First-line Treatment With Osimertinib in EGFR-mutated Non-small Cell Lung Cancer

NCT03804580 | Active Not Recruiting Phase 2

• 1 other identifier: REK 2018/1028
• Study Type: interventional
• Target: 100
• Locations: 4 countries
• Sites: 10

Brief Summary

Phase II, single-arm study to assess the safety and efficacy of osimertinib (80 mg, orally, once daily) as first-line therapy in patients with EGFR mutation-positive, locally advanced or metastatic non-small cell lung cancer (NSCLC) who have not previously treated with an epidermal growth factor tyrosine kinase inhibitor agent.

Conditions

Lung Cancer

Keywords

Targeted therapy; EGFR

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  Measured by RECIST 1.1

  12 weeks

Study Arms (1)

osimertinib

EXPERIMENTAL

All patients recieve osimertinib

Drug: osimertinib

Interventions

osimertinib DRUG

Non-randomized trial, all patients receive therapy

osimertinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated, written informed consent.
• Age \> 18 years.
• Documented EGFR mutation in exon 18-21, except insertions in exon 20, based on tissue analysis.
• ECOG status 0-2 and a minimum life expectancy of 12 weeks.
• Patients with untreated, mild or moderately symptomatic and measurable brain metastases are eligible, but will be allocated to cohort A (see excl. point 6). Patients with pre-treated, stable and asymptomatic brain metastases will be allocated to cohort B.
• At least one lesion, not previously irradiated and not chosen for biopsy during the study screening period, that can be accurately measured at baseline according to RECIST 1.1.
• Females should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
• Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
• Women under 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) levels in the post-menopausal range for the institution
• Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
• Male subjects must be willing to use barrier contraception.

You may not qualify if:

• Previous systemic treatment against metastatic NSCLC.
• Subjects currently receiving (or unable to stop using) potent inducers of CYP3A4. Patients must stop using CYP3A4 inducers at least 3 weeks prior to treatment with osimertinib (see appendix A).
• Subjects with spinal cord compression unless they have completed definitive therapy, are not on steroids and have had a stable neurological status for at least 2 weeks after completion of definitive therapy and steroids.
• Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
• Previous malignancy (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, oesophageal, colon, endometrial, cervical, melanoma or breast) unless a complete remission was achieved at least 2 years prior to study entry.
• 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.
• Exclude based on any of the following cardiac criteria:
• Mean resting corrected QT interval (QTc) \> 470 msec obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc value
• 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
• 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
• Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
• Inadequate bone marrow reserve or organ function (as demonstrated by any of the following laboratory values:
• Absolute neutrophil count \< 1.5 x 109/L
• Platelet count \< 100 x 109/L
• Haemoglobin \< 90 g/L

Sponsors & Collaborators

• Vestre Viken Hospital Trust: lead

Study Sites (10)

Aarhus University Hospital

Aarhus, Denmark

Location

Herlev Hospital

Copenhagen, Denmark

Location

Rigshospitalet

Copenhagen, Denmark

Location

Odense University Hospital

Odense, Denmark

Location

National Cancer Institute

Vilnius, Lithuania

Location

Drammen Hospital - Vestre Viken HF

Drammen, N-3004, Norway

Location

Oslo University Hospital - Ullevaal

Oslo, N-0450, Norway

Location

St Olavs Hospital

Trondheim, N-7008, Norway

Location

Lund University Hospital

Lund, Sweden

Location

Karolinska University Hospital

Stockholm, Sweden

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

osimertinib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Odd Terje Brustugun, MD PhD

  Drammen Hospital - Vestre Viken

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2019
• First Posted: January 15, 2019
• Study Start: December 1, 2018
• Primary Completion: June 1, 2025
• Study Completion: December 31, 2025
• Last Updated: May 7, 2024

Record last verified: 2024-05

Locations

DK (4); LI (1); SE (2); NO (3)