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

NCT03433469 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 2 other identifiers: 17658NCI-2018-00019
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Stage I Non-Small Cell Lung Cancer; Stage IA Non-Small Cell Lung Cancer; Stage IB Non-Small Cell Lung Cancer; Stage II Non-Small Cell Lung Cancer; Stage IIA Non-Small Cell Lung Cancer; Stage IIB Non-Small Cell Lung Cancer; Stage IIIA Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (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.

  Up to 1 year

Secondary Outcomes (9)

• Objective Response Rates (ORR)

  Up to 70 days

• Mean Disease-free Survival (DFS)

  Up to 5 years

• Disease-free Survival Rate (DFS)

  Up to 5 years

• Overall Survival (OS)

  Up to 5 years

• Median Percentage Change in Tumor Burden (Depth of Response)

  Up to 1 year

Study Arms (1)

Treatment (osimertinib)

EXPERIMENTAL

Participants 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.

Drug: Osimertinib; Procedure: Therapeutic Conventional Surgery

Interventions

Osimertinib DRUG

Given PO (orally)

Also known as: AZD-9291, Tagrisso

Treatment (osimertinib)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgery

Treatment (osimertinib)

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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:

Sponsors & Collaborators

• AstraZeneca: collaborator
• University of California, San Francisco: lead

Study Sites (3)

University of California, Davis

Davis, California, 95864, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Related Publications (1)

• 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.

  PMID: 39028931 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Dr. Collin M. Blakely, MD, PhD
• Organization: University of California, San Francisco

collin.blakely@ucsf.edu

(415) 502-6959

Study Officials

• Collin Blakely, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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 25, 2018
• First Posted: February 14, 2018
• Study Start: July 31, 2018
• Primary Completion: January 31, 2023
• Study Completion (Estimated): September 30, 2027
• Last Updated: March 30, 2026
• Results First Posted: January 18, 2024

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)