Minnelide + Osimertinib for Lung Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: City of Hope Medical Center
Must be taking: Osimertinib
Must not be taking: CYP3A4 inducers, Antiarrhythmics, Herbal meds
Disqualifiers: HIV, Hepatitis B/C, Cardiac disease, others
No Placebo Group
Breakthrough Therapy
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.
12345Is 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.
25678What 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.
234910Eligibility 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.
+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.
+16 more
Trial 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
Participant Groups
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.
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
Research Locations NearbySelect from list below to view details:
City of Hope Medical CenterDuarte, CA
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Who Is Running the Clinical Trial?
City of Hope Medical CenterLead Sponsor
National Cancer Institute (NCI)Collaborator
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 is effective in non-small-cell lung cancer (NSCLC) with an acquired epidermal growth factor receptor (EGFR) T790M mutation, the most common resistance mechanism to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs).
Osimertinib: First Global Approval. [2022]Osimertinib (Tagrisso(™), AZD9291) is an oral, third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that is being developed by AstraZeneca for the treatment of advanced non-small cell lung cancer (NSCLC). Osimertinib has been designed to target the EGFR T790M mutation that is often present in NSCLC patients with acquired EGFR TKI resistance, while sparing wild-type EGFR. In November 2015, the tablet formulation of osimertinib was granted accelerated approval in the USA for the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC (as detected by an FDA-approved test) who have progressed on or after EGFR TKI therapy. Osimertinib has also been granted accelerated assessment status for this indication in the EU, and is in phase III development for first- and second-line and adjuvant treatment of advanced EGFR mutation-positive NSCLC in several countries. Phase I trials in patients with advanced solid tumours are also being conducted. This article summarizes the milestones in the development of osimertinib leading to this first approval for NSCLC.
Effectiveness of osimertinib in patients with lung adenocarcinoma in clinical practice - the Expanded Drug Access Program in Poland. [2022]Osimertinib is a third-generation, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has demonstrated efficacy in the treatment of EGFR-mutant non-small-cell lung cancer (NSCLC) in prospective clinical trials.
Pancytopenia During Osimertinib Treatment in a Patient with EGFR-Mutated Non-Small Cell Lung Cancer. [2022]Osimertinib is an irreversible tyrosine kinase inhibitor approved for the treatment of metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). In clinical trials, osimertinib has exhibited excellent activity and less toxicity compared to gefitinib, erlotinib and standard chemotherapy.
Real-World Data Of Osimertinib In Patients With Pretreated Non-Small Cell Lung Cancer: A Retrospective Study. [2022]Osimertinib is an oral, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeted for both EGFR sensitizing mutations and T790M resistance mutation in patients with non-small-cell lung cancer (NSCLC). We assessed efficacy and safety of osimertinib in patients with pretreated NSCLC in a real-world setting.
Osimertinib for the Treatment of Metastatic EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. [2022]On November 13, 2015, the FDA granted accelerated approval to osimertinib (TAGRISSO; AstraZeneca), a breakthrough therapy-designated drug for the treatment of patients with metastatic EGFR T790M mutation-positive non-small cell lung cancer, as detected by an FDA-approved test, with progression on or after EGFR tyrosine kinase inhibitor therapy. Approval was based on durable tumor response rates in two single-arm, multicenter trials: the dose extension cohort of a first-in-human trial (FIH; AURA extension; n = 201) and a fixed-dose, activity-estimating trial (AURA2; n = 210). Osimertinib was administered at 80 mg orally once daily. The objective response rates (ORR) per blinded independent committee review were 57% [95% confidence interval (CI), 50-64) in AURA extension and 61% (95% CI, 54-68) in AURA2. Median duration of response (DOR) could not be estimated. Supportive efficacy data from 63 patients in the dose-finding part of the FIH trial demonstrated an ORR of 51% (95% CI, 38-64), with a median DOR of 12.4 months. Common adverse events (AE) evaluated in 411 patients included diarrhea (42%), rash (41%), dry skin (31%), and nail toxicity (25%). Grade 3 to 4 AEs occurred in 28% of patients, and 5.6% discontinued treatment due to AEs. Clin Cancer Res; 23(9); 2131-5. ©2016 AACR.
Targeting the Gatekeeper: Osimertinib in EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. [2022]In 2015, the FDA approved an unprecedented number of new therapies for non-small cell lung cancer (NSCLC), among them therapies addressing specific genomic tumor subsets in the setting of development of resistance to first-line targeted therapy. Osimertinib (Tagrisso, formerly AZD9291; AstraZeneca) is indicated for patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, who have progressed on or after EGFR tyrosine kinase inhibitor therapy. It received breakthrough therapy designation, priority review status, and accelerated approval from the FDA. Clin Cancer Res; 23(3); 618-22. ©2016 AACR.
FDA Benefit-Risk Assessment of Osimertinib for the Treatment of Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor T790M Mutation. [2022]On March 30, 2017, the U.S. Food and Drug Administration (FDA) approved osimertinib for the treatment of patients with metastatic, epidermal growth factor receptor (EGFR) T790M mutation-positive, non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, whose disease has progressed following EGFR tyrosine kinase inhibitor (TKI) therapy. Approval was based on demonstration of a statistically significant difference in the primary endpoint of progression-free survival (PFS) when comparing osimertinib with chemotherapy in an international, multicenter, open-label, randomized trial (AURA3). In this confirmatory trial, which enrolled 419 patients, the PFS hazard ratio for osimertinib compared with chemotherapy per investigator assessment was 0.30 (95% confidence interval 0.23-0.41), p < .001, with median PFS of 10.1 months in the osimertinib arm and 4.4 months in the chemotherapy arm. Supportive efficacy data included PFS per blinded independent review committee demonstrating similar PFS results and an improved confirmed objective response rate per investigator assessment of 65% and 29%, with estimated median durations of response of 11.0 months and 4.2 months, in the osimertinib and chemotherapy arms, respectively. Patients received osimertinib 80 mg once daily and had a median duration of exposure of 8 months. The toxicity profile of osimertinib compared favorably with the profile of other approved EGFR TKIs and chemotherapy. The most common adverse drug reactions (>20%) in patients treated with osimertinib were diarrhea, rash, dry skin, nail toxicity, and fatigue. Herein, we review the benefit-risk assessment of osimertinib that led to regular approval, for patients with metastatic NSCLC harboring EGFR TKI whose disease has progressed on or after EGFR TKI therapy.
Increased Expression of IRE1α Associates with the Resistant Mechanism of Osimertinib (AZD9291)-resistant non-small Cell Lung Cancer HCC827/OSIR Cells. [2022]Osimertinib (OSI), also known as AZD9291, is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of non-small cell lung cancer (NSCLC) patients.
Acquired EGFR C797G Mutation Detected by Liquid Biopsy as Resistance Mechanism After Treatment With Osimertinib: A Case Report. [2022]Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor approved for the treatment of T790M-positive non-small-cell lung cancer. More recently, osimertinib demonstrated improved disease control compared to other EGFR-TKIs. Multiple mechanisms of resistance have been described in T790M-positive patients who experienced treatment failure with osimertinib.