30 Participants Needed

Minnelide + Osimertinib for Lung Cancer

Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: City of Hope Medical Center
Must be taking: Osimertinib
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before starting, including strong CYP3A4 inducers/inhibitors, some antiarrhythmic agents, herbal and alternative medications, and specific drugs like clarithromycin, loperamide, and ondansetron. If you're taking any of these, you may need to stop them before joining the trial.

What data supports the effectiveness of the drug combination Minnelide and Osimertinib for lung cancer?

Osimertinib has shown effectiveness in treating non-small-cell lung cancer (NSCLC) with specific mutations, particularly the EGFR T790M mutation, which is a common resistance mechanism to earlier treatments. It has demonstrated efficacy in clinical trials and real-world settings for patients with EGFR-mutant NSCLC.12345

Is the combination of Minnelide and Osimertinib safe for humans?

Osimertinib has been studied for lung cancer and common side effects include diarrhea, rash, dry skin, and nail issues. Serious side effects occurred in about 28% of patients, with some stopping treatment due to these effects. There is no specific safety data available for Minnelide in combination with Osimertinib.25678

What makes the drug combination of Minnelide and Osimertinib unique for lung cancer treatment?

The combination of Minnelide and Osimertinib is unique because it pairs a novel compound, Minnelide, with Osimertinib, a third-generation drug specifically targeting a mutation in lung cancer cells that often leads to resistance against other treatments. This combination aims to enhance effectiveness by addressing resistance mechanisms in non-small cell lung cancer.234910

Research Team

Erminia Massarelli, MD, PhD, MS — The ...

Erminia Massarelli, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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.

Inclusion Criteria

My tumor has a specific EGFR mutation sensitive to certain treatments.
My liver function test is within the required range.
My blood clotting time is within the target range for my anticoagulant therapy.
See 30 more

Exclusion Criteria

I have not taken strong CYP3A4 drugs in the last 14 days.
I have a history of HIV or hepatitis B/C.
I have a serious health condition that is not under control.
See 16 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive minnelide orally once daily on days 1-21 and osimertinib once daily on days 1-28. Cycles repeat every 28 days for 6 months.

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and then every 3 months for 2 years.

2 years

Treatment Details

Interventions

  • Minnelide
  • Osimertinib
Trial OverviewThe 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.
Participant Groups
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.

Find a Clinic Near You

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials
614
Recruited
1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Findings from Research

In a study of 240 advanced non-small-cell lung cancer (NSCLC) patients with acquired resistance to EGFR TKIs, 52.9% had the T790M mutation after rebiopsy, highlighting the mutation's prevalence in treatment resistance.
Patients with the T790M mutation who had previously used osimertinib experienced significantly longer post-progression survival (42.6 months) compared to those without osimertinib (18.0 months) or without the mutation (18.8 months), suggesting osimertinib's effectiveness as a standard treatment for T790M-positive NSCLC.
Post-Progression Survival in Secondary EGFR T790M-Mutated Non-Small-Cell Lung Cancer Patients With and Without Osimertinib After Failure of a Previous EGFR TKI.Chiang, CL., Huang, HC., Shen, CI., et al.[2022]
Osimertinib is an oral medication specifically designed to target the EGFR T790M mutation in advanced non-small cell lung cancer (NSCLC), which helps overcome resistance to previous EGFR TKI therapies.
It received accelerated approval in the USA in November 2015 for patients with metastatic EGFR T790M mutation-positive NSCLC who have progressed after EGFR TKI treatment, and is currently undergoing further development for broader treatment applications.
Osimertinib: First Global Approval.Greig, SL.[2022]
In a retrospective analysis of 32 patients with EGFR T790M-mutant non-small-cell lung cancer, osimertinib showed a 50% objective response rate and a median progression-free survival of 11.3 months, indicating its efficacy in clinical practice.
The median overall survival was 18.3 months, with better outcomes observed in patients without cerebral metastases and those with better performance status, highlighting the importance of these factors in treatment response.
Effectiveness of osimertinib in patients with lung adenocarcinoma in clinical practice - the Expanded Drug Access Program in Poland.Knetki-Wróblewska, M., Kowalski, DM., Czyżewicz, G., et al.[2022]

References

Post-Progression Survival in Secondary EGFR T790M-Mutated Non-Small-Cell Lung Cancer Patients With and Without Osimertinib After Failure of a Previous EGFR TKI. [2022]
Osimertinib: First Global Approval. [2022]
Effectiveness of osimertinib in patients with lung adenocarcinoma in clinical practice - the Expanded Drug Access Program in Poland. [2022]
Pancytopenia During Osimertinib Treatment in a Patient with EGFR-Mutated Non-Small Cell Lung Cancer. [2022]
Real-World Data Of Osimertinib In Patients With Pretreated Non-Small Cell Lung Cancer: A Retrospective Study. [2022]
Osimertinib for the Treatment of Metastatic EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. [2022]
Targeting the Gatekeeper: Osimertinib in EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. [2022]
FDA Benefit-Risk Assessment of Osimertinib for the Treatment of Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor T790M Mutation. [2022]
Increased Expression of IRE1α Associates with the Resistant Mechanism of Osimertinib (AZD9291)-resistant non-small Cell Lung Cancer HCC827/OSIR Cells. [2022]
Acquired EGFR C797G Mutation Detected by Liquid Biopsy as Resistance Mechanism After Treatment With Osimertinib: A Case Report. [2022]