A Global Study to Assess the Effects of Osimertinib Following Chemoradiation in Patients With Stage III Unresectable Non-small Cell Lung Cancer (LAURA)

• Register: ClinicalTrials.gov
• Last refreshed on: 29 April 2024
• Main ID: NCT03521154
• Date of registration: 20/04/2018
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca
• Public title: A Global Study to Assess the Effects of Osimertinib Following Chemoradiation in Patients With Stage III Unresectable Non-small Cell Lung Cancer (LAURA) LAURA
• Scientific title: A Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter, International Study of Osimertinib as Maintenance Therapy in Patients With Locally Advanced, Unresectable EGFR Mutation-positive Non-Small Cell Lung Cancer (Stage III) Whose Disease Has Not Progressed Following Definitive Platinum-based Chemoradiation Therapy (LAURA).
• Date of first enrolment: July 19, 2018
• Target sample size: 216
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03521154
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Argentina, Brazil, China, Hungary, India, Japan, Korea, Republic of, Malaysia, Mexico, Peru, Russian Federation, Spain, Taiwan, Thailand, Turkey, United States, Vietnam

Contacts

• Name: Shun Lu, MD
• Affiliation: Shanghai Chest Hospital, Shanghai, China

• Name: Suresh S Ramalingam, MD
• Affiliation: Emory University School of Medicine, Atlanta, U.S.

Key inclusion & exclusion criteria

Inclusion Criteria

1. Male or female aged at least 18 years.

2. Patients with histologically documented NSCLC of predominantly non-squamous Pathology
who present with locally advanced, unresectable (Stage III) disease (according to
Version 8 of the International Association for the Study of Lung Cancer [IASLC]
Staging Manual in Thoracic Oncology).

3. The tumor harbours one of the two common EGFR mutations known to be associated with
EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR
mutations, assessed by cobas® EGFR Mutation Test v2 (Roche Diagnostics) or
FoundationOne® test in a CLIA certified (USA sites) or an accredited local laboratory
(sites outside of the USA) or by central testing (cobas® v2 only).

4. Patients must have received either concurrent chemoradiation or sequential
chemoradiation including at least 2 cycles of platinum based chemotherapy and a total
dose of radiation of 60 Gy ±10% (54 to 66 Gy).

5. Chemoradiation must be completed =6 weeks prior to randomization.

6. Patients must not have had disease progression during or following definitive
platinum-based, chemoradiation therapy.

7. World Health Organization (WHO) performance status of 0 or 1.

8. Life expectancy >12 weeks at Day 1.

9. Female patients who are not abstinent (in line with the preferred and usual lifestyle
choice) must be using adequate contraceptive measures, must 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-childbearing potential.

Exclusion Criteria

1. Mixed small cell and non-small cell lung cancer histology

2. History of interstitial lung disease (ILD) prior to chemoradiation

3. Symptomatic pneumonitis following chemoradiation

4. Any unresolved toxicity Common Terminology Criteria for Adverse Events (CTCAE) > Grade
2 from the prior chemoradiation therapy

5. Any of the following cardiac criteria:

- Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs

- Any clinically important abnormalities in rhythm, conduction, or morphology of
resting ECG

- Patient with any factors that increase the risk of QTc prolongation or risk of
arrhythmic events such as heart failure, hypokalaemia, 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

6. Inadequate bone marrow reserve or organ function

7. History of other malignancies, except: adequately treated non-melanoma skin cancer or
lentigo maligna , curatively treated in-situ cancer, or other solid tumors curatively
treated with no evidence of disease for > 5 years following the end of treatment and
which, in the opinion of the treating physician, do not have a substantial risk of
recurrence of the prior malignancy.

8. 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).

9. 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

10. Prior treatment with any prior chemotherapy, radiation therapy, immunotherapy or
investigational agents for NSCLC outside of that received in the definitive setting
for Stage III disease (chemotherapy and radiotherapy in SCRT and CCRT regimens is
allowed for treatment of Stage III disease).

11. Prior treatment with EGFR-TKI therapy

12. Major surgery as defined by the investigator within 4 weeks of the first dose of study
drug.

13. Patients currently receiving (unable to stop use prior to receiving the first dose of
study treatment) medications or herbal supplements known to be strong inducers of
CYP3A4 (at least 3 weeks prior to receiving the first dose of study drug).

14. Contraindication to MRI, including but not limited to, claustrophobia, pace makers,
metal implants, intracranial surgical clips and metal foreign bodies



Age minimum: 18 Years
Age maximum: 130 Years
Gender: All

Health Condition(s) or Problem(s) studied

Non Small Cell Lung Cancer (Stage III)

Intervention(s)

Drug: Placebo Osimertinib 80mg/40mg

Drug: Osimertinib 80mg/40mg

Primary Outcome(s)

Progression-free survival (PFS) [Time Frame: Approximately 13 months]

Secondary Outcome(s)

Time to CNS PFS [Time Frame: Approximately 13 months]

Objective response rate (ORR) [Time Frame: Approximately 13 months]

PFS in patients with EGFR Ex19del or L858R mutation [Time Frame: Approximately 13 months]

Time to second subsequent therapy (TSST) [Time Frame: Approximately 21 months]

Tumor shrinkage [Time Frame: Approximately 13 months]

Duration of response (DoR) [Time Frame: Approximately 13 months]

Time to first subsequent therapy (TFST) [Time Frame: Approximately 13 months]

Disease control rate (DCR) [Time Frame: Approximately 13 months]

Patients reported disease-related symptoms and HRQoL by EORTC QLQ-LC13 and EORTC QLQ-30 questionnaires [Time Frame: Approximately 21 months]

Incidence of Adverse Events (AEs) [Time Frame: Approximately 13 months]

Overall survival (OS) [Time Frame: Approximately 45 months]

PFS in patients with EGFR mutations Ex19del or L858R detectable in plasma-derived ctDNA [Time Frame: Approximately 13 months]

Plasma concentrations of osimertinib and AZD5104 [Time Frame: Trough concentrations at Week 4,12 and 24]

Time to death or distant metastases (TTDM) [Time Frame: Approximately 13 months]

Time to treatment discontinuation [Time Frame: Approximately 13 months]

Second progression free survival on a subsequent treatment (PFS2) [Time Frame: Approximately 13 months]

Secondary ID(s)

D5160C00048

2018-001061-16

Source(s) of Monetary Support

Please refer to primary and secondary sponsors