Minnelide and Osimertinib for the Treatment of Advanced EGFR Mutated Non-Small Cell Lung Cancer

Running, not enrolling · Phase 1

Conditions studied: Advanced Lung Non-Small Cell Carcinoma, Locally Advanced Lung Non-Small Cell Carcinoma, Stage III Lung Cancer AJCC v8, Stage IIIA Lung Cancer AJCC v8, Stage IIIB Lung Cancer AJCC v8, Stage IIIC Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8, Unresectable Lung Non-Small Cell Carcinoma

In brief

This phase Ib trial tests the side effects and best dose of minnelide when given together with osimertinib for the treatment of non-small cell lung cancer that has spread to other places in the body (advanced) and has a change (mutation) in a gene called EGFR. Minnelide is a biologically inactive compound that can be broken down in the body to produce a drug that rapidly releases the active compound triptolide when exposed to phosphatases in the bloodstream. Sometimes, mutations in the EGFR gene cause EGFR proteins to be made in higher than normal amounts on some types of cancer cells. This causes cancer cells to divide more rapidly. Osimertinib may stop the growth of tumor cells by blocking EGFR that is needed for cell growth in this type of cancer. Minnelide and osimertinib may work better in treating patients with EGFR mutant advanced non-small cell lung cancer.

Key facts

Study ID: NCT05166616
Run by: City of Hope Medical Center
People needed: 8
Starts: 2022-03-07
Expected to finish: 2027-10-28
Last updated by the study team: 2026-03-05

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Documented informed consent of the participant and/or legally authorized representative
Assent, when appropriate, will be obtained per institutional guidelines
Agreement to two research biopsies
If tumor is unbiopsiable or not safely biopsied, exceptions may be granted with study principal investigator (PI) approval
Age: >= 18 years
Karnofsky performance >= 70%
Histologically confirmed advanced non-small cell lung cancer (NSCLC). Patients with locally advanced NSCLC must not be candidates for surgical resection, radiation, or chemoradiation with curative intent
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
Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Tumor progression after receiving standard/approved osimertinib
Fully recovered from the acute toxic effects (except alopecia) to =< grade 1 to prior anti-cancer therapy. Grade 2 neuropathy is allowed
Absolute neutrophil count (ANC) >= 1,500/mm\^3 (within 14 days prior to day 1 of protocol therapy)
NOTE: Growth factor is not permitted within 14 days of ANC assessment
Platelets >= 100,000/mm\^3 (within 14 days prior to day 1 of protocol therapy)
NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment
Hemoglobin >= 9 g/dL (within 14 days prior to day 1 of protocol therapy)
Total bilirubin =< 1.5 X ULN (unless has Gilbert's disease). Total bilirubin < 3 x ULN in the presence of documented Gilbert's disease (within 14 days prior to day 1 of protocol therapy)
Aspartate aminotransferase (AST) =< 2.5 x upper limit of normal (ULN) (if liver metastases are present, then =< 5 x ULN is allowed) (within 14 days prior to day 1 of protocol therapy)
Alanine aminotransferase (ALT) =< 2.5 x ULN if liver metastases are present, then =< 5 x ULN is allowed) (within 14 days prior to day 1 of protocol therapy)
Alkaline phosphatase =< 2.5 x ULN if liver metastases are present, then =< 5 x ULN is allowed) (within 14 days prior to day 1 of protocol therapy)
Serum creatinine within normal limits, OR creatinine clearance of >= 60 mL/min per 24 hour urine test for patients with creatinine levels above ULN (within 14 days prior to day 1 of protocol therapy)
Creatinine clearance (CrCl, by Cockcroft-Gault) is utilized for all patients to allow for evaluation of the effect of CrCl on the minnelide/triptolide exposures
If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN (within 14 days prior to day 1 of protocol therapy)
If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) =< 1.5 x ULN (within 14 days prior to day 1 of protocol therapy)

You may not qualify if…

Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within 21 days prior to day 1 of protocol therapy (6 weeks for nitrosoureas or Mitomycin C). Exceptions to this exclusion are brain radiation and osimertinib
Biological therapy, immunotherapy within 21 days prior to day 1 of protocol therapy
Strong CYP3A4 inducers/ inhibitors within 14 days prior to day 1 of protocol therapy
Patients receiving class 1A or class III antiarrhythmic agents within 14 days prior to Day 1 of protocol therapy
Herbal and alternative (eg. turmeric, cannabidiol, ginseng) medications within 7 days prior to Day 1 of protocol therapy
Clarithromycin, loperamide, ondansetron within 7 days prior to day 1 of protocol therapy
History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
Active diarrhea
Clinically significant uncontrolled illness
Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
Prior malignancy other than carcinoma in situ of the cervix, or nonmelanoma skin cancer, unless that prior malignancy was diagnosed and definitively treated 5 or more years prior to study entry with no subsequent evidence of recurrence. Patients with a history of low grade (Gleason score =< 6 = Gleason Group 1) localized prostate cancer will be eligible even if diagnosed less than 5 years prior to study entry
Females only: Pregnant or breastfeeding
Any malabsorption condition
Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures.
New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on electrocardiogram (ECG)
Clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroid medication for 1 week prior to the first dose of study drug and have completed radiation 2 weeks prior to the first dose of study drug
Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
Diagnosis of congenital long QT syndrome
Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Where it is running

City of Hope Medical Center — Duarte, California, United States

Full record on ClinicalTrials.gov

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