Uncommon EGFR AZD9291

NCT03424759 | Unknown Phase 2

• 1 other identifier: 2015-06-176
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

EGFR (ErbB1) mutations define a lung cancer subtype with exquisite sensitivity to EGFR tyrosine kinase inhibitors (TKIs). While in-frame deletion in exon 19 (Del19) and a point mutation (L858R) in exon 21 are the two most common sensitizing EGFR mutations in NSCLC, approximately 10% of EGFR mutation-positive tumors harbor uncommon mutations. These mutations represent a heterogeneous group of rare molecular alterations (or combinations) within exons 18-21, whose oncogenicity and sensitivity to EGFR TKIs may vary and has not been prospectively studied. Recently, a retrospective analysis reported that overall response rate of EGFR TKI (gefitinib or erlotinib) treatment was about 10% or less in Korean NSCLC patients with uncommon EGFR mutation other than del19, L858R and T790M \[11\]. In preclinical data, the potency of AZD9291 against uncommon EGFR mutants other than exon 20 insertion mutation was fairly good. Based on the result, in this study, we try to evaluate the efficacy of AZD9291, the potent irreversible inhibitor, in NSCLC patients with harboring uncommon EGFR mutations.

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  30%

  through study completion, an average of 2 years

Study Arms (1)

AZD9291

EXPERIMENTAL

Patients will be treated 80 mg/day of AZD9291 orally (1 cycle for 21 days).

Drug: AZD9291

Interventions

AZD9291 DRUG

Patients will be treated 80 mg/day of AZD9291 orally (1 cycle for 21 days).

AZD9291

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed metastatic or recurrent stage IV NSCLC with activating EGFR mutation other than deletion in exon 19, L858R, T790M and insertion in exon 20
• metastatic or recurrent NSCLC
• Be 19years of age on day of signing informed consent
• ECOG performance status of 0 to 2
• At least one measurable lesion by RECIST 1.1(The part of radiation treatment in the palliative setting is excluded.)
• Untreated asymptomatic brain metastasis or symptomatic brain metastasis treated with local treatment such as operation, whole brain radiotherapy, or gamma-knife surgery
• At least 2 weeks later after whole brain radiotherapy or at least 4 weeks later after palliative thoracic radiotherapy
• Adequate organ function as evidenced by the following; Absolute neutrophil count \> 1.5 x 109/L; Hb \> 9.0g/dL; platelets \> 100 x 109/L; total bilirubin ≤1.5 UNL; AST and/or ALT \< 2.5 ULN if no demonstrable liver metastases or \< 5 UNL in the presence of liver metastases, CCr ≥ 50mL/min
• Written informed consent form

You may not qualify if:

• Prior treatment with EGFR TKI
• Major surgery undertaken less than 4 weeks before the study
• Localized palliative radiotherapy unless completed more than 2 weeks before the study
• Uncontrolled systemic illness such as DM, CHF, unstable angina, hypertension or arrhythmia
• Pregnant or nursing women (Women of reproductive potential have to agree to use an adequate contraceptive method)
• Uncontrolled symptomatic brain metastasis
• Prior history of malignancy within 5 years from study entry except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer, or well-treated thyroid cancer
• Concomitant use of CYP3A4 inducers/inhibitors
• Prolonged QT interval in ECG (QTc \>450 msec)
• Prior history of interstitial lung disease

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (1)

Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine

Seoul, 135-710, South Korea

Location

Related Publications (1)

• Cho JH, Lim SH, An HJ, Kim KH, Park KU, Kang EJ, Choi YH, Ahn MS, Lee MH, Sun JM, Lee SH, Ahn JS, Park K, Ahn MJ. Osimertinib for Patients With Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Multicenter, Open-Label, Phase II Trial (KCSG-LU15-09). J Clin Oncol. 2020 Feb 10;38(5):488-495. doi: 10.1200/JCO.19.00931. Epub 2019 Dec 11.

  PMID: 31825714 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

Study Officials

• Myung-Ju Ahn

  Samsung Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 9, 2018
• First Posted: February 7, 2018
• Study Start: January 1, 2016
• Primary Completion: December 31, 2017
• Study Completion: July 31, 2019
• Last Updated: February 7, 2018

Record last verified: 2018-02

Locations

KR (1)