NCT03410043

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

Randomized Phase II Trial of Osimertinib With or Without Local Consolidation Therapy (LCT) for Patients With EGFR-Mutant Metastatic NSCLC (NORTHSTAR)

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 173 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

PRIMARY OBJECTIVE: I. To determine whether, in patients with tyrosine kinase inhibitor (TKI) naive or TKI resistant (acquired T790M) metastatic EGFR mutant non-small cell lung cancer (NSCLC) who do not progress after 6-12 weeks of induction osimertinib, local consolidative therapy (LCT; radiotherapy +/- surgical resection) followed by osimertinib prolongs progression-free survival (PFS) compared with osimertinib alone. SECONDARY OBJECTIVES: I. To determine whether osimertinib plus LCT improves time to progression of non-irradiated lesions (TTP-NIL) and time to appearance of new metastases (TANM) compared with osimertinib alone. II. To determine whether osimertinib plus LCT improves the time to progression of target versus (vs.) non-target lesions compared with osimertinib alone. III. To determine whether osimertinib plus LCT improves progression-free survival compared with osimertinib alone in TKI naive EGFR (L8585R/exon 19 deletion) mutant metastatic NSCLC. IV. To determine whether osimertinib plus LCT improves progression-free survival compared with osimertinib alone in TKI resistant (acquired T790M) EGFR mutant NSCLC. V. To determine whether osimertinib plus LCT improves progression-free survival compared with osimertinib alone in the subgroup of patients with oligometastatic NSCLC (up to 3 metastases). VI. To assess the safety and tolerability of osimertinib with and without LCT. VII. To determine whether osimertinib plus LCT improves overall survival (OS) compared with osimertinib alone. VIII. To determine if there is a difference in survival outcomes or toxicity by radiation treatment modality (protons vs. photons). EXPLORATORY OBJECTIVES: I. To explore the association of baseline genomic, proteomic and gene expression profiles (from tumor, germline deoxyribonucleic acid \[DNA\], and cell free \[cf\]DNA) with clinical benefit and in patients treated with osimertinib with or without LCT. II. To determine modulation of genomic, proteomic and gene expression tumor profiles by induction osimertinib. III. To explore osimertinib resistance mechanisms. IV. To determine the immunomodulatory effects of osimertinib plus LCT. OUTLINE: Patients are randomized to 1 of 2 groups. GROUP I (LCT): Patients receive osimertinib orally (PO) once daily (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. GROUP II (NO LCT): Patients receive osimertinib PO QD. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up within 30 days, then every 6 months thereafter.

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

Interventions

Type	Name	Description
DRUG	Osimertinib	Given PO
RADIATION	Radiation Therapy	Undergo radiation therapy
PROCEDURE	Therapeutic Conventional Surgery	Undergo surgery

Timeline

• Start date: 2018-01-17
• Primary completion: 2027-04-01
• Completion: 2027-04-01
• First posted: 2018-01-25
• Last updated: 2026-04-06

Locations

4 sites across 1 country: United States

Regulatory

• FDA-regulated drug study