What is the mechanism of action of this treatment?

Common treatments for colorectal cancer include surgery, chemotherapy, radiation therapy, and immunotherapy. Immunotherapy, particularly the use of autologous tumor infiltrating lymphocytes (TIL), involves extracting T-cells from a patient's tumor, expanding them in vitro, and reinfusing them to stimulate the immune system to target and destroy cancer cells. This approach leverages the body's own immune system to fight cancer, which can be particularly effective in cases of minimal residual disease. Understanding these mechanisms is crucial for colorectal cancer patients as it provides insight into how their treatment works, potential side effects, and the importance of personalized medicine in improving treatment outcomes.

What side effects are associated with this type of intervention?

Common treatments for colorectal cancer that involve immune system stimulation, such as immune checkpoint inhibitors, can lead to immune-related adverse events (irAEs). These include colitis, dermatitis, hepatitis, endocrinopathies like hypothyroidism, and pneumonitis. These side effects arise because the therapy activates the immune system, which may then target normal tissues as well as cancer cells.

What prior FDA approvals exist?

The FDA has approved several immunotherapies for the treatment of colorectal cancer, particularly for cases that are refractory or have specific genetic markers. Notably, pembrolizumab (Keytruda) and nivolumab (Opdivo) are immune checkpoint inhibitors that target PD-1 and have been approved for microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer. These treatments work by stimulating the immune system to recognize and attack cancer cells, similar to the approach being studied with autologous tumor infiltrating lymphocytes (MDA-TIL).

What other types of research exist?

Promising novel alternatives to Autologous Tumor Infiltrating Lymphocytes (MDA-TIL) for colorectal cancer patients include: 1) Immune checkpoint inhibitors such as pembrolizumab and dostarlimab, particularly for patients with dMMR or high TMB tumors. 2) PD-1/PD-L1 inhibitors like avelumab, which have shown efficacy in various cancers. 3) Combination therapies involving immune checkpoint inhibitors and other agents, such as lenvatinib plus pembrolizumab, which have demonstrated potential in other cancer types. Patients should discuss these options with their oncologist to determine the best course of action based on their specific medical condition.

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CAR T-cell Therapy

Tumor Infiltrating Lymphocytes for Ovarian Cancer

Phase 2

Waitlist Available

Led By Amir A Jazaeri

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

Ovarian cancer cohort only: Subjects must have failed at least two prior lines of chemotherapy

Pancreatic adenocarcinoma cohort only: Subjects must have progressed on, or received maximal benefit from, front-line therapy

Must not have

Active systemic infections requiring intravenous antibiotics, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system

Patients with active viral hepatitis

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 for patients with certain types of cancer that have returned or don't respond to usual treatments. The treatment uses the patient's own immune cells, grown in a lab, to help the body fight the cancer. The goal is to see if this approach can effectively control the cancer and improve patient outcomes.

Who is the study for?

This trial is for adults with recurrent or refractory ovarian, colorectal, or pancreatic ductal adenocarcinoma. Participants must have a tumor that can be biopsied and an ECOG performance status of 0-1. They should not have had recent treatments, HIV infection, significant heart/lung diseases, other cancers within 5 years, or certain chronic conditions. Women of childbearing potential must use effective birth control.

What is being tested?

The study tests autologous tumor infiltrating lymphocytes (MDA-TIL), which are T-cells grown from the patient's own tumor to boost the immune system against cancer cells. The process includes collecting T-cells from a biopsy and administering them back into the patient after chemotherapy with cyclophosphamide and fludarabine followed by interleukin-2 support.

What are the potential side effects?

Potential side effects include reactions related to immune stimulation such as fever and fatigue; complications from cell infusion; effects from chemotherapy like nausea and low blood counts; organ inflammation due to immune response; increased risk of infections; and possible heart stress due to interleukin-2.

Eligibility Criteria

Inclusion Criteria

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

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I have ovarian cancer and previous treatments with at least two types of chemotherapy did not work.

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My pancreatic cancer has not improved with initial treatment.

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I stopped all cancer treatments 28 days before my tumor removal surgery.

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My heart test before starting treatment was normal.

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My ovarian cancer is high grade and not mucinous.

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My colorectal cancer has spread and cannot be cured with current treatments.

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I have pancreatic cancer but do not have ascites or carcinomatosis.

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I do not have HIV.

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I have a tumor that can be partially removed for testing, separate from the main tumor being monitored.

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I have a confirmed diagnosis of pancreatic cancer with limited spread.

Exclusion Criteria

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

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I do not have any active infections needing IV antibiotics or major illnesses affecting my heart, lungs, or immune system.

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I have active viral hepatitis.

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I have a history of significant autoimmune disease.

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I have had cell therapy treatment before.

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I have a long-term lung condition like COPD or asthma.

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I am not allergic to any components of the TIL therapy or study drugs.

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I was diagnosed with another cancer type within the last 5 years.

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I have had an organ or bone marrow transplant.

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I have active brain metastases or cancer in the lining of my brain.

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My physical abilities have recently declined.

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

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Objective response rate (ORR)

Secondary study objectives

Complete response rate (CRR)

Disease control rate (DCR)

Duration of response (DOR)

+3 more

Other study objectives

Assessment of immunological phenotype of autologous tumor infiltrating lymphocytes MDA-TIL

Duration of tumor infiltrating lymphocyte (TIL) persistence

Health-related quality of life

+2 more

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: Treatment (autologous tumor infiltrating lymphocytes MDA-TIL)Experimental Treatment5 Interventions

LYMPHODEPLETION REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days -7 and -6, and fludarabine IV over 15-30 minutes on days -5 to -1 in the absence of disease progression or unacceptable toxicity. T-CELL INFUSION: Patients receive autologous tumor infiltrating lymphocytes MDA-TIL IV over 45 minutes on day 0. Patients then receive IL-2 IV over 30 minutes on days 1-4 for up to 6 doses in the absence of disease progression or unacceptable toxicity.

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

Interleukin-2

1994

Completed Phase 3

~840

0 / 20Eligibility 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 colorectal cancer include surgery, chemotherapy, radiation therapy, and immunotherapy. Immunotherapy, particularly the use of autologous tumor infiltrating lymphocytes (TIL), involves extracting T-cells from a patient's tumor, expanding them in vitro, and reinfusing them to stimulate the immune system to target and destroy cancer cells. This approach leverages the body's own immune system to fight cancer, which can be particularly effective in cases of minimal residual disease. Understanding these mechanisms is crucial for colorectal cancer patients as it provides insight into how their treatment works, potential side effects, and the importance of personalized medicine in improving treatment outcomes.

Active specific immunotherapy with autologous tumor cell vaccines for stage II colon cancer: logistics, efficacy, safety and immunological Pharmacodynamics.