Neo-adjuvant Trial With AZD9291 in EGFRm+ Stage IIIA/B NSCLC

Lung Cancer, Non-small Cell Clinical Trial

Official title:

Neo-adjuvant Trial With AZD9291 in EGFRm+ Stage IIIA/B NSCLC - a Phase 2 Open-label Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02824952
• Other study ID #: 0432-20-SZMC
• Secondary ID: 0432-20-SZMC
• Status: Recruiting
• Phase: Phase 2
• Start date: November 1, 2018
• Est. completion date: December 2022

Study information

• Verified date: November 2021
• Source: Shaare Zedek Medical Center
• Contact: Nir Peled, MD PhD FCCP
• Phone: +972 0 587040620
• Email: nirp[@]szmc.org.il
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients will receive AZD9291 at a dose of 80 mg once daily. Systemic evaluation will be done by PET-CT scan after 6 weeks.

In responding patients AZD9291 will be given orally 80 mg daily for 12 weeks. Non-responding patients will receive AZD9291 for the period of 6 or 12 weeks (according to the results of response assessment at each time-point).

Description:

Patients will receive AZD9291 at a dose of 80 mg once daily. Systemic evaluation will be done by PET-CT scan after 6 weeks.

In responding patients AZD9291 will be given orally 80 mg daily for 12 weeks. Non-responding patients will receive AZD9291 for the period of 6 or 12 weeks (according to the results of response assessment at each time-point). All the patients will be followed for 2 years.

The imaging modality used for RECIST v1.1 assessments will be PET-CT scan.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 2022
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria.

1. Provision of informed consent prior to any study specific procedures

2. Male or female, aged at least 18 years.

3. Treatment-naïve stage IIIA/B NSCLC with an activating sensitizing EGFR mutation/T790M

• Uncommon sensitizing EGFR mutations are allowed.

4. Measurable disease by RECIST criteria v1.1.

5. Patients are amenable for curative chemo-radiotherapy.

6. ECOG PS 0/1.

•total bilirubin less then 1.5 mg/dL, ALT+ AST levels 3 times above the upper normal limit.

7. Normal hematologic, renal and liver function:

• Absolute neutrophil count over 1500/mm3, platelets over 100,000/mm3, hemoglobin over 9 g/dL;

• Creatinine concentration less than 1 mg/dL, or creatinine clearance over 60 mL/min;

• Total bilirubin less than 1.5 mg/dL, ALT and AST levels 3 times above the upper normal limit.

8. FEV-1 more than1 liter.

9. Female patients with reproductive potential must have a negative pregnancy test (serum/urine) prior to starting treatment.

10. All patients with reproductive potential must agree to use barrier contraception methods while receiving the study treatment.

Exclusion criteria

1. EGFR TKI - resistant EGFR mutations (e.g., insertion in exon 20)

2. T790M is allowed.

3. Treatment with any of the following:

4. Prior treatment with any systemic anti-cancer therapy for advanced NSCLC;

5. Prior treatment with an EGFR-TKI;

6. Major surgery within 4 weeks of the first dose of study drug;

7. Treatment with an investigational drug within five half-lives of the compound.

8. Pregnant or lactating women.

9. Inability to sign the informed consent form.

10. Any concurrent and/or other active malignancy that has required systemic treatment within 2 years of first dose of study drug.

11. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV), uncontrolled diabetes.

12. Inability to swallow the formulated product, malabsorption syndrome, refractory nausea and vomiting that would preclude adequate absorption of AZD9291.

13. Any of the following cardiac criteria:

14. Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 consequent ECGs, using the screening clinic ECG machine-derived QTc value;

15. Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG;

16. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, including unexplained sudden death under 40 years of age in a first-degree relative, or any concomitant medication known to prolong the QTc interval.

17. Any evidence/past medical history of interstitial lung disease (ILD) or radiation pneumonitis which required steroid treatment.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer, Non-small Cell

Intervention

Drug:
• Tagrisso
taking orally everyday for 6 or 12 weeks.

Locations

Country	Name	City	State
Israel	Shaare Zedek Medical Center	Jerusalem

Sponsors (2)

Lead Sponsor	Collaborator
Shaare Zedek Medical Center	AstraZeneca

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate as defined by RECIST 1.1	assessed by PET-CT	12 weeks
Secondary	mPFS measured by Kaplan-Meier method.	mPFS