Local Ablative Therapy for Treatment of Oligoprogressive, EGFR-Mutated, Non-Small Cell Lung Cancer After Treatment With Osimertinib
Summary
Background: Some non-small-cell lung cancers (NSCLC) have a mutation in a gene that makes a protein called EGFR. This particular cancer can be treated with certain drugs such as erlotinib (Tarceva), gefitinib (Iressa) and osimertinib (Tagrisso). But many tumors become resistant to these drugs because of a second mutation. Researchers want to test if adding local ablative therapy (LAT) extends the benefits of the drug, osimertinib. LAT can include techniques such as surgery, radiofrequency ablation, cryotherapy or radiation therapy. Objective: To test if re-taking osimertinib after LAT is safe, tolerable, and effective for people whose NSCLC has progressed after initial treatment with osimertinib. Eligibility: Adults ages 18 and older with certain types of NSCLC. Participants will be divided into various groups as described below. Design: Participants will be screened with: Medical history Physical exam Blood, urine, and heart tests Tumor scans Eye exam Review of tumor sample. Participants will take the study drug by mouth once a day. They will continue until they can no longer tolerate it or their disease worsens. They will keep a dosage diary. All participants will start each 21-day course with physical exam; blood, urine, and saliva tests; and electrocardiogram. They will have scans every 6 weeks and echocardiogram every 3 months. Groups 1 and 2 will: Start osimertinib right away. Have LAT if their disease progresses and is suitable for LAT. If LAT cannot be performed or LAT consists of a procedure other than surgery, a tumor biopsy will be performed. Re-start osimertinib after LAT, or other treatments if not suitable for LAT. Group 3 will: Have LAT. If LAT consists of a procedure other than surgery, a tumor biopsy will be performed. Start osimertinib after LAT. After participants stop taking the drugs, they will have a final visit. This will include: Medical history Physical exam Blood tests Participants will be called every year for follow-up.
Timeline
- Start
- 2016-04-13
- Primary completion
- 2022-05-25
- Completion
- 2022-09-20
Outcome
Missed primary endpoint
registry All Participants in Cohort 1 vs All Participants in Cohort 2; p = 0.56; Kaplan-Meier NCT02759835 ↗
registry Tyrosine Kinase Inhibitor Naïve Epidermal Growth Factor Receptor *Mutated Non Small Cell Lung Cancer vs EGFR Mutated NSCLC Progressed on Prior 1st/2nd Generation EGFR TKI Therapy &Acquired T790M Mutation vs Epidermal Growth Factor Receptor Mutated Non Small Cell Lung Cancer Progressed on Osimertinib; p = 0.40; Kaplan-Meier NCT02759835 ↗
Publications
- Results Kim C, Xi L, Cultraro CM, Wei F, Jones G, Cheng J, Shafiei A, Pham TH, Roper N, Akoth E, Ghafoor A, Misra V, Monkash N, Strom C, Tu M, Liao W, Chia D, Morris C, Steinberg SM, Bagheri H, Wong DTW, Raffeld M, Guha U. Longitudinal Circulating Tumor DNA Analysis in Blood and Saliva for Prediction of Response to Osimertinib and Disease Progression in EGFR-Mutant Lung Adenocarcinoma. Cancers (Basel). 2021 Jul 3;13(13):3342. doi: 10.3390/cancers13133342.
- Results Roper N, Brown AL, Wei JS, Pack S, Trindade C, Kim C, Restifo O, Gao S, Sindiri S, Mehrabadi F, El Meskini R, Ohler ZW, Maity TK, Venugopalan A, Cultraro CM, Akoth E, Padiernos E, Chen H, Kesarwala A, Smart DK, Nilubol N, Rajan A, Piotrowska Z, Xi L, Raffeld M, Panchenko AR, Sahinalp C, Hewitt S, Hoang CD, Khan J, Guha U. Clonal Evolution and Heterogeneity of Osimertinib Acquired Resistance Mechanisms in EGFR Mutant Lung Cancer. Cell Rep Med. 2020 Apr 21;1(1):100007. doi: 10.1016/j.xcrm.2020.100007.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Osimertinib | Small molecule | 80 mg | Oral |
| Subject | Osimertinib | Small molecule | 160 mg | Oral |