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Trial registered on ANZCTR


Registration number
ACTRN12623000552684
Ethics application status
Approved
Date submitted
7/03/2023
Date registered
23/05/2023
Date last updated
15/04/2024
Date data sharing statement initially provided
23/05/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
OCEANiC: A Phase II, Open-label, Multi-centre Clinical Trial of Osimertinib With or Without Adjuvant Chemotherapy Guided by Tumour NGS Co-mutation Status and ctDNA Detection in Patients With
Stage IIA-IIIA EGFR-Mutant Non Small Cell Lung Cancer Following Complete Surgical Resection
Scientific title
OCEANiC: A Phase II, Open-label, Multi-centre Clinical Trial on effect of Osimertinib, With or Without Adjuvant Chemotherapy, Guided by Tumour Next Generation Sequencing (NGS) Co-mutation Status and circulating tumour DNA (ctDNA) Detection on disease-free survival in Patients With Stage IIA-IIIA epidermal growth factor receptor (EGFR)-Mutant Non Small Cell Lung Cancer Following Complete Surgical Resection
Secondary ID [1] 308847 0
TOGA 20/007
Universal Trial Number (UTN)
Trial acronym
OCEANiC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
EGFR-Mutant Non Small Cell Lung Cancer Following Complete Surgical Resection 328807 0
Condition category
Condition code
Cancer 325817 325817 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
During screening patients are divided into 2 noncomparative cohorts, (low vs higher risk cancer recurrence) which is based on tumour tissue co-mutation status and the detection of ctDNA in plasma collected up to four weeks post-surgery. The tumour tissue used will be a sample from the surgical resection of the primary NSCLC the participant has already undergone. The plasma will be a blood test.

Cohort 1 (low risk): Includes participants with absence of ctDNA and no co-mutations. Participants will receive osimertinib 80 mg orally, once daily, for up to 3 years or until disease recurrence, unacceptable toxicity. Participants will need to return osimertinib bottles at each visit to monitor treatment compliance.

Cohort 2 (high risk): Includes participants with presence of ctDNA and/or presence of tumour co-mutations. Participants will receive 4 cycles of platimun doublet chemotherapy followed by osimertinib 80 mg orally, once daily, for up to 3 years or until disease recurrence, unacceptable toxicity or consent withdrawal, whichever is sooner. Participants will need to return osimertinib bottles at each visit to monitor treatment compliance.

For participants in cohort 1, osimertinib should commence within 10 weeks following surgery.
For participants in cohort 2, osimertinib should commence within 26 weeks following surgery.
Intervention code [1] 325289 0
Treatment: Drugs
Comparator / control treatment
Nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 333995 0
The primary objective of the study is to evaluate Disease Free Survival (DFS) at 3 years in the respective treatment groups.
Timepoint [1] 333995 0
DFS is defined as the interval from date of registration to the date of first evidence of disease recurrence or death, whichever occurs first. This outcome will be reviewed at 3 years from end of treatment. The date of first disease recurrence based on imaging (PET-CT, MRI) is that of the first positive scan, even if this is determined in retrospect.
Secondary outcome [1] 418993 0
overall survival (OS)
Timepoint [1] 418993 0
Overall Survival (OS) is defined as the time from registration to the date of death due to any cause. Participants will be followed for up to 6 years post enrolment (up to 3 years on treatment and 3 years post-treatment)
Secondary outcome [2] 418995 0
Patient-reported outcomes (PROs) assessing cancer related quality of life using the EORTC QLQ-C30
Timepoint [2] 418995 0
PROs will be collected at the time of registration, at the beginning of week 9 (cohort 1) or week 10 (cohort 2), then 12-weekly in year 1 (corresponding to clinical assessment at the beginning of weeks 13, 25, 37 & 61 +/- 7 days), then annually in years 2, 3, 4 & 5 (corresponding to clinical assessment at the beginning of weeks 109, 157, 209 & 261 +/- 7 days).
Secondary outcome [3] 419937 0
The survival benefits participants judge necessary to make adjuvant chemotherapy worthwhile, and the factors influencing their preferences
Timepoint [3] 419937 0
The Preferences for Adjuvant Chemotherapy questionnaire will be administered on a single occasion approximately 26 weeks after registration.
Secondary outcome [4] 419938 0
Adverse Events (AEs) according to the NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0)
Timepoint [4] 419938 0
AEs will be collected 3-weekly during chemotherapy, then 4-weekly for the first 12 weeks of osimertinib, then 12-weekly until osimertinib is permanently discontinued.
Secondary outcome [5] 421358 0
Patient-reported outcomes (PROs) assessing lung cancer specific quality of life using QLQ-LC29
Timepoint [5] 421358 0
PROs will be collected at the time of registration, at the beginning of week 9 (cohort 1) or week 10 (cohort 2), then 12-weekly in year 1 (corresponding to clinical assessment at the beginning of weeks 13, 25, 37 & 61 +/- 7 days), then annually in years 2, 3, 4 & 5 (corresponding to clinical assessment at the beginning of weeks 109, 157, 209 & 261 +/- 7 days).
Secondary outcome [6] 421359 0
Patient-reported outcomes (PROs) using EuroQoL EQ-5D-5L instruments.
Timepoint [6] 421359 0
PROs will be collected at the time of registration, at the beginning of week 9 (cohort 1) or week 10 (cohort 2), then 12-weekly in year 1 (corresponding to clinical assessment at the beginning of weeks 13, 25, 37 & 61 +/- 7 days), then annually in years 2, 3, 4 & 5 (corresponding to clinical assessment at the beginning of weeks 109, 157, 209 & 261 +/- 7 days).
Secondary outcome [7] 422215 0
Tertiary and Exploratory Objectives. The exploratory objectives of the study are to examine:
associations between clinical outcomes and possible prognostic biomarkers (tissue and circulating).
Timepoint [7] 422215 0
Blood will be collected Prior to study treatment, then 6-monthly for 3 years (corresponding to clinical assessment at the beginning of weeks 25, 61, 85, 109, 133 and 157 +/- 7 days) and at disease recurrence.

