What side effects are associated with this type of intervention?

Common treatments for lung carcinoma, particularly those involving EGFR inhibitors like Osimertinib, often result in side effects such as rash, diarrhea, and interstitial lung disease. Osimertinib specifically can cause skin issues, gastrointestinal disturbances, and potentially serious lung conditions. Other targeted therapies and chemotherapeutic agents used in lung cancer treatment may lead to a range of side effects including nausea, vomiting, fatigue, hematologic toxicities (like neutropenia and anemia), and neuropathy. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of lung carcinoma, particularly targeting EGFR mutations. Osimertinib, an EGFR inhibitor, is one such drug that has shown efficacy in treating non-small cell lung cancer (NSCLC) with EGFR mutations. Other EGFR inhibitors that have received FDA approval include erlotinib and gefitinib. These drugs work by blocking the activity of the EGFR protein, which is often overexpressed in certain types of lung cancer, leading to uncontrolled cell growth. While Minnelide is still under investigation, its active compound triptolide has anti-cancer properties that are being explored in combination with EGFR inhibitors like Osimertinib to enhance treatment efficacy.

What other types of research exist?

Promising novel alternatives for lung carcinoma patients in 2024 include: <ol> <li>Tepotinib - A MET inhibitor showing a 46% overall response rate in NSCLC with MET exon-14-skipping mutations.</li> <li></li> </ol> Capmatinib - Another MET inhibitor approved for MET-dysregulated NSCLC. 3. Larotrectinib and Entrectinib - TRK inhibitors effective in tumors with NTRK gene fusions. 4. Selpercatinib and Pralsetinib - RET inhibitors for RET-mutated lung cancers. These alternatives target specific genetic mutations and pathways, offering personalized treatment options.

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Triptolide Analog

Minnelide + Osimertinib for Lung Cancer

Q: What is the mechanism of action of this treatment?

Minnelide, a prodrug that converts to the active compound triptolide, inhibits cancer cell proliferation by disrupting transcription and protein degradation processes. Osimertinib, an EGFR inhibitor, blocks the epidermal growth factor receptor, which is frequently mutated in lung cancer, leading to uncontrolled cell growth. These targeted therapies are significant for lung carcinoma patients as they offer more precise treatment options that can effectively inhibit tumor growth and potentially improve survival rates.

Phase 1

Recruiting

Led By Erminia Massarelli

Research Sponsored by City of Hope Medical Center

Eligibility Criteria Checklist

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

Must have

The tumor harbors 1 of the 2 common epidermal growth factor receptor (EGFR) mutations known to be associated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) sensitivity (Ex19del or L858R), either alone or in combination with other epidermal growth factor receptor (EGFR) mutations, which may include T790M

If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) =< 1.5 x ULN (within 14 days prior to day 1 of protocol therapy)

Must not have

Active diarrhea

Diagnosis of congenital long QT syndrome

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

Summary

This trial tests Minnelide and Osimertinib together to treat advanced lung cancer with a specific gene mutation. Minnelide becomes an active drug in the body, and Osimertinib blocks a protein needed for cancer growth. This combination aims to help patients whose cancer grows faster due to this specific gene mutation. Osimertinib is a third-generation medication approved for treating a type of lung cancer with specific gene mutations.

Who is the study for?

Adults with advanced non-small cell lung cancer that has spread and have specific EGFR gene mutations. They must have had tumor progression after standard osimertinib treatment, be able to swallow pills, not be pregnant or breastfeeding, use effective birth control, and agree to research biopsies. Excluded are those with certain heart conditions, active infections requiring systemic therapy, recent use of strong CYP3A4 inducers/inhibitors or antiarrhythmic agents.

What is being tested?

The trial is testing the combination of Minnelide (which turns into triptolide in the body) and Osimertinib for treating advanced lung cancer with EGFR mutations. It aims to find the best dose of Minnelide while checking how well it works alongside Osimertinib by blocking a protein needed for cancer cell growth.

What are the potential side effects?

Potential side effects include reactions related to immune system activation such as inflammation in various organs, infusion-related reactions like fever or chills during drug administration, fatigue, digestive issues including nausea or diarrhea, blood disorders like anemia or clotting problems.

Eligibility Criteria

Inclusion Criteria

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

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My tumor has a specific EGFR mutation sensitive to certain treatments.

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My blood clotting time is within the normal range and I'm not on blood thinners.

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My cancer has worsened despite taking osimertinib.

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My lung cancer cannot be treated with surgery or radiation aimed at a cure.

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My blood clotting time is within the normal range and I'm not on blood thinners.

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I am able to care for myself but may not be able to do active work.

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I have taken osimertinib at 80 mg daily without severe side effects.

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My kidney function, measured by creatinine levels or clearance, is within the normal range.

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I can swallow and keep down pills.

Exclusion Criteria

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

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I am currently experiencing diarrhea.

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I have been diagnosed with congenital long QT syndrome.

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I have a history of HIV or hepatitis B/C.

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I have severe heart issues, recent heart attack, irregular heartbeat, or signs of poor blood flow on an ECG.

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I have a condition that affects how my body absorbs nutrients.

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I have a serious health condition that is not under control.

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I do not have any ongoing serious infections needing treatment.

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I am not pregnant or breastfeeding.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

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

Secondary study objectives

Evidence of anti-tumor activity of minnelide when in combination with osimertinib

Incidence of adverse events

Objective response rate

+3 more

Other study objectives

Determination of the exosomes

Evaluation of the microbiome

Side effects data

From 2020 Phase 4 trial • 60 Patients • NCT03853551

10%

Blood creatine phosphokinase increased

10%

Fatigue

Decreased appetite

Diarrhoea

Cough

Mucosal inflammation

Rash

Pain in extremity

Constipation

Thrombocytopenia

Paronychia

Dyspnoea

Dengue fever

Disease progression

Cardio-respiratory arrest

Cataract

Mouth Ulceration

Deep Vein Thrombosis

100%

80%

60%

40%

20%

Study treatment Arm

Single Arm

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (minnelide, osimertinib)Experimental Treatment3 Interventions

Patients receive minnelide PO QD on days 1-21 and osimertinib PO QD on days 1-28. Cycles repeat every 28 days for 6 months in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Osimertinib

2017

Completed Phase 4

~1100

Biopsy

2014

Completed Phase 4

~1090

0 / 17Eligibility 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

Minnelide, a prodrug that converts to the active compound triptolide, inhibits cancer cell proliferation by disrupting transcription and protein degradation processes. Osimertinib, an EGFR inhibitor, blocks the epidermal growth factor receptor, which is frequently mutated in lung cancer, leading to uncontrolled cell growth. These targeted therapies are significant for lung carcinoma patients as they offer more precise treatment options that can effectively inhibit tumor growth and potentially improve survival rates.

Molecular docking studies of Traditional Chinese Medicinal compounds against known protein targets to treat non-small cell lung carcinomas.Tailoring tyrosine kinase inhibitors to fit the lung cancer genome.