What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) include chemotherapy agents like gemcitabine, docetaxel, carboplatin, and paclitaxel, often combined with targeted therapies such as bevacizumab or immunotherapies like pembrolizumab and atezolizumab. The known side effects of these treatments can include neutropenia, febrile neutropenia, fatigue, nausea, increased liver function tests, hypertension, rash, stomatitis, and hemoptysis. Specific to immunotherapies, patients may experience immune-related adverse events such as pneumonitis, diarrhea, rash, and pruritus. These side effects vary in severity and frequency, and patients should discuss them with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

FDA-approved treatments for Non-Small Cell Lung Cancer (NSCLC) include a variety of chemotherapy and immunotherapy options. Chemotherapy agents such as docetaxel and gemcitabine have been approved for use in NSCLC, often in combination with other drugs. Immunotherapy agents like pembrolizumab and atezolizumab have also received FDA approval for NSCLC, particularly for patients without EGFR mutations or ALK translocations. These treatments aim to improve overall survival and progression-free survival in patients with advanced stages of the disease.

What other types of research exist?

Promising novel alternatives to ADI-PEG 20 for NSCLC patients include Furmonertinib, which has shown efficacy as a first-line therapy for EGFR mutation-positive NSCLC, and pembrolizumab, which has demonstrated prolonged overall survival in patients with PD-L1 expression of at least 1 percent. Additionally, durvalumab plus chemotherapy is an acceptable frontline option for metastatic NSCLC lacking EGFR or ALK mutations.

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Enzyme Depletion

ADI-PEG 20 + Chemotherapy for Lung Cancer

Phase 1 & 2

Recruiting

Led By Brian A Van Tine, M.D., Ph.D.

Research Sponsored by Washington University School of Medicine

Eligibility Criteria Checklist

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

Must have

Normal bone marrow and organ function as defined

Patients with NSCLC with a driver mutation (EGFR, ALK, ROS1) must have been treated with an FDA approved targeted therapy and subsequent platinum doublet therapy, if eligible

Must not have

Patients with known active Hepatitis B or C or HIV

Grade 2 or higher neuropathy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through the first 4 weeks of treatment for all phase i enrolled participants (estimated to be 12 months and 4 weeks)

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of three drugs to treat lung cancer patients who did not respond to initial treatments. The drugs work by starving the cancer cells and attacking them with chemotherapy.

Who is the study for?

Adults with small cell or non-small cell lung cancer that's worsened after initial treatment can join. They must have tried specific therapies based on their cancer type, be in good physical condition, and not be pregnant or breastfeeding. People with certain other cancers, active infections like Hepatitis B/C or HIV, severe neuropathy, untreated brain metastases, serious heart conditions, or a history of seizures unrelated to cancer are excluded.

What is being tested?

The trial is testing ADI-PEG 20 combined with chemotherapy drugs Gemcitabine and Docetaxel in patients whose lung cancer has progressed despite first-line therapy. The study starts by finding the safest dose combination (Phase I) before moving on to see how well it works at that dose (Phase II).

What are the potential side effects?

Possible side effects include reactions related to the immune system's response to ADI-PEG 20 and typical chemotherapy-related issues such as fatigue, nausea, hair loss, low blood counts leading to increased infection risk or bleeding problems.

Eligibility Criteria

Inclusion Criteria

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

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My bone marrow and organs are functioning normally.

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I have NSCLC with a specific mutation and have been treated with targeted and platinum-based therapies.

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My NSCLC lacks a driver mutation and I've had first-line therapy with platinum and anti-PD(L)1, if I was eligible.

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I am fully active and can carry on all pre-disease activities without restriction.

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I am 18 years old or older.

Exclusion Criteria

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

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I have active Hepatitis B, C, or HIV.

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I have moderate to severe nerve damage.

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I have previously been treated with ADI-PEG 20 or gemcitabine.

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I have brain metastases that haven't been treated or are unstable.

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I do not have any uncontrolled illnesses or heart problems.

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I have a history of seizures not caused by my cancer.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through the first 4 weeks of treatment for all phase i enrolled participants (estimated to be 12 months and 4 weeks)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through the first 4 weeks of treatment for all phase i enrolled participants (estimated to be 12 months and 4 weeks)

This trial's timeline: 3 weeks for screening, Varies for treatment, and through the first 4 weeks of treatment for all phase i enrolled participants (estimated to be 12 months and 4 weeks) for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Non-Small Cell Lung Carcinoma

Recommended phase II dose (Phase I only)

Therapeutic procedure

Secondary study objectives

Non-Small Cell Lung Carcinoma

Awards & Highlights

No Placebo-Only Group

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

Trial Design

3Treatment groups

Experimental Treatment

Group I: Phase II Small cell lung cancer: ADI-PEG + gemcitabine + docetaxelExperimental Treatment3 Interventions

* ADI-PEG 20 is given as an intramuscular injection on a weekly basis (Day 1, 8 and 15) at a dose of 36 mg/m\^2. ADI-PEG 20 dosing will start one week prior to the initiation of gemcitabine + docetaxel on Day -7 prior to the initiation of Cycle 1. * Gemcitabine is given intravenously at the assigned dose level on Day 2 of each cycle. * Docetaxel is given intravenously at the assigned dose level on Day 1 of each cycle. * A cycle is defined as 21 days. * After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) per physician discretion or patient request. * Treatment may continue for up to 34 cycles.

Group II: Phase II Non-small cell lung cancer: ADI-PEG + gemcitabine + docetaxelExperimental Treatment3 Interventions

Group III: Phase I: ADI-PEG + gemcitabine + docetaxelExperimental Treatment3 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

ADI-PEG 20

2013

Completed Phase 2

~190

Gemcitabine

2017

Completed Phase 3

~1920

Docetaxel

1995

Completed Phase 4

~6550

0 / 11Eligibility 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 Non-Small Cell Lung Cancer (NSCLC) include chemotherapy, immunotherapy, and targeted therapies. Chemotherapy drugs like gemcitabine and docetaxel work by interfering with the DNA replication process, thereby inhibiting cancer cell growth and inducing cell death. Immunotherapy, such as PD-1/PD-L1 inhibitors (e.g., nivolumab, pembrolizumab), enhances the immune system's ability to recognize and destroy cancer cells. Targeted therapies, including EGFR and ALK inhibitors, specifically target genetic mutations driving cancer growth. ADI-PEG 20, an arginine-depleting enzyme, starves cancer cells of arginine, an amino acid essential for their growth. Understanding these mechanisms is crucial for NSCLC patients as it helps tailor treatments to their specific cancer type, potentially improving efficacy and reducing side effects.

A Review of Recent Advances in the Treatment of Elderly and Poor Performance NSCLC.