What side effects are associated with this type of intervention?

Common treatments for ovarian cancer, such as chemotherapy with paclitaxel and cisplatin, often result in side effects including nausea, vomiting, hair loss, fatigue, and hematologic toxicities like neutropenia and thrombocytopenia. Additionally, CAR T-cell therapies, which are being explored in trials for mesothelin-expressing cancers, can cause cytokine release syndrome (CRS), neurotoxicity, and other immune-related adverse events. These side effects are generally manageable but require close monitoring and supportive care.

What prior FDA approvals exist?

FDA-approved treatments for ovarian cancer include a variety of chemotherapies, targeted therapies, and immunotherapies. Notable targeted therapies include PARP inhibitors like olaparib, niraparib, and rucaparib, which are used for patients with BRCA mutations or homologous recombination deficiencies. Bevacizumab, an anti-angiogenic agent, is also approved for use in combination with chemotherapy. While CAR T-cell therapies, such as lentiviral transduced huCART-meso cells targeting mesothelin, are being studied in clinical trials, they have not yet received FDA approval for ovarian cancer treatment.

What other types of research exist?

Promising novel alternatives for ovarian cancer treatment in 2024 include: 1) PI3K/PTEN/AKT/mTOR pathway inhibitors such as temsirolimus, which has shown some promise in clinical trials; 2) Monoclonal antibodies targeting PD-1/PD-L1, like pembrolizumab, which have demonstrated efficacy in various cancers; 3) Combination therapies involving mTOR inhibitors and other agents, such as everolimus with letrozole, which have shown clinical benefit in trials. These alternatives are under investigation and may offer new hope for ovarian cancer patients.

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CAR T-cell Therapy

CAR T Cell Therapy for Mesothelioma

Phase 1

Waitlist Available

Led By Janos L Tanyi, MD, PhD

Research Sponsored by University of Pennsylvania

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subjects with asymptomatic CNS metastases that have been treated and meet specific criteria

Subjects must be ≥ 18 years of age with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Must not have

Clinically significant pericardial effusion or cardiovascular conditions

Active invasive cancer other than the specified cancers in the study

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests the safety of using modified immune cells to treat cancer. These cells are given through an IV or directly into the body and are designed to find and kill cancer cells. The study focuses on cancer patients who may not respond well to traditional treatments.

Who is the study for?

Adults over 18 with certain advanced cancers (like lung adenocarcinoma, ovarian cancer) who've had at least one chemo treatment can join. They must be fairly active and healthy otherwise, not have serious heart or lung conditions, no HIV/Hepatitis B/C, and agree to birth control. Those with treated brain metastases meeting specific criteria may also qualify.

What is being tested?

The trial is testing huCART-meso cells in patients with mesothelin expressing cancers. It's a Phase I study looking at the safety of these cells given through IV or directly into the tumor area, with some patients possibly having their immune systems temporarily weakened first.

What are the potential side effects?

Possible side effects include reactions related to the immune system attacking normal tissues (autoimmune-like), infusion reactions from the cell therapy itself, and typical risks associated with weakening of the immune system if lymphodepletion is part of treatment.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My brain metastases have been treated and are not causing symptoms.

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I am 18 or older and can care for myself with minimal assistance.

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My cancer is confirmed and includes specific types like lung or ovarian cancer.

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My cancer can be measured by specific medical criteria.

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My organ and bone marrow functions are within normal ranges.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have serious heart fluid buildup or heart conditions.

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I do not have any active cancer other than the one specified in the study.

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I have cancer spread to the lining of my brain or spinal cord.

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I have brain metastases causing symptoms.

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I currently have an infection.

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I need extra oxygen to help me breathe.

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I have had treatment with gene-modified cells before.

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I rely on steroids or immunosuppressant drugs.

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I have fluid buildup that can't be drained with usual methods.

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My mesothelioma is either sarcomatoid or biphasic.

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I am HIV positive.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

7Treatment groups

Active Control

Group I: Cohort 7Active Control1 Intervention

Cyclophosphamide 300 mg/m\^2/day and fludarabine 30 mg/m\^2/day given over 3 days by IV infusion followed by a single dose of 1-3x10\^7 huCART-meso cells/m\^2 via intraperitoneal (i.p.) administration. Lymphodepleting chemotherapy will be scheduled such that the last day of chemotherapy is 3 days (+/- 1 day) prior to the infusion of huCART-meso cells. This initial i.p. infusion may be followed by up to two additional infusions of huCART-meso cells via intravenous (IV) administration at the same dose level, given between 21-42 days apart. The subject must meet eligibility to receive additional infusions. Lymphodepleting chemotherapy will not be repeated prior to additional infusions of huCART-meso cells.

Group II: Cohort 4Active Control1 Intervention

PERMANENTLY CLOSED

Group III: Cohort 1Active Control1 Intervention

Single dose of 1-3x10\^7 huCARTmeso cells/m\^2

Group IV: Cohort 3Active Control1 Intervention

PERMANENTLY CLOSED

Group V: Cohort 2Active Control1 Intervention

Cyclophosphamide 1 gram/m\^2 administered 2-4 days prior to a single dose of 1-3x10\^7 huCARTmeso cells/m\^2

Group VI: Cohort 5Active Control1 Intervention

Single dose of 1-3x10\^7 huCART-meso cells/m\^2 day 0 by intrapleural infusion (IP) through an indwelling pleural catheter without any conditioning chemotherapeutic regimen.

Group VII: Cohort 6Active Control1 Intervention

Cyclophosphamide 1 gram/m\^2 administered 2-4 days prior to dose of 1-3x10\^7 huCART-meso cells/m\^2 via IV infusion on Day 0. This initial infusion may be followed by up to two additional IV infusions of huCART-meso cells at the same dose level, given approximately 21-42 days apart, if the subject meets eligibility to receive additional infusions. Cyclophosphamide will not be repeated prior to subsequent doses of huCART-meso cells.

0 / 16Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for ovarian cancer include chemotherapy, targeted therapy, and immunotherapy. Chemotherapy, such as carboplatin and paclitaxel, works by damaging the DNA of rapidly dividing cancer cells, leading to cell death. Targeted therapies, like PARP inhibitors, interfere with specific molecules involved in cancer cell growth and survival. Immunotherapy, including checkpoint inhibitors, enhances the immune system's ability to recognize and destroy cancer cells. The trial involving Lentiviral Transduced huCART-meso Cells represents a form of immunotherapy where T cells are genetically engineered to target mesothelin, a protein commonly overexpressed in ovarian cancer cells. This approach aims to improve the precision and effectiveness of the immune response against cancer cells, offering hope for better outcomes in ovarian cancer patients.