Baseline Tumour samples will be from diagnostic biopsy or surgical specimen for co-mutation testing (per eligibility criteria). If participant consents, an optional sample will also be collected at recurrance.

Eligibility
Key inclusion criteria
1. Adults, aged 18 years or older, with histological diagnosis of NSCLC. Patients with mixed small cell lung cancer histology are not eligible.
2. Stage IIA to IIIA NSCLC according to AJCC 8th edition.
3. Complete surgical resection of the primary NSCLC is mandatory.
3.1. All gross tumour surgically removed at the end of surgery.
3.2. All surgical resection margins must be microscopically negative.
3.3. Resection may be accomplished by open or VATS techniques
3.4. Surgery may consist of segmentectomies, lobectomy, sleeve resection, bi-lobectomy or pneumonectomy based on the intraoperative findings with appropriate lymph node sampling/mapping as determined by the surgeon. Patients who have only had wedge resections are not eligible.

4. Complete recovery from surgery at the time of registration. No more than 8 weeks may have elapsed between surgery and registration. Complete post-operative wound healing must have occurred following surgery.
5. Documented evidence of EGFR mutation (at any time since the initial diagnosis of NSCLC) known to be sensitive to osimertinib. These include exon 19 deletions, L858R (exon 21), G719X (exon 18), L861Q (exon 21), S768I (exon 20) and T790M (exon 20). Compound mutations involving any of the listed sensitising mutations are allowed.
6. ECOG Performance Status of 0 or 1 within 14 days prior to planned treatment start date.
7. Tumour tissue available from diagnostic biopsy or surgical specimen for co-mutation testing.
8. Adequate organ system function within 14 days prior to planned treatment start date:
• Bone marrow function
i. Platelets more than or equal to 100 x 109/L
ii. Absolute neutrophil count (ANC) more than or equal to 1.5 x 109/L
iii. Haemoglobin more than or equal to 90 g/L
• Liver function
i. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 x upper limit of normal (ULN)
ii. Total bilirubin less than or equal to 1.5 x ULN or 3 x ULN in the presence of documented Gilbert’s Syndrome (unconjugated hyperbilirubinaemia).
• Renal function
i. Measured creatinine clearance more than or equal to 45 mL/min (e.g. by 51Cr-EDTA or 99mTc-DTPA renography) or Calculated creatinine clearance more than or equal to 45 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance.

9. MRI scan of the brain must be performed at any time between diagnosis and registration.
10. Baseline ECG with QTc <470ms and no clinically significant arrhythmias.
11. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments.
12. Signed, written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Previous diagnosis of another lung cancer within 5 years prior to registration.
2. Prior systemic treatment for NSCLC including prior EGFR pathway inhibitor treatment.
3. History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib.
4. Post-operative radiotherapy (PORT) planned.
5. Prior radiation to lung and/or mediastinum.
6. Known history of interstitial lung disease (ILD) or drug-induced pneumonitis requiring steroid treatment, or any evidence of clinically active ILD.
7. Treatment with an investigational drug within five half-lives of the compound or 3 months, whichever is greater.
8. Significant history of cardiovascular disease. Any clinically important abnormalities in rhythm conduction or morphology of resting ECG e.g. Complete left bundle branch block, third degree heart block and second degree heart block. Patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, electrolyte abnormalities, Congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes.
9. Significant history of peripheral vascular or cerebrovascular disease.
10. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, active hepatitis B, hepatitis C, or HIV. Chronic hepatitis B carrier with undetectable hepatitis DNA level is allowed. Serological testing is not mandatory unless clinically indicated.
11. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib.
12. History of another concurrent active malignancy that requires ongoing treatment.
13. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
14. Treatment with prohibited medications which may interact with study treatment.
15. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.
16. Pregnancy, lactation, or inadequate contraception. Participants must be post-menopausal, infertile, or use a reliable means of contraception. Participants of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Participants who are having a sexual relationship in which their partner could become pregnant must have been surgically sterilised or use a (double if required) barrier method of contraception.
17. Involvement in the planning and/or conduct of the study (applies to both NHMRC CTC staff and/or staff at the study site).

