A trial to learn how well osimertinib (AZD9291) works to prevent cancer from coming back after surgery and how safe it is compared to the placebo in adults with non-small cell lung cancer with an EGFR mutation.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Astrazeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical,Diagnostic,Therapeutic Techniques and Equipment [E]-Surgical Procedures, Operative [E04], Diseases [C] - Hemic and Lymphatic Diseases [C15], Psychiatry and Psychology [F] - Behavioral Disciplines and Activities [F04], Diseases [C] - Neoplasms [C04]

Trial duration

21 Oct 2015 → ongoing

Decision date (initial)

2024-06-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2023-506524-82-00

EudraCT number

2015-000662-65

ClinicalTrials.gov

NCT02511106

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To assess the efficacy of Osimertinib compared to placebo as measured by disease free survival (DFS)

Secondary objectives 4

1. To further assess the efficacy of Osimertinib compared with placebo by assessment of DFS rate at 2, 3, 4 and 5 years, of OS and OS rate at 2, 3, 4 and 5 years.
2. To assess the effect of Osimertinib compared with placebo on health related quality of life (HRQoL) by assessment of patient health-related quality of life and symptoms (HRQoL) using SF-36 questionnaire (version 2).
3. To characterize the pharmacokinetics (PK) of Osimertinib and its metabolites (AZ5104 and AZ7550) by assessment of PK exposure parameters derived from plasma concentrations of Osimertinib and metabolites AZ5104 and AZ7550.
4. To assess the safety and tolerability profile of Osimertinib compared with placebo by assessment of number and severity of adverse events, clinical chemistry, hematology, urinalysis, vital signs, physical examination, body weight, digital electrocardiogram (ECG), left Ventricular Ejection Fraction (LVEF), World Health Organization (WHO) Performance Status and Ophthalmologic assessment.

Conditions and MedDRA coding

Stage IB-IIIA non-small cell lung carcinoma, with a centrally confirmed, common sensitising EGFR mutations (Ex19del and L858R either alone or in combination with other EGFR mutations), following complete tumour resection with or without adjuvant chemotherapy

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Male or female, aged at least 18 years.
2. Histologically confirmed diagnosis of primary non small lung cancer (NSCLC) on predominantly non-squamous histology.
3. MRI or CT scan of the brain must be done prior to surgery as it is considered standard of care.
4. Patients must be classified post-operatively as Stage IB, II or IIIA on the basis of pathologic criteria.
5. Confirmation by the central laboratory that the tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations including T790M.
6. Complete surgical resection of the primary NSCLC is mandatory. All gross disease must have been removed at the end of surgery. All surgical margins of resection must be negative for tumour.
7. Complete recovery from surgery and standard post-operative therapy (if applicable) at the time of randomization.
8. World Health Organization Performance Status of 0 to 1.
9. Female patients should be using adequate contraceptive measures, should not be breast feeding, and must have a negative pregnancy test prior to first dose of study drug; or female patients must have an evidence of non-child-bearing potential.

Exclusion criteria 9

1. Treatment with any of the following: - Pre-operative or post-operative or planned radiation therapy for the current lung cancer - Pre-operative (neo-adjuvant) platinum based or other chemotherapy - Any prior anticancer therapy - Prior treatment with neoadjuvant or adjuvant EGFR-TKI at any time - Major surgery (including primary tumour surgery, excluding placement of vascular access within 4 weeks of the first dose of study drug - Patients currently receiving medications or herbal supplements known to be potent inducers of CYP3A4 - Treatment with an investigational drug within five half-lives of the compound or any of its related material.
2. Patients who have had only segmentectomies or wedge resections.
3. History of other malignancies, except: adequately treated nonmelanoma skin cancer, curatively treated in-situ cancer, or other solid tumours curatively treated with no evidence of disease for > 5 years following the end of treatment.
4. Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy.
5. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
6. 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.
7. Any of the following cardiac criteria: - Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs, using the screening clinic ECG machine-derived QTc value. - Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG. - Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval.
8. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
9. Inadequate bone marrow reserve or organ-function.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease free survival (DFS) using investigator assessments.

Secondary endpoints 6

1. Assessment of Disease free survival (DFS) rate at 2 years, 3 years, 4 years and 5 years.
2. Analysis of Overall Survival (OS)
3. Assessment of Overall Survival (OS) rate at 2 years, 3 years, 4 years and 5 years.
4. Assessing of patient health-related quality of life and symptoms (HRQoL) using SF-36 questionnaire (version 2, standard)
5. PK exposure parameters derived from plasma concentrations of Osimertinib and metabolites AZ5104 and AZ7550. Pharmacokinetics data from this study will be analysed using a population PK approach and may also form part of a pooled analysis with other Osimertinib studies; results from these analyses will be reported separately from the CSR.
6. Safety and tolerability endpoints assessed by number and severity of adverse events, clinical chemistry, haematology, urinalysis, vital signs, physical examination, body weight, digital electrocardiogram (ECG), left Ventricular Ejection Fraction (LVEF), World Health Organization (WHO) Performance Status and Ophthalmologic assessment.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Astrazeneca AB

Sponsor organisation

Astrazeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

Astrazeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

Astrazeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

7 EU/EEA countries · 37 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 59 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications