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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03804580
Recruitment Status : Active, not recruiting
First Posted : January 15, 2019
Last Update Posted : April 7, 2022
Information provided by (Responsible Party):
Vestre Viken Hospital Trust

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.

Condition or disease Intervention/treatment Phase
Lung Cancer Drug: osimertinib Phase 2

Detailed Description:

This is a 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.

Subjects will have to provide a biopsy sample (fresh or archival) for molecular testing at inclusion. If feasible, a biopsy will also be sampled when partial response is achieved and at the time of disease progression on osimertinib. Liquid biopsies will be sampled throughout the treatment period.

Subjects should continue on study treatment until RECIST 1.1-defined progression or until a treatment criterion is met. There is no maximum duration of treatment as subjects may continue to receive investigational product beyond RECIST1.1-defined progression as long as they are continuing to show clinical benefit, as judged by the investigator.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: First-line Treatment With Osimertinib in EGFR-mutated Non-small Cell Lung Cancer, Coupled to Extensive Translational Studies
Actual Study Start Date : December 1, 2018
Estimated Primary Completion Date : August 31, 2023
Estimated Study Completion Date : August 31, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Osimertinib

Arm Intervention/treatment
Experimental: osimertinib
All patients recieve osimertinib
Drug: osimertinib
Non-randomized trial, all patients receive therapy

Primary Outcome Measures :
  1. Objective response rate [ Time Frame: 12 weeks ]
    Measured by RECIST 1.1

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Provision of signed and dated, written informed consent.
  2. Age > 18 years.
  3. Histologically or cytologically documented locally advanced or metastatic NSCLC not amenable to curative surgery or radiotherapy. Patients that have received systemic adjuvant therapy for non-metastatic disease in the past will need a new biopsy before inclusion.
  4. Documented EGFR mutation in exon 18-21, except insertions in exon 20, based on tissue analysis.
  5. ECOG status 0-2 and a minimum life expectancy of 12 weeks.
  6. 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.
  7. 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.
  8. 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.
  9. Male subjects must be willing to use barrier contraception.

Exclusion Criteria:

  1. Previous systemic treatment against metastatic NSCLC.
  2. Major surgery within 4 weeks of inclusion
  3. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of inclusion
  4. 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).
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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
  10. 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.
  11. 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
    • Alanine aminotransferase (ALT) > 2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases
    • Aspartate aminotransferase (AST) > 2.5 times ULN if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases
    • Total bilirubin > 1.5 times ULN if no liver metastases or > 3 times ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or liver metastases
    • Serum creatinine >1.5 times ULN concurrent with creatinine clearance <50 mL/min [measured or calculated by Cockcroft and Gault equation]-confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN
  12. History of hypersensitivity of active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib.
  13. Treatment with an investigational drug within five half-lives of the compound or 3 months, whichever is greater.
  14. Previous enrolment in the present study or previous treatment with osimertinib.
  15. 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.
  16. Women who are pregnant or breast-feeding, or have a positive (urine or serum) pregnancy test prior to study entry
  17. Involvement in the planning and/or conduct of the study (investigator staff and/or staff at the study site).
  18. Judgment by the investigator that the subject should not participate in the study if the subject is unlikely to comply with study procedures, restrictions and requirements.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03804580

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Aarhus University Hospital
Aarhus, Denmark
Herlev Hospital
Copenhagen, Denmark
Copenhagen, Denmark
Odense University Hospital
Odense, Denmark
National Cancer Institute
Vilnius, Lithuania
Drammen Hospital - Vestre Viken HF
Drammen, Norway, N-3004
Oslo University Hospital - Ullevaal
Oslo, Norway, N-0450
St Olavs Hospital
Trondheim, Norway, N-7008
Lund University Hospital
Lund, Sweden
Karolinska University Hospital
Stockholm, Sweden
Sponsors and Collaborators
Vestre Viken Hospital Trust
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Principal Investigator: Odd Terje Brustugun, MD PhD Drammen Hospital - Vestre Viken
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Responsible Party: Vestre Viken Hospital Trust
ClinicalTrials.gov Identifier: NCT03804580    
Other Study ID Numbers: REK 2018/1028
First Posted: January 15, 2019    Key Record Dates
Last Update Posted: April 7, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Vestre Viken Hospital Trust:
Targeted therapy
Additional relevant MeSH terms:
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Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action