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

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,SA,WA,VIC
Recruitment hospital [1] 24135 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 24136 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [3] 24137 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [4] 24138 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [5] 24139 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment hospital [6] 24140 0
GenesisCare - St Leonards - St Leonards
Recruitment hospital [7] 24141 0
Liverpool Hospital - Liverpool
Recruitment hospital [8] 24142 0
The Prince Charles Hospital - Chermside
Recruitment hospital [9] 24143 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [10] 26412 0
Westmead Hospital - Westmead
Recruitment hospital [11] 26413 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 39651 0
2050 - Camperdown
Recruitment postcode(s) [2] 39652 0
2065 - St Leonards
Recruitment postcode(s) [3] 42389 0
2145 - Westmead
Recruitment postcode(s) [4] 39653 0
2170 - Liverpool
Recruitment postcode(s) [5] 39647 0
3000 - Melbourne
Recruitment postcode(s) [6] 39648 0
3065 - Fitzroy
Recruitment postcode(s) [7] 39649 0
3084 - Heidelberg
Recruitment postcode(s) [8] 39650 0
3168 - Clayton
Recruitment postcode(s) [9] 39654 0
4032 - Chermside
Recruitment postcode(s) [10] 42390 0
5042 - Bedford Park
Recruitment postcode(s) [11] 39655 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 313068 0
Commercial sector/Industry
Name [1] 313068 0
AstraZeneca Australia Pty Ltd
Country [1] 313068 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
Camperdown NSW 2006
Country
Australia
Secondary sponsor category [1] 314758 0
None
Name [1] 314758 0
Address [1] 314758 0
Country [1] 314758 0
Other collaborator category [1] 282571 0
Other Collaborative groups
Name [1] 282571 0
The Thoracic Oncology Group of Australasia (TOGA)
Address [1] 282571 0
PO Box 1103 Thornbury VIC 3071
Country [1] 282571 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312319 0
RPAH Human Research Ethics Committee
Ethics committee address [1] 312319 0
CAMPERDOWN NSW 2050
Ethics committee country [1] 312319 0
Australia
Date submitted for ethics approval [1] 312319 0
23/01/2023
Approval date [1] 312319 0
07/03/2023
Ethics approval number [1] 312319 0
X23-0014

Summary
Brief summary
The purpose of this study is to investigate whether we can use co-mutation NGS profiling (looks for gene changes in your cancer tissue) and circulating tumour (ct) DNA (looks for fragments of the tumour moving through the blood stream. These fragments are known as circulating tumour DNA (ctDNA) and carry genetic information) to determine which patients with EGFR mutant non small-cell lung cancer can safely avoid chemotherapy.

Who is it for?
You may be eligible for this study if you are an adult with non small-cell lung cancer, with a mutation in epidermal growth factor receptor (referred to as EGFR mutation) that has had their tumour completely resected by surgery.

Study details:
During screening NGS profiling and ctDNA testing will be performed. The NGS and ctDNA results will be used to determine if your cancer is at higher or lower risk of returning. Participants with a higher risk of their cancer returning will have up to 4 cycles (over 12 weeks) of chemotherapy followed by up to 3 years of daily osimertinib. Participants with a lower risk of their cancer returning will have osimertinib daily for up to 3 years.

The following assessments will be conducted throughout the trial: physical exam, CT scans, MRI, blood tests, pregnancy test, ECG and questionnaires.

It is hoped that this study will help determine if osimertinib alone may provide similar benefits with less toxicity, improved quality of life and reduced health care costs, to chemotherapy and osimertinib.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 124234 0
A/Prof A/Professor Chee Khoon Lee
Address 124234 0
Levels 4-6 Medical Foundation Building, 92-94 Parramatta Rd, Camperdown NSW 2050
Country 124234 0
Australia
Phone 124234 0
+61 2 7906 5618
Fax 124234 0
Email 124234 0
chee.lee@sydney.edu.au
Contact person for public queries
Name 124235 0
Ms Kate Ford
Address 124235 0
Levels 4-6 Medical Foundation Building, 92-94 Parramatta Rd, Camperdown NSW 2050
Country 124235 0
Australia
Phone 124235 0
+61 2 9562 5000
Fax 124235 0
Email 124235 0
oceanic.study@sydney.edu.au
Contact person for scientific queries
Name 124236 0
Ms Kate Ford
Address 124236 0
Levels 4-6 Medical Foundation Building, 92-94 Parramatta Rd, Camperdown NSW 2050
Country 124236 0
Australia
Phone 124236 0
+61 2 9562 5000
Fax 124236 0
Email 124236 0
oceanic.study@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
De-identified participant trial data will be entered directly into a web based CRF held by the NHMRC Clinical Trials Centre, University of Sydney. Access will only be granted to the research staff directly involved with the trial.
Individual participant data will not be made publicly available. Only grouped data which does not identify individual participants will be published.


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.