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Stage I Non-Small Cell Lung CancerPhase 2NCT03433469

Osimertinib in Treating Participants With Stage I-IIIA EGFR-mutant Non-small Cell Lung Cancer Before Surgery

A Phase 2 study testing Osimertinib and Therapeutic Conventional Surgery in people with Stage I Non-Small Cell Lung Cancer and Stage IA Non-Small Cell Lung Cancer, run by University of California, San Francisco at 3 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This phase II trial studies how well osimertinib works in treating participants with stage I-IIIA Epithelial Growth Factor Receptor (EGFR) -mutant non-small cell lung cancer before surgery. Osimertinib may stop the growth of tumor cells by blocking mutant EGFR signaling in cancer cells. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Osimertinib and Therapeutic Conventional Surgery
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
3 sitesUnited States
Study dates
31 Jul 2018to 30 Sep 2027
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Males and females >=18 years of age
  • Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), performed on a biopsy that occurred within the last 90 days. This biopsy can be deferred if the procedure is deemed to represent an unacceptable safety risk to the patient by the Principal Investigator and as long as the patient has a prior biopsy showing non-small cell lung cancer.
  • Documented activating EGFR mutation (Exon 19 deletion, T790M, or L858R) on tumor samples by Clinical Laboratory Clinical Laboratory Improvement Amendments (CLIA)-approved test
  • Patients treated with osimertinib or another EGFR tyrosine kinase inhibitors (TKI) (including erlotinib, afatinib, gefitinib, \& rocelitinib) are eligible if they received no more than 28 days of treatment, and if there is no evidence of grade 2 or greater treatment adverse events possibly related to treatment with the EGFR TKI.
  • Positron emission tomography (PET)-computed tomography (CT) within the last 60 days showing radiographic stage I to IIIa lung cancer (mediastinal staging biopsy is allowed but not required)
  • Brain magnetic resonance imaging (MRI) (or CT if contraindication to MRI) within the last 60 days showing no evidence of metastatic disease
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  • Documentation that the patient is a candidate for surgical resection of their lung cancer by an American Board of Thoracic Surgery certified surgeon
  • The patient must have a tumor size >=1 centimeter (cm) in its longest diameter.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1
  • Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment, with the exception of alopecia and grade 2 prior platinumtherapy-related neuropathy is allowed
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
  • Bilirubin =< 1.5 x ULN, (Patients with documented Gilbert's syndrome and conjugated bilirubin within the normal range may be allowed into the study; in this event, it will be documented that the patient was eligible based on conjugated bilirubin levels)
  • Potassium and magnesium within normal range, patients may receive supplements to meet this requirement
  • Leukocytes > 3,000/microliter (mcL)
  • Hemoglobin >= 9 g/dL, with no blood transfusions in the 28 days prior to study entry
  • Absolute neutrophil count > 1,500/mcL
  • Platelets > 100,000/mcL
  • Creatinine Clearance (CrCl) > 50 mL/min for patients with serum creatinine (SCr) > 1.5 x upper limit of normal (ULN)
  • Ability to swallow oral medications
  • Women of childbearing potential (WoCBP) must have a negative serum pregnancy test within 3 days prior to the first dose of study treatment and agree to use highly effective contraception, during the study and for 90 days following the last dose of osimertinib
  • Women of childbearing potential (WoCBP): women between menarche and menopause who have not been permanently or surgically sterilized and are capable of procreation
  • Women NOT of childbearing potential: women who are permanently or surgically sterilized or postmenopausal
  • Permanent sterilization includes hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy but excludes bilateral tubal occlusion; tubal occlusion is considered a highly effective method of birth control but does not absolutely exclude possibility of pregnancy; (the term occlusion refers to both occluding and ligating techniques that do not physically remove the oviducts)
  • Women who have undergone tubal occlusion should be managed on trials as if they are of WoCBP (e.g. undergo pregnancy testing etc., as required by the study protocol)
  • Women will be considered postmenopausal if they are amenorrhoeic for 12 months without an alternative medical cause; the following age-specific requirements apply:
  • Women under 50 years old will be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone and follicle-stimulating hormone levels in the postmenopausal range
  • Women over 50 years of age will be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatments
  • Acceptable contraception methods are:
  • Total sexual abstinence (abstinence must be for the total duration of the trial and the follow-up period)
  • Vasectomized sexual partner plus male condom (with participant assurance that partner received post-vasectomy confirmation of azoospermia)
  • Tubal occlusion plus male condom
  • Intra-uterine device - provided coils are copper-banded, plus male condom
  • Intra-uterine system (IUS) levonorgestrel IUS (e.g., Mirena), plus male condom
  • Medroxyprogesterone injections (Depo-Provera) plus male condom
  • Etonogestrel implants (e.g., Implanon, Norplan) plus male condom
  • Normal and low dose combined oral contraceptive pills, plus male condom
  • Norelgestromin / ethinylestradiol transdermal system plus male condom
  • Intravaginal device (e.g., ethinylestradiol and etonogestrel) plus male condom
  • Cerazette (desogestrel) plus male condom (Cerazette is currently the only highly efficacious progesterone based pill)
  • Unacceptable Contraception Methods The following methods are considered not to be highly effective and are therefore not acceptable contraceptive methods:
  • Triphasic combined oral contraceptives
  • All progesterone only pills except, Cerazette
  • All barrier methods, if intended to be used alone
  • Non-copper containing intra-uterine devices
  • Fertility awareness methods
  • Coitus interruptus
  • Men with a female partner of childbearing potential must have either had a prior vasectomy agree to use effective contraception as described in the full protocol for at least 14 days prior to administration of the first dose of study treatment, during the study, and for 90 days following the last dose of osimertinib

Who cannot join

  • Leptomeningeal carcinomatosis or other central nervous system (CNS) metastases
  • Stage IIIB, or distant metastases (including malignant pleural effusion) identified on PET-CT scan or biopsy (PET abnormalities that are negative for malignancy on biopsy will be considered on a case by case basis
  • 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
  • Patients who are known to be serologically positive for human immunodeficiency virus (HIV)
  • Active second malignancy, i.e. patient known to have potentially fatal cancer present for which he/she may be (but not necessarily) currently receiving treatment; patients with a history of malignancy that has been completely treated, with no evidence of that cancer currently, are permitted to enroll in the trial provided all chemotherapy for prior malignancy was completed > 12 months prior and/or bone marrow transplant > 2 years prior
  • Patients who are currently receiving treatment with contraindicated corrected QT interval (QTc) prolonging medications or potent CYP3A4 inducers, if that treatment cannot be either discontinued or switched to a different medication prior to first day of study treatment. All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects
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  • Any of the following cardiac abnormalities or history:
  • 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
  • Treatment with prohibited medications (concurrent anticancer therapy including chemotherapy, radiation, hormonal treatment [except corticosteroids and megesterolacetate], or immunotherapy) =< 14 days prior to treatment with osimertinib
  • 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 jeopardize compliance with the protocol, or known active infection including chronic active hepatitis B, hepatitis C and human immunodeficiency virus (HIV); screening for chronic conditions is not required; patients with chronic hepatitis B virus (HBV) with negative HBV viral load on appropriate antiviral therapy will be permitted, if able to continue appropriate antiviral therapy throughout treatment period
  • Active tuberculosis
  • Signs or symptoms of infection within 2 weeks prior to first day of study
  • Therapeutic oral or intravenous (IV) antibiotics within 2 weeks prior to first day of study treatment:
  • Patients receiving prophylactic antibiotics (eg, to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible
  • Class II to IV heart failure as defined by the New York Heart Association functional classification system
  • Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction (LVEF) < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate, to be eligible
  • Patients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction (unstable angina, congestive heart failure, myocardial infarction within the previous 3 months; coronary angioplasty, or stenting or bypass grafting within the past 6 months; cardiac ventricular arrhythmias requiring medication; any history of second (2nd) or third (3rd) degree atrioventricular conduction defects)
  • Females who are pregnant or breastfeeding
  • Presence of active gastrointestinal (GI) disease (including GI bleeding or ulceration) or other condition that could affect GI absorption (e.g. malabsorption syndrome, history of biliary tract disease), including refractory nausea or vomiting, or chronic GI disease which may affect absorption or tolerance to oral medications
  • History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib
  • Involvement in the planning and/or conduct of the study (applies to both investigator staff and/or staff at the study site)
  • Participation in another clinical study with an investigational product during the last 2 months or within five half-lives of the compound, whichever is longer
  • Uncontrolled medical, psychological, familial, sociological, or geographical conditions that interfere with the patient?s safety, ability to provide informed consent, or ability to comply with the protocol

