Phase 2 trial of alternating osimertinib with gefitinib in patients with EGFR-T790M mutation positive advanced non-small cell lung cancer
- Conditions
- Cancer - Lung - Non small cellEGFR-T790M mutation positive advanced non-small cell lung cancer
- Registration Number
- ACTRN12617000720314
- Lead Sponsor
- niversity of Sydney
- Brief Summary
What was the trial about? About 1 in 6 Australians with lung cancer have a changed gene (mutation) for the epidermal growth factor receptor (EGFR). This mutation in the EGFR gene makes this particular cancer grow. To specifically target the effects of this mutation, standard treatments include drugs like gefitinib and osimertinib. These drugs are often effective for a period of time, but then stop working and the lung cancer becomes less sensitive to the drug. This is called drug resistance. Laboratory studies suggested that switching the two drugs gefitinib and osimertinib back and forth (alternating treatment) may delay the development of drug resistance. The primary outcome of the trial was the proportion of people whose cancer remained under control at 12 months (progression-free survival at 12 months). Other outcomes measured were the feasibility of this treatment approach, the proportion of people whose cancer had shrunk in response to treatment (tumour response rate), and safety. How well did alternating treatment work? The results of alternating treatment in OSCILLATE were similar to those in other trials of osimertinib alone. 68% of people in OSCILLATE were able to complete 6 months of treatment without any delays or interruptions due to side effects, suggesting that the alternating approach was safe and feasible. The lung cancer was still under control 12 months after starting treatment in 38% of the participants.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 49
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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Progression free survival rate according to RECIST v1.1[ At 12 months from the date of enrollment]
- Secondary Outcome Measures
Name Time Method