What side effects are associated with this type of intervention?

The most common treatments for adenocarcinoma, including genetically modified NK cell therapies like TROP2-CAR-NK, can cause a variety of side effects. These may include cytokine release syndrome (CRS), which can lead to fever, fatigue, and muscle pain. Other potential side effects are neurotoxicity, resulting in headaches, confusion, or seizures, and hematologic toxicities such as anemia, thrombocytopenia, and neutropenia. Additionally, patients may experience gastrointestinal symptoms like nausea, vomiting, and diarrhea. It is important to monitor and manage these side effects under the guidance of a healthcare professional.

What prior FDA approvals exist?

As of now, there are no specific FDA approvals for genetically modified NK cells targeting TROP2 in the treatment of adenocarcinoma. However, the FDA has approved several CAR-T cell therapies for other types of cancers, such as Kymriah (tisagenlecleucel) and Yescarta (axicabtagene ciloleucel) for certain types of lymphomas and leukemias. For adenocarcinoma, treatment typically involves a combination of surgery, chemotherapy, and targeted therapies, such as trastuzumab for HER2-positive gastric adenocarcinoma. The investigational TROP2-CAR-NK therapy represents a novel approach that is still under clinical investigation.

What other types of research exist?

Promising novel alternatives to TROP2-CAR-NK for adenocarcinoma patients include: 1) Immune checkpoint inhibitors such as anti-PD-1 or anti-PD-L1 therapies, which have shown efficacy in various cancers including lung and melanoma. 2) Combination therapies involving checkpoint inhibitors and other agents, such as lenvatinib plus pembrolizumab, which have demonstrated clinical activity in immunotherapy-refractory cancers. 3) Targeted therapies for specific genetic mutations, such as larotrectinib or entrectinib for NTRK fusion-positive tumors, and sotorasib or adagrasib for KRAS G12C mutations. These alternatives offer potential benefits and should be discussed with a healthcare provider to determine the best personalized treatment approach.

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CAR T-cell Therapy

TROP2-CAR-NK Cells for Platinum-Resistant Ovarian Cancer

Phase 1 & 2

Recruiting

Led By Amir Jazaeri, MD

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

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

Must have

A histology confirming diagnosis of mesonephric-like adenocarcinoma (MLA) originating from the female reproductive tract or peritoneal lining (including MLA arising from endometriosis) with pathology reviewed at MD Anderson Cancer Center

Subjects must have failed at least one prior line of platinum-containing chemotherapy

Must not have

Has received systemic anti-cancer therapy including investigational agents within 4 weeks of starting lymphodepleting chemotherapy

Radiographic evidence of tumor encasement or invasion of a major blood vessel, or intra-tumoral cavitation

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new treatment where specially modified immune cells are injected into the abdomen of patients with advanced ovarian cancer that hasn't responded to other treatments. These immune cells are designed to find and destroy cancer cells by recognizing a specific marker on them. This approach has shown promise in treating ovarian cancer.

Who is the study for?

This trial is for adults with certain types of cancer (high-grade serous ovarian, mesonephric-like adenocarcinoma, or pancreatic) that are resistant to standard treatments. Participants must have an ECOG performance status of 0 or 1, agree to contraception if applicable, and have adequate organ function. They should not be pregnant/breastfeeding and must have failed previous chemotherapy lines.

What is being tested?

The study tests TROP2-CAR-NK cells delivered into the abdomen combined with Cyclophosphamide and Fludarabine in patients with specific cancers. It aims to find the optimal dose for those whose cancer hasn't responded well to other treatments.

What are the potential side effects?

Potential side effects may include reactions at the infusion site, immune system complications due to CAR-NK cells, as well as typical chemotherapy-related issues like nausea, fatigue, low blood counts leading to increased infection risk.

Eligibility Criteria

Inclusion Criteria

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

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My cancer, originating from the female reproductive tract or peritoneal lining, has been confirmed as mesonephric-like adenocarcinoma by MD Anderson Cancer Center.

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I have had platinum-based chemotherapy before and it did not work.

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My cancer can be measured and is present in my abdomen or lymph nodes near my spine.

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

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My cancer did not respond to at least two chemotherapy treatments or is resistant to platinum-based treatment.

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My cancer progressed after initial treatment with FOLFIRINOX or gemcitabine.

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My tumor shows some level of TROP2 protein.

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I am 18 years old or older.

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I am willing to have a port placed in my abdomen for treatment and to have fluid and blood samples taken regularly.

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My cancer is high grade serous ovarian, peritoneal, or fallopian tube, confirmed by MD Anderson.

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I have a BRCA mutation and have been treated with PARP inhibitors before.

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I have been diagnosed with pancreatic or ampullary-type cancer.

Exclusion Criteria

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

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I have not had any cancer treatment or experimental drugs in the last 4 weeks.

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My tumor is affecting a major blood vessel or has cavities inside it.

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I am currently on medication for an infection.

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I have a history of chronic Hepatitis B or C.

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I currently have an infection in my abdomen.

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I have had lung conditions that needed steroids or currently have lung inflammation.

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I have an active tuberculosis infection.

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I had another cancer but was treated successfully with no signs of cancer for 2 years, or I had certain skin, bladder, cervical, or in-situ cancers treated successfully.

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I have an immune system disorder or have been on high-dose steroids or other immune-weakening medicines recently.

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I have received an organ or tissue transplant from another person.

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

1Treatment groups

Experimental Treatment

Group I: TROP2-CAR-NKExperimental Treatment3 Interventions

Participants will receive 1 dose of TROP2-CAR-NK and will visit the study clinic up to 16 times to have tests and procedures (such as blood draws, biopsies, and CT scans). Participants will receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine) for 3 days in a row. Participants will receive cyclophosphamide and fludarabine by vein over about 3 hours total.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cyclophosphamide

2010

Completed Phase 4

~2310

Fludarabine

2012

Completed Phase 4

~1860

0 / 22Eligibility 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

The most common treatments for adenocarcinoma include targeted therapies and immunotherapies. Targeted therapies, such as kinase inhibitors, work by blocking specific molecules involved in cancer cell growth and survival, thereby inhibiting tumor progression. Immunotherapies, including CAR-NK cell therapies like TROP2-CAR-NK, enhance the body's immune response against cancer cells. These genetically modified NK cells are designed to recognize and kill cancer cells expressing the TROP2 protein. This approach is significant for adenocarcinoma patients as it offers a more personalized treatment option, potentially leading to better outcomes by specifically targeting cancer cells while sparing normal tissues.

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