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • University of Colorado

    Aurora, Colorado, 80045

  • University of California, Davis

    Davis, California, 95864

  • University of California, San Francisco

    San Francisco, California, 94143

Other trials in United States

About this study

Official title: A Phase II Study to Evaluate Neoadjuvant Osimertinib Therapy in Patients With Surgically Resectable, EGFR-Mutant Non-Small Cell Lung Cancer

This phase II trial studies how well osimertinib works in treating participants with stage I-IIIA Epithelial Growth Factor Receptor (EGFR) -mutant non-small cell lung cancer before surgery. Osimertinib may stop the growth of tumor cells by blocking mutant EGFR signaling in cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the efficacy of osimertinib as neoadjuvant therapy in patients with surgically resectable EGFR-mutant non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

  1. To evaluate the safety of osimertinib given as neoadjuvant therapy in early stage EGFR-mutant NSCLC participants.

II. To evaluate whether neoadjuvant osimertinib treatment increases the frequency of tumors that are unresectable due to adverse events or disease progression.

III. To evaluate secondary measures of clinical efficacy in early stage EGFR-mutant NSCLC patients treated with osimertinib induction therapy.

TERTIARY OBJECTIVES:

  1. To evaluate long-term measures of efficacy in patients treated with osimertinib neoadjuvant therapy.

II. To explore tissue and cell-free biomarkers that may be predictive of response or primary resistance to osimertinib neoadjuvant therapy.

OUTLINE:

Participants receive osimertinib orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection of their cancer.

After completion of study treatment, participants are followed up at 30 days then every 3 months for up to 1 year.

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.

Study groups in NCT03433469
Study groupRoleWhat they receive
Treatment (osimertinib)ExperimentalParticipants receive 80mg osimertinib orally, once a day (PO QD) on days 1-28. Treatment repeats every 28 days for a minimum of 1 cycle prior to surgery in the absence of disease progression or unacceptable toxicity. Investigators will have the option to give a second cycle of study drug prior to surgery if clinically indicated. Depending on the timing of the final scans, patients may ultimately receive up to two weeks additional therapy with study drug beyond end of cycle 1 (or cycle 2) while awaiting surgery. Patients then undergo surgical resection of their cancer. No treatment with the study drug will be given after surgery.
Receives: Drug: Osimertinib; Procedure: Therapeutic Conventional Surgery

What is being measured

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

  1. Percentage of Participants With a Major Pathological Response (MPR)

    Tumors that exhibit =< 10% viable tumor will meet the criteria for a major pathological response. MPR will be determined in patients who receive at least one dose of study drug and become ineligible for surgery either because of disease progression or adverse event will be deemed not to have achieved MPR. The major pathological response rate will be reported with 95% confidence intervals.

    Measured: Up to 1 year

Secondary outcomes (9)

  1. Objective Response Rates (ORR)

    The percentage of participants with a best overall response rate of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and by investigator's assessment will be determined from the time of treatment until surgery. The frequency and percentages of patients with a best ORR of CR, PR, SD, or PD will be determined. The ORR for each response type will be reported with 95% confidence intervals.

    Measured: Up to 70 days

  2. Mean Disease-free Survival (DFS)

    DFS will be calculated as 1+ the number of days from date of surgical resection to documented radiographic relapse/progression or death due to any cause over a period of 60 months. The Kaplan-Meier analysis will be used to calculate the median DFS with 95% confidence interval.

    Measured: Up to 5 years

  3. Disease-free Survival Rate (DFS)

    DFS will be calculated as 1+ the number of days from date of surgical resection to documented radiographic relapse/progression or death due to any cause over a period of 60 months. The 5-year DFS rate will be calculated as the percentage of patients who are disease free at 5 years. This will be calculated using the Kaplan-Meier method

    Measured: Up to 5 years

  4. Overall Survival (OS)

    5-year OS rate will be calculated using the Kaplan-Meier method . OS will be defined as the 1+ the number of days from surgical resection to death due to any cause over a period of 60 months. The Kaplan-Meier analysis will be used to calculate the median OS with 95% confidence interval.

    Measured: Up to 5 years

  5. Median Percentage Change in Tumor Burden (Depth of Response)

    Depth of response (DpR) will be defined as the percentage change in tumor burden by RECIST criteria at best response versus baseline imaging. DpR will be summarized using descriptive statistics.

    Measured: Up to 1 year

  6. Pathologic Complete Response Rate (pCR)

    The pCR is defined as absence of (0%) viable tumor present histologically in the resected tumor specimen

    Measured: Up to 1 year

  7. Percentage of Participants With of Treatment-related Adverse Events (AEs)

    The percentage of participants with treatment-related adverse events will be reported. Adverse events will be classified according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

    Measured: Up to 1 year

  8. Percentage of Participants Unable to Undergo Surgical Resection

    Rate of conversion from operable to non-operative will be recorded as rate of patients initially assessed as surgically resectable, who are subsequently unable to undergo surgical resection due to either treatment-related adverse events (AEs) or disease progression.

    Measured: Up to 70 days

  9. Percentage of Surgical Complications

    Rate of surgical complications occurring prior to the end of treatment visit will be reported

    Measured: Up to 1 year

Timeline

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

  1. First posted14 Feb 2018
  2. Study start31 Jul 2018
  3. Primary completion31 Jan 2023
  4. Study completion30 Sep 2027 (estimated)

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03433469
Sponsor's protocol ID
17658
Other IDs
NCI-2018-00019
Status last verified
Mar 2026
First submitted
25 Jan 2018
Last updated
30 Mar 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Blakely CM, Urisman A, Gubens MA, Mulvey CK, Allen GM, Shiboski SC, Rotow JK, Chakrabarti T, Kerr DL, Aredo JV, Bacaltos B, Gee M, Tan L, Jones KD, Devine WP, Doebele RC, Aisner DL, Patil T, Schenk EL, Bivona TG, Riess JW, Coleman M, Kratz JR, Jablons DM. Neoadjuvant Osimertinib for the Treatment of Stage I-IIIA Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer: A Phase II Multicenter Study. J Clin Oncol. 2024 Sep 10;42(26):3105-3114. doi: 10.1200/JCO.24.00071. Epub 2024 Jul 19.

    PubMed 39028931

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Osimertinib and Therapeutic Conventional Surgery in people with Stage I Non-Small Cell Lung Cancer and Stage IA Non-Small Cell Lung Cancer, run by University of California, San Francisco at 3 sites in United States.

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 47 inclusion and 25 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: under way, not looking for participants, as of the sponsor's last update on 30 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Percentage of Participants With a Major Pathological Response (MPR) (time frame: Up to 1 year). 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 NCT03433469, which also lists 1 linked publication.

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 30 Mar 2026.

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