composite of ≥1-grade neurological symptom improvement and ≥20% reduction in CSF opening pressure from baseline, assessed concurrently
Measured: Up to 5 years
CAR-T cell numbers.
PK/PD
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 posted28 Jul 2022
- Study start15 Feb 2023
- Primary completion30 Jun 2027 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Malignant Peritoneal EffusionStudies 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
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sichuan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yongsheng Wang, West China Hospital
- Investigators
- Yongsheng Wang, Prof., Principal investigator, West China Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05477927
- Sponsor's protocol ID
- MCART-006
- Status last verified
- Aug 2026
- First submitted
- 7 May 2022
- Last updated
- 13 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Cheema PK, Burkes RL. Overall survival should be the primary endpoint in clinical trials for advanced non-small-cell lung cancer. Curr Oncol. 2013 Apr;20(2):e150-60. doi: 10.3747/co.20.1226.
PubMed 23559882Wagner DL, Fritsche E, Pulsipher MA, Ahmed N, Hamieh M, Hegde M, Ruella M, Savoldo B, Shah NN, Turtle CJ, Wayne AS, Abou-El-Enein M. Immunogenicity of CAR T cells in cancer therapy. Nat Rev Clin Oncol. 2021 Jun;18(6):379-393. doi: 10.1038/s41571-021-00476-2. Epub 2021 Feb 25.
PubMed 33633361