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Trial registered on ANZCTR


Trial ID
ACTRN12617000720314
Ethics application status
Approved
Date submitted
17/05/2017
Date registered
18/05/2017
Date last updated
9/03/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Phase 2 trial of alternating osimertinib with gefitinib in patients with EGFR-T790M mutation positive advanced non-small cell lung cancer
Scientific title
Phase 2 trial to determine the efficacy, safety, and feasibility of alternating osimertinib with gefitinib in patients with EGFR-T790M mutation positive advanced non-small cell lung cancer
Secondary ID [1] 291984 0
CTC 0152 / ALTG 16/005
Universal Trial Number (UTN)
Trial acronym
OSCILLATE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
EGFR-T790M mutation positive advanced non-small cell lung cancer 303334 0
Condition category
Condition code
Cancer 302768 302768 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 298107 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 302157 0
Progression free survival rate according to RECIST v1.1
Timepoint [1] 302157 0
At 12 months from the date of enrollment
Secondary outcome [1] 334988 0
Feasibility of alternating osimertinib and gefitinb defined by whether each participant is able to complete 6 months of study treatment without any dose interruption due to grade 3 - 5 adverse events
Timepoint [1] 334988 0
At 6 months after starting study treatment
Secondary outcome [2] 334989 0
Time to Progression (TTP) according to RECIST v1.1
Timepoint [2] 334989 0
Measured every 8 weeks from time of enrollment to time of disease progression
Secondary outcome [3] 334990 0
Objective tumour response rate (OTRR) defined as the proportion of participants with a confirmed complete or partial response according to RECIST v1.1, and response confirmed with a subsequent assessment at least 4 weeks later.
Timepoint [3] 334990 0
Assessed every 8 weeks from the time of enrollment until disease progression
Secondary outcome [4] 334991 0
Overall survival (OS)
Timepoint [4] 334991 0
Time from enrollment until date of death
Secondary outcome [5] 334992 0
Safety assessed by collection of adverse events (AEs) graded as per NCI-CTCAE v4.03
Timepoint [5] 334992 0
AEs collected from the time of enrollment every 4 weeks until 30 days after last study dose
Secondary outcome [6] 334993 0
Tertiary outcome: Changes in plasma cfDNA levels for activating EGFR mutations and EGFR-T790M mutation over time
Timepoint [6] 334993 0
Day 1 of each Cycle, Day 15 of Cycles 3 and 4, and end of alternating treatment phase
Secondary outcome [7] 334994 0
Tertiary outcome: Mechanisms of resistance in patients progressing on alternating osimertinib and gefitinb as identified in cfDNA (or where possible tumour biopsy) - Exploratory outcome
Timepoint [7] 334994 0
Blood samples collected at Day 1 of each Cycle, Day 15 of Cycles 3 and 4, at the time of disease progression, and when all study treatment is complete. Optional tumour biopsy sample collected at time of disease progression.

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
A total sample size of 45 participants (allowing for 4 ineligible or non-evaluable) will distinguish the observed proportion alive and progression free at 12 months from 45% (not worthy of further research) versus 65% (worthy of further research) using a Simon’s two-stage minimax design with 90% power with a 1-sided type 1 error rate of 10%.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA,VIC
Recruitment hospital [1] 10341 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 10342 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [3] 10343 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [4] 10344 0
Liverpool Hospital - Liverpool
Recruitment hospital [5] 10345 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [6] 10346 0
Concord Repatriation Hospital - Concord
Recruitment hospital [7] 10347 0
St George Hospital - Kogarah
Recruitment hospital [8] 10348 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment hospital [9] 10349 0
Gosford Hospital - Gosford
Recruitment hospital [10] 10350 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [11] 10351 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment postcode(s) [1] 22012 0
3000 - Melbourne
Recruitment postcode(s) [2] 22013 0
2298 - Waratah
Recruitment postcode(s) [3] 22014 0
3065 - Fitzroy
Recruitment postcode(s) [4] 22015 0
2170 - Liverpool
Recruitment postcode(s) [5] 22016 0
2010 - Darlinghurst
Recruitment postcode(s) [6] 22017 0
2139 - Concord
Recruitment postcode(s) [7] 22018 0
2217 - Kogarah
Recruitment postcode(s) [8] 22019 0
2050 - Camperdown
Recruitment postcode(s) [9] 22020 0
2250 - Gosford
Recruitment postcode(s) [10] 22021 0
2065 - St Leonards
Recruitment postcode(s) [11] 22022 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 296494 0
Commercial sector/Industry
Name [1] 296494 0
AstraZeneca
Address [1] 296494 0
47 Talavera Rd, Macquarie Park NSW 2113
Country [1] 296494 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
NHMRC Clinical Trials Centre
Lifehouse Level 6
119–143 Missenden Road
Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 295456 0
None
Name [1] 295456 0
Address [1] 295456 0
Country [1] 295456 0
Other collaborator category [1] 279580 0
Other Collaborative groups
Name [1] 279580 0
Australasian Lung Cancer Trials Group
Address [1] 279580 0
Level 2, 11 Finchley Street Milton QLD 4064
Country [1] 279580 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297715 0
Royal Prince Alfred Hospital
Ethics committee address [1] 297715 0
Research Ethics and Governance Office
Royal Prince Alfred Hospital
Camperdown NSW 2050
Ethics committee country [1] 297715 0
Australia
Date submitted for ethics approval [1] 297715 0
13/03/2017
Approval date [1] 297715 0
18/05/2017
Ethics approval number [1] 297715 0

Summary
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 74926 0
Prof Ben Soloman
Address 74926 0
Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne VIC 3000
Country 74926 0
Australia
Phone 74926 0
+61 3 8559 5000
Fax 74926 0
Email 74926 0
Ben.Solomon@petermac.org
Contact person for public queries
Name 74927 0
Ms Uzma Rayani
Address 74927 0
NHMRC Clinical Trials Centre
Lifehouse Level 6
119–143 Missenden Road
Camperdown NSW 2050
Country 74927 0
Australia
Phone 74927 0
+61 2 9562 5000
Fax 74927 0
Email 74927 0
oscillate@ctc.usyd.edu.au
Contact person for scientific queries
Name 74928 0
Ms Uzma Rayani
Address 74928 0
NHMRC Clinical Trials Centre
Lifehouse Level 6
119–143 Missenden Road
Camperdown NSW 2050
Country 74928 0
Australia
Phone 74928 0
+61 2 9562 5000
Fax 74928 0
Email 74928 0
oscillate@ctc.usyd.edu.au