None listed
Conditions
Brief summary
The primary purpose of this trial is to evaluate the efficacy, safety and feasibility of osimertinib and gefitinib for the treatment of EGFR-T790M mutation positive advanced non-small cell lung cancer. Who is it for? You may be eligible to enrol in this trial if you are aged 18 or over and have been diagnosed with EGFR-T790M mutation positive advanced non-small cell lung cancer which has acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). Study details All participants enrolled in this trial will begin with induction therapy which involves taking an osimertinib tablet once per day for eight weeks. Participants will then move onto the alternating phase, which involves alternating four-weekly cycles of treatment with gefitinib and osimertinib (i.e. four weeks gefitinib then four weeks osimertinib) until disease progression or unacceptable side effects. Following progression, some participants may be eligible to continue with alternating treatment or switch to continuous osimertinib treatment until further progression, depending on whether your doctor believes that this would be of benefit to you. All patients will be reviewed up to every four weeks by blood samples, CT scans and side effect assessments. It is hoped that the findings from this trial will provide information on whether alternating treatment with osimertinib and gefitinib is feasible, safe and effective for the treatment of EGFR-T790M mutation positive advanced non-small cell lung cancer.
Interventions
Osimertinib 80 mg daily for 8 weeks (Induction Phase).
Gefitinib 250 mg daily for 4 weeks then Osimertinib 80 mg daily for 4 weeks, and continue alternating (i.e. alternating 4 weekly cylces of each drug) until disease progression or unacceptable toxicity (Alternating Phase).
Following disease progression and if deemed appropriate by the treating Investigator, continuation of alternating therapy OR continuous Osimertinib 80 mg daily until further progression or unacceptable toxicity (Post-Prog
Osimertinib 80 mg daily for 8 weeks (Induction Phase). Gefitinib 250 mg daily for 4 weeks then Osimertinib 80 mg daily for 4 weeks, and continue alternating (i.e. alternating 4 weekly cylces of each drug) until disease progression or unacceptable toxicity (Alternating Phase). Following disease progression and if deemed appropriate by the treating Investigator, continuation of alternating therapy OR continuous Osimertinib 80 mg daily until further progression or unacceptable toxicity (Post-Progression Phase). Both Osimertinib and Gefitinib will be supplied as tablets for oral administration. Adherence will be monitored by counting returned empty drug packets.
Sponsors
University of Sydney
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adults, aged 18 years and older, with histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC 2. Prior therapy with an EGFR-TKI. Patients may also have received additional lines of treatment 3. Documented evidence of EGFR-T790M mutation on tissue and/or plasma sample following disease progression on the most recent EGFR-TKI therapy (T790M mutation status will need to be re-confirmed in the event of an alternative systemic treatment following progression on the most-recent EGFR-TKI therapy). 4. Measurable disease according to RECIST version 1.1. 5. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Exclusion criteria
1. Previous or current treatment with osimertinib or other drugs that target EGFR-T790M mutations, e.g. CO-1686, HM61713, TAS-121 2. Contraindications to investigational product 3. Any unresolved toxicity from prior therapy worse than CTCAE grade 1, except alopecia and grade 2 neuropathy due to prior platinum-based chemotherapy 4. Major surgery within 4 weeks, or palliative radiation therapy within 5 days before enrollment 5. Treatment with prohibited medications (e.g. concurrent anti-cancer therapy including other chemotherapy, or immunotherapy within 14 days prior to treatment) 6. Patients currently receiving (or unable to stop at least 1 week before starting osimertinib) potent inhibitors or inducers of cytochrome P450 (CYP) 3A4 7. Patient with symptomatic central nervous system (CNS) metastases who are neurologically unstable, or require increasing doses of steroids to manage CNS symptoms within 2 weeks prior to starting osimertinib. Patients with leptomeningeal carcinomatosis are also excluded 8. Known history of interstitial lung disease from any cause 9. Life expectancy of less than 3 months 10. Mean QT interval corrected for heart rate (QTc) >= 470 ms OR any clinically important abnormalities in rhythm, conduction or morphology of resting ECG OR any factors that increases the risk of QTc prolongation or risk of arrhythmic events
Outcome results
None listed