BgRT + SBRT + Osimertinib for Non-Small Cell Lung Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: City of Hope Medical Center
Must be taking: Osimertinib
Must not be taking: Antiarrhythmics, QT prolonging drugs
Disqualifiers: Uncontrolled illness, Active infection, HIV, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?This phase II trial tests how well biologically guided radiation therapy (BgRT) and stereotactic body radiation therapy (SBRT) with osimertinib works for the treatment of EGFR positive non-small cell lung carcinoma that has spread from where it first started (primary site) to a limited number of anatomic sites (oligoprogressive). BgRT is radiation that uses specialized imaging to during treatment to target the active tumor and direct radiation to tumors in order to kill and shrink tumor cells. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Osimertinib is in a class of medications called kinase inhibitors. It works by blocking the action of a protein called EGFR that signals cancer cells to multiply. This helps slow or stop the spread of tumor cells. Giving BgRT with SBRT and osimertinib may kill more tumor cells in patients with oligoprogressive EGFR positive non-small cell lung carcinoma.
Will I have to stop taking my current medications?
The trial requires that you stop taking certain medications, such as chemotherapy, radiation therapy, biological therapy, immunotherapy, strong CYP3A4 inducers/inhibitors, class 1A or class III antiarrhythmic agents, and drugs known to prolong the QT interval, within a specified period before starting the trial. However, you can continue taking osimertinib.
What data supports the effectiveness of the drug osimertinib for non-small cell lung cancer?
Osimertinib has shown effectiveness in treating non-small cell lung cancer (NSCLC) with specific genetic mutations, particularly the EGFR T790M mutation, as it significantly improved tumor response rates in clinical trials. It was approved by the FDA based on its ability to shrink tumors in patients who had developed resistance to previous treatments.
12345Is the combination of BgRT, SBRT, and Osimertinib safe for humans?
Osimertinib, a drug used in this combination, has been generally well tolerated in humans with non-small cell lung cancer, with common side effects including diarrhea, rash, and dry skin. Serious side effects occurred in 28% of patients, and 5.6% stopped treatment due to these effects. No new safety concerns were identified in recent studies.
12456What makes the drug osimertinib unique for treating non-small cell lung cancer?
Osimertinib is a unique drug for non-small cell lung cancer because it specifically targets the EGFR T790M mutation, which is often present in patients who have developed resistance to earlier treatments. It is a third-generation drug that works by blocking the signals that help cancer cells grow, and it is taken as a tablet, making it convenient for patients.
13578Eligibility Criteria
This trial is for adults over 18 with advanced non-small cell lung cancer (NSCLC) that has spread to a few sites and have been stable on osimertinib for over 6 months. They must be able to take oral meds, have a life expectancy of at least 6 months, and agree to birth control measures. Excluded are those with certain heart conditions, untreated brain metastases, significant illnesses, or taking drugs that affect the study medication.Inclusion Criteria
I have only been treated with osimertinib for my advanced disease.
I can perform daily activities with minimal assistance.
My tumor has a specific EGFR mutation known to respond to certain treatments.
+11 more
Exclusion Criteria
I haven't taken strong CYP3A4 drugs in the last 14 days.
I have a history of HIV or hepatitis B/C.
I had cancer before, but it was either treated over 5 years ago, was a low-risk type, or was skin/cervical cancer not spreading.
+14 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Patients receive osimertinib daily and undergo BgRT/SBRT every other day for 5 treatments
2 weeks
5 visits (in-person) for radiation therapy
Follow-up
Participants are monitored for safety and effectiveness after treatment with follow-up visits at 1 week, 3 months, 6 months, and 12 months
12 months
4 visits (in-person)
Extension
Participants may receive additional BgRT/SBRT therapy if progression is found, and continue osimertinib in the absence of > 5 sites of progression or unacceptable toxicity
Up to 2 years
Participant Groups
The trial tests biologically guided radiation therapy (BgRT) combined with stereotactic body radiation therapy (SBRT) and osimertinib in patients whose NSCLC has progressed in limited areas. BgRT targets active tumors during treatment while SBRT delivers precise high-dose radiation to minimize damage to healthy tissue.
1Treatment groups
Experimental Treatment
Group I: Treatment (BgRT/SBRT)Experimental Treatment6 Interventions
Patients continue to receive osimertinib PO QD in the absence of unacceptable toxicity. Patients undergo BgRT/SBRT every other day for 5 treatments. Patients then continue to receive osimertinib and are monitored via imaging. If additional progression is found, patients may receive additional BgRT/SBRT therapy. Treatment continues in the absence of \> 5 sites of progression, unacceptable toxicity, or the stopping of osimertinib for more than 4 weeks.
Patients undergo CT scan or PET/CT scan and blood sample collection throughout the study.
Osimertinib is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Tagrisso for:
- Locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R mutations
- Metastatic EGFR T790M mutation-positive NSCLC
🇪🇺 Approved in European Union as Tagrisso for:
- Locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R mutations
- Metastatic EGFR T790M mutation-positive NSCLC
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Yale UniversityNew Haven, CT
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
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.
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.
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.
Osimertinib: A Review in Completely Resected, Early-Stage, EGFR Mutation-Positive NSCLC. [2022]Osimertinib (TAGRISSO®) is an orally administered, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that is approved for the adjuvant treatment of adults with completely resected, stage IB-IIIA, EGFR sensitizing mutation (exon 19 deletion or exon 21 [L858R] substitution)-positive non-small cell lung cancer (NSCLC). In the pivotal ADAURA trial in adults with completely resected, early-stage, EGFR mutation-positive (EGFRm+) NSCLC, osimertinib adjuvant therapy significantly prolonged disease-free survival (DFS) compared with placebo in the overall population of patients with stage IB-IIIA disease, as well as in the primary population of patients with stage II-IIIA disease. A DFS benefit of osimertinib was seen irrespective of whether or not patients received prior adjuvant chemotherapy. Overall survival (OS) data were very immature at the time of the analysis of DFS, and more mature OS data are awaited with interest. Osimertinib adjuvant therapy did not adversely affect health-related quality of life and was generally well tolerated, with a manageable safety profile and no new safety signals identified. Based on the available evidence, osimertinib is thus an appropriate targeted option for the adjuvant treatment of adults with completely resected, stage IB-IIIA, EGFRm+ NSCLC.
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.
New Adjuvant Drug for Lung Cancer. [2023]A new adjuvant treatment, osimertinib (Tagrisso), has been approved for patients with non-small cell lung cancer whose tumors have certain mutations.The most common adverse effects of treatment are leukopenia, lymphopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, and cough.
Acquired BRAF G469A Mutation as a Resistance Mechanism to First-Line Osimertinib Treatment in NSCLC Cell Lines Harboring an EGFR Exon 19 Deletion. [2022]Osimertinib is a new third-generation, epidermal growth factor receptor-tyrosine kinase inhibitor highly selective for the epidermal growth factor receptor with both activating and T790M mutations. A recent phase III trial showed a statistically significant progression-free survival benefit with osimertinib vs. gefitinib or erlotinib as first-line treatment for EGFR-mutated non-small cell lung cancer, and preliminary data are available on resistance mechanisms to first-line osimertinib therapy.
Therapeutic effect of osimertinib plus cranial radiotherapy compared to osimertinib alone in NSCLC patients with EGFR-activating mutations and brain metastases: a retrospective study. [2022]The study aimed to compare the efficacy of osimertinib plus cranial radiotherapy (RT) with osimertinib alone in advanced non-small-cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations and brain metastases (BMs).