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Carcinoma, Non-small Cell LungPhase 3NCT03529084

Phase III Study of Nazartinib (EGF816) Versus Erlotinib/Gefitinib in First-line Locally Advanced / Metastatic NSCLC With EGFR Activating Mutations

A Phase 3 study testing EFG816 and erlotinib or gefitinib in people with Carcinoma, Non-small Cell Lung, run by Novartis Pharmaceuticals.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is a phase III, open label, randomized controlled multi-center global study designed to evaluate the safety and efficacy of single agent nazartinib (EGF816) compared with investigator's choice (erlotinib or gefitinib) in patients with locally advanced or metastatic NSCLC who are treatment naïve and whose tumors… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Non-small Cell Lung
What is being tested?
EFG816 and erlotinib or gefitinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
24 Jul 2018to 3 Jun 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent obtained prior to any screening procedures.
  • Histologically documented locally advanced or metastatic, stage IIIB/ IIIC or stage IV NSCLC with documented EGFR activating mutation (L858R or ex19del)
  • Provision of a tumor tissue sample to allow for retrospective analysis of EGFR mutation status
  • No prior treatment with any systemic antineoplastic therapy in the advanced setting
  • Recovered from all toxicities related to prior treatment
  • Presence of at least one measurable lesion according to RECIST 1.1
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  • Eastern Cooperative Oncology Group (ECOG) performance ≤1
  • Meet the following laboratory values at the screening visit:
  • Absolute Neutrophil Count ≥1.5 x 109/L
  • Platelets ≥75 x 109/L
  • Hemoglobin (Hgb) ≥9 g/dL
  • Creatinine Clearance ≥ 45 mL/min using Cockcroft-Gault formula
  • Total bilirubin ≤1.5 x ULN
  • Aspartate transaminase (AST) ≤ 3.0 x ULN, except for patients with liver metastasis, who may only be included if AST ≤5.0 x ULN
  • Alanine transaminase (ALT) ≤ 3.0 x ULN, except for patients with liver metastasis, who may only be included if ALT ≤5.0 x ULN

Who cannot join

  • Prior treatment with EGFR-TKI.
  • Known T790M positive mutation. Any other known EGFR activating mutations other than L858R or ex19del. Patients whose tumors harbor other EGFR mutations concurrent with L858R or ex19del EGFR mutations are eligible.
  • Symptomatic brain metastases
  • History of interstitial lung disease or interstitial pneumonitis
  • Any medical condition that would, in the investigator's judgment, the patient's in the study due to safety concerns, compliance with clinical study procedures or interpretation of study results
  • Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years..
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  • Presence of clinically significant ophthalmologic abnormalities
  • Bullous and exfoliative skin disorders of any grade
  • Presence or history of microangiopathic hemolytic anemia with thrombocytopenia.
  • Known history of testing positive for human immunodeficiency virus (HIV) infection
  • Cardiac or cardiac repolarization abnormality
  • Major surgery: ≤4 weeks to starting study treatment or who have not recovered from side effects of such procedure.
  • Unable or unwilling to swallow tablets or capsules
  • Female patients who are either pregnant or nursing
  • Women of child bearing potential who refuse or are not able to use a highly effective method of contraception as defined in the study protocol.
  • Sexually active males unless they use a condom during intercourse while taking drug and for 3 months after the last dose of study treatment.
  • Other protocol-defined inclusion/exclusion criteria may apply

About this study

Official title: A Randomized, Open-label, Phase III Study of Single Agent Nazartinib Versus Investigator's Choice (Erlotinib or Gefitinib) as First-Line Treatment in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring EGFR Activating Mutations

This is a phase III, open label, randomized controlled multi-center global study designed to evaluate the safety and efficacy of single agent nazartinib (EGF816) compared with investigator's choice (erlotinib or gefitinib) in patients with locally advanced or metastatic NSCLC who are treatment naïve and whose tumors harbor EGFR activating mutations (L858R or ex19del).

Being tested
EFG816, erlotinib or gefitinib
Keywords
Non small cell lung cancer, NSCLC, EGFR mutation, EGF816, nazartinib, erlotinib, gefitinib
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EFG816Drug

    Also called nazartinib

    It will be administered orally daily.

  • erlotinib or gefitinibDrug

    Investigator's choice between erlotinib or gefitinib. These will be locally sourced.

    Erlotinib will be administered orally daily. Gefitinib will be administered orally daily.

Study groups in NCT03529084
Study groupRoleWhat they receive
EGF816ExperimentalInvestigational treatment arm of EGF816 (nazartinib).
Receives: Drug: EFG816
Investigator's ChoiceActive comparatorInvestigator's Choice (erlotinib or gefitinib).
Receives: Drug: erlotinib or gefitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival (PFS) by Blinded independent review committee (BIRC)

    PFS using central BIRC assessment according to RECIST 1.1, is defined as the time from the date of randomization to the date of the first documented progression (as assessed by BIRC per RECIST 1.1) or death due to any cause, whichever occurs first.

    Measured: Approximately 3 years

Secondary outcomes (16)

  1. Overall Survival

    Overall survival is defined as the time from date of randomization to date of death due to any cause.

    Measured: Approximately 6 years

  2. PFS by investigator

    PFS by Investigator assessment according to RECIST 1.1, is defined as the time from the date of randomization to the date of the first documented progression (as assessed by Investigator per RECIST 1.1) or death due to any cause, whichever occurs first.

    Measured: Approximately 3 years

  3. PFS after next-line of treatment (PFS2) using investigator assessment according to RECIST 1.1

    PFS after next-line of treatment (PFS2) using investigator assessment according to RECIST 1.1 is defined as time from date of randomization to the first documented disease progression (clinical or radiologic) as per investigator assessment on next-line therapy or death from any cause, whichever occurs first.

    Measured: Approximately 4 years

  4. Time to progression in Central Nervous System (CNS) per central neuro-radiologist BIRC

    Time to progression in CNS, defined as time from date of randomization to the date of first documented progression of brain metastases as assessed by central neuro-radiologist BIRC per modified RECIST 1.1 for patients with at least one non-measurable and/or measurable lesion in the brain at baseline.

    Measured: Approximately 3 years

  5. Overall response rate (ORR) by central BIRC

    ORR in accordance with RECIST 1.1. ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR)

    Measured: Approximately 3 years

  6. Duration of response (DOR) by central BIRC

    DOR is defined as the time from date of first documented response (CR and PR) to the date of the first documented progression or death due to underlying cancer, whichever occurs first.

    Measured: Approximately 3 years

  7. Disease control rate (DCR) by central BIRC

    DCR is defined as the percentage of participants with BOR of CR, PR, or stable disease (SD).

    Measured: Approximately 3 years

  8. Time to response (TTR) by central BIRC

    TTR is defined as the time from the date of randomization to the first documented response CR or PR.

    Measured: Approximately 3 years

  9. CNS ORR per central neuro-radiologist BIRC

    CNS ORR in patients with brain metastases who have measurable disease in the brain at baseline review per modified RECIST 1.1

    Measured: Approximately 3 years

  10. CNS DoR per central neuro-radiologist BIRC

    CNS DoR in patients with brain metastases who have measurable disease in the brain at baseline per modified RECIST 1.1

    Measured: Approximately 3 years

  11. Charactise Plasma PK (Cmax) of EGF816

    Peak plasma concentration (Cmax) of EGF816 and its metabolite (LMI258)

    Measured: Day 1 of Cycles 1 to 6 inclusive (21 day cycle)

  12. Charactise Plasma PK (AUC) of EGF816

    Area under the plasma concentration versus time curve (AUC) of EGF816 and its metabolite (LMI258)

    Measured: Day 1 of Cycles 1 to 6 inclusive (21 day cycle)

  13. Charactise Plasma PK (t1/2) of EGF816

    Elimination half life (t1/2) of EGF816 and its metabolite (LMI258)

    Measured: Day 1 of Cycles 1 to 6 inclusive (21 day cycle)

  14. Patient Reported Outcome: Health Related Quality of Life (HRQoL) as measured by QLQ-C30 Questionnaire

    HRQoL as measured by European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 quality of life score

    Measured: Approximately 4 years

  15. Patient Reported Outcome: Health Related Quality of Life (HRQoL) as measured by QLQ-LC13 Questionnaire

    HRQoL as measured by European Organization for Research and Treatment of Cancer (EORTC) QLQ-LC13 quality of life score

    Measured: Approximately 4 years

  16. Patient Reported Outcome: Health Related Quality of Life (HRQoL) as measured by EuroQoL-5 Dimension-5 (EQ-5D-5L) Questionnaire

    Global health status/quality of life score of the EQ-5D-5L

    Measured: Approximately 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 May 2018
  2. Study start24 Jul 2018 (estimated)
  3. Primary completion13 Aug 2020 (estimated)
  4. Study completion3 Jun 2024 (estimated)

Why it stopped: Decision by Sponsor not to continue with the trial.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03529084
Sponsor's protocol ID
CEGF816A2302
Other IDs
2017-003998-34, 2017
Status last verified
Nov 2019
First submitted
18 Apr 2018
Last updated
22 Nov 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing EFG816 and erlotinib or gefitinib in people with Carcinoma, Non-small Cell Lung, run by Novartis Pharmaceuticals.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 22 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) by Blinded independent review committee (BIRC) (time frame: Approximately 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03529084.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2019.

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