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Uncommon EGFR AZD9291

Primary Purpose

Non Small Cell Lung Cancer

Status

Unknown status

Phase

Phase 2

Locations

Korea, Republic of

Study Type

Interventional

Intervention

AZD9291

About this trial

This is an interventional treatment trial for Non Small Cell Lung Cancer

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AZD9291

Arm Description

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

Outcomes

Primary Outcome Measures

Objective response rate

30%

Secondary Outcome Measures

Full Information

NCT ID

NCT03424759

First Posted

January 9, 2018

Last Updated

February 5, 2018

Sponsor

Samsung Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT03424759

Brief Title

Uncommon EGFR AZD9291

Official Title

An Open Label, Multicenter, Phase II Single-arm Trial of AZD9291 in Non-small Cell Lung Cancer (NSCLC) Patients With Uncommon Epidermal Growth Factor Receptor Mutations

Study Type

Interventional

2. Study Status

Record Verification Date

February 2018

Overall Recruitment Status

Unknown status

Study Start Date

January 1, 2016 (Actual)

Primary Completion Date

December 31, 2017 (Actual)

Study Completion Date

July 31, 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Samsung Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

Detailed Description

This is a single-arm phase II trial to evaluate the efficacy of AZD9291 (experimental) NSCLC patients with uncommon EGFR mutation. The primary endpoint of the study is objective response rate. 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 (9). In this study, we expect an objective response rate of about 30% for the experimental arm (AZD9291 therapy) compared to that of about 10% in the historical control based on previous studies. A sample size of 33 efficacy-evaluable patients would provide a power of 90% for testing the null hypothesis of 10% ORR vs. alternative hypothesis of 30% using a single-arm exact binomial test with a 1=sided significance level of 5%. The experimental therapy will be rejected if 6 or fewer patients out of 33 respond. Allowing for a follow-up loss rate of 10%, the total sample size is 37 patients. Patients will be treated 80 mg/day of AZD9291 orally (1 cycle for 21 days). Subjects (with the exception of subjects with insulin dependent diabetes) must fast for ≥1 hours prior to taking a dose to ≥2 hour post dose. Water is permitted during this fasting period. Cycles were repeated until disease progression, unacceptable toxicity, or until the patient or the investigator requested therapy discontinuation. If the efficacy will be proven, the patient could receive the treatment continuously.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non Small Cell Lung Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

37 (Actual)

8. Arms, Groups, and Interventions

Arm Title

AZD9291

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

AZD9291

Intervention Description

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

Primary Outcome Measure Information:

Title

Objective response rate

Description

30%

Time Frame

through study completion, an average of 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

19 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Myung-Ju Ahn

Organizational Affiliation

Samsung Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

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

City

Seoul

ZIP/Postal Code

135-710

Country

Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

31825714

Citation

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.

Results Reference

derived

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Uncommon EGFR AZD9291

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