What side effects are associated with this type of intervention?

Common treatments for pancreatic cancer, such as chemotherapy with agents like gemcitabine and nab-paclitaxel, often result in side effects including neutropenia, fatigue, neuropathy, and gastrointestinal issues like diarrhea. For treatments involving genetically modified T cells and oncolytic viruses, potential side effects may include cytokine release syndrome, infusion reactions, and on-target, off-tumor effects, which can lead to damage in healthy tissues. Additionally, oncolytic virus therapies may cause flu-like symptoms, inflammation, and potential viral shedding.

What prior FDA approvals exist?

The FDA has approved several treatments for pancreatic cancer, primarily focusing on chemotherapy and targeted therapies. Notable approvals include gemcitabine, often used in combination with other agents like nab-paclitaxel, and fluoropyrimidines such as capecitabine. While there is ongoing research into advanced therapies like genetically modified T cells and oncolytic viruses, specific FDA approvals for treatments directly analogous to huCART-meso cells and VCN-01 are not detailed in the provided context. However, the field is evolving with promising clinical trials exploring these innovative approaches.

What other types of research exist?

Promising novel alternatives for pancreatic cancer treatment include: 1) PF-07062119, an anti-GUCY2C/anti-CD3ε bispecific construct that targets GUCY2C-positive tumors and has shown potent T-cell-mediated activity and efficacy in colorectal cancer models, which may be applicable to pancreatic cancer. 2) Purified VP22-EGFP fusion protein, which offers a peptide-mediated and potentially systemic therapy for pancreatic cancer by enhancing apoptosis. 3) Novel antibodies to cancer testis antigen Centrin-1 (CETN1) for radioimmunotherapy, which have demonstrated specific binding to pancreatic cancer cells and effective tumor localization and treatment in preclinical models.

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CAR T-cell Therapy

huCART-meso + VCN-01 for Pancreatic Cancer

Phase 1

Recruiting

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

Patients with histologically confirmed unresectable or metastatic pancreatic adenocarcinoma

Patients who have progressed or shown intolerance to at least one prior standard of care chemotherapy for advanced stage disease

Must not have

Patients with any clinically significant pericardial effusion, Class II-IV cardiovascular disability, or other cardiovascular condition that would preclude assessment of mesothelin induced pericarditis

Patients with chronic hepatitis C with a FibroScan score equivalent to fibrosis stage 2 (F2) or greater

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of modified immune cells and a virus-based therapy in patients who may not have responded to other treatments. The immune cells are designed to target and destroy cancer cells, while the virus helps by killing cancer cells and enhancing the immune response. The virus therapy has been approved for the treatment of metastatic melanoma.

Who is the study for?

This trial is for adults with specific advanced cancers: unresectable or metastatic pancreatic adenocarcinoma, and persistent or recurrent serous epithelial ovarian cancer. Participants must have tried at least one standard chemotherapy, be in good physical condition (ECOG 0-1), not need oxygen therapy, and have no other active invasive cancers or significant health issues like heart disease, autoimmune diseases requiring steroids, or certain infections.

What is being tested?

The study tests a combination of huCART-meso cells and VCN-01 on patients with ovarian and pancreatic cancer using a '3+3 dose escalation' method to find the safest dose. This means small groups of patients receive increasing doses until doctors determine the highest dose that can be given safely.

What are the potential side effects?

While specific side effects are not listed here, Phase I trials like this focus on safety and will monitor for any adverse reactions to the treatment combination. Side effects could range from mild reactions at injection sites to more serious immune responses.

Eligibility Criteria

Inclusion Criteria

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

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My pancreatic cancer cannot be removed by surgery and has spread.

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My condition worsened or I couldn't tolerate the treatment after one standard chemotherapy.

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My ovarian cancer is serous type and has come back or not gone away.

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I am 18 years old or older.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I have minor breathing issues and my oxygen level is above 92% without assistance.

Exclusion Criteria

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

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I do not have serious heart fluid buildup or heart conditions that could affect the study.

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I have chronic hepatitis C with moderate to severe liver scarring.

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I am scheduled to receive high dose corticosteroids along with my treatment.

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I do not have any active cancer other than the one this study is targeting.

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My cancer has spread to my brain.

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I currently have an infection.

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I have an active hepatitis B or C infection.

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I have a history of Li Fraumeni syndrome or a genetic issue related to retinoblastoma.

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I have not taken PD-1 or PD-L1 inhibitors in the last 2 months.

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I have been diagnosed with cirrhosis.

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I am on strong medication for an autoimmune disease, similar to 10 mg of prednisone or more.

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I need extra oxygen.

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

3Treatment groups

Active Control

Group I: Cohort 2Active Control2 Interventions

Single dose of 1x10(13) vp of VCN-01 on Day 0, followed by a single dose of 5x10(7) of huCART-meso cells on Day 14.

Group II: Cohort -1Active Control2 Interventions

In the event that 2 DLTs occur in Cohort 1, then enrollment in Cohort 1 will be stopped and Cohort -1 will be opened for evaluation. Enrolled subjects will receive a single dose of huCART-meso cells on Day 0 followed by a single dose of 3.3x10(12) vp of VCN-01 on Day 14.

Group III: Cohort 1Active Control2 Interventions

Single dose of 3.3x10(12) vp of VCN-01 on Day 0, followed by a single dose of 5x10(7) of huCART-meso cells on Day 14.

0 / 18Eligibility 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 pancreatic cancer include chemotherapy, targeted therapy, and immunotherapy. Chemotherapy, such as FOLFIRINOX, works by damaging the DNA of rapidly dividing cancer cells, leading to cell death. Targeted therapies, like PARP inhibitors for patients with BRCA mutations, specifically inhibit proteins involved in DNA repair, making cancer cells more susceptible to damage. Immunotherapy, including chimeric antigen receptor (CAR) T cells, involves genetically modifying a patient's T cells to target and kill cancer cells. Oncolytic viruses, such as adenoviruses, selectively infect and kill cancer cells while stimulating an anti-tumor immune response. These mechanisms are crucial for pancreatic cancer patients as they offer more precise and potentially effective treatment options, especially for those with advanced or treatment-resistant disease.