Osimertinib, Surgery, and Radiation Therapy in Treating Patients With Stage IIIB or IV Non-small Cell Lung Cancer With EGFR Mutations, NORTHSTAR Study

NCT03410043 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2017-0228NCI-2018-00937
• Study Type: interventional
• Target: 173
• Locations: 1 country
• Sites: 4

Brief Summary

This phase II trial studies how well osimertinib, surgery, and radiation therapy work in treating patients with stage IIIB or IV non-small cell lung cancer with EGFR mutations. Osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving osimertinib, surgery, and radiation therapy may work better at treating non-small cell lung cancer with EGFR mutations.

Conditions

Lung Non-Small Cell Carcinoma; Recurrent Lung Non-Small Cell Carcinoma; Stage IIIB Lung Cancer AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  Will be estimated using Kaplan-Meier method. The stratified log-rank test will be performed to test the difference in time-to-event distributions between treatment groups. Stratified Cox proportional hazards model will be utilized to include multiple covariates in the time-to-event analysis and to estimate hazard ratios.

  From the start date of osimertinib assessed up to 4 years

Secondary Outcomes (5)

• Overall survival

  From the treatment start date assessed up to 4 years

• Time to progression of target lesions

  Up to 4 years

• Time to appearance of new metastases

  Up to 4 years

• PFS in oligometastatic subgroup

  Up to 4 years

• Incidence of adverse events

  Up to 30 days post treatment

Study Arms (2)

Group I (LCT)

EXPERIMENTAL

Patients receive osimertinib PO QD for 6-12 weeks. Patients then undergo surgery and/or radiation therapy daily for 5 consecutive days every week for up to 8 weeks. Patients continue osimertinib during and after radiation therapy. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Osimertinib; Radiation: Radiation Therapy; Procedure: Therapeutic Conventional Surgery

Group II (no LCT)

EXPERIMENTAL

Patients receive osimertinib PO QD. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Osimertinib

Interventions

Therapeutic Conventional Surgery PROCEDURE

Undergo surgery

Group I (LCT)

Osimertinib DRUG

Given PO

Also known as: AZD-9291, AZD9291, Mereletinib, Tagrisso

Group I (LCT); Group II (no LCT)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Group I (LCT)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed non-small cell lung cancer
• Stage IIIB/IV or recurrent non-small cell lung cancer which is not amenable to curative intent therapy
• Patients must have one of the following:
• NSCLC which harbors EGFR exon 19 deletion or L858R mutation. This subset of patients must be TKI naive; OR
• NSCLC which harbors an EGFR T790M mutation that was acquired following progression on erlotinib, gefitinib or afatinib. This subset of patients must have not received prior third generation TKI
• NOTE: EGFR mutation must be documented by a Clinical Laboratory Improvement Amendments (CLIA) certified test
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Candidate for local consolidation therapy to at least one site of disease
• Signed and dated written informed consent prior to admission to the study in accordance with International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH)-Good Clinical Practice (GCP) guidelines and to the local legislation
• Ability to take pills by mouth
• Females of childbearing potential:
• Must not be breast feeding
• Must have a negative serum or urine pregnancy test
• Must agree to use adequate contraception for a minimum of two weeks prior to receiving study medication until 3 months after discontinuation of the study medication

You may not qualify if:

• Previous treatment with osimertinib, or a 3rd generation EGFR TKI. NOTE: Patients who are receiving initial osimertinib (6-12 weeks) outside this study are not excluded
• Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of CYP3A4 (at least 3 week prior). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4
• Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 (with the exception of alopecia grade 2) at the time of starting study treatment
• 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 subject to participate in the trial or which would jeopardize compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required
• 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
• Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
• Males and females of reproductive potential who are not using and effective method of birth control and females who are pregnant or breastfeeding or have a positive (urine or serum) pregnancy test prior to study entry
• History of hypersensitivity of osimertinib (or active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib)
• Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirement
• Absolute neutrophil count \< 1,500/mcL
• Platelet \< 100,000/mcL
• Hemoglobin \< 9.0 g/dL
• Total bilirubin \> 1.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or \> 3 times ULN in the presence of documented Gilbert's syndrome or liver metastases
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \> 2.5 times ULN or \> 5 times ULN if liver metastases are present

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• National Comprehensive Cancer Network: collaborator

Study Sites (4)

UCSF Medical Center-Mount Zion

San Francisco, California, 94115, United States

Location

University of Colorado

Denver, Colorado, 80217-3364, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

osimertinib; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena

Study Officials

• Saumil Gandhi

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 18, 2018
• First Posted: January 25, 2018
• Study Start: January 17, 2018
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: December 26, 2025

Record last verified: 2025-12

Locations

US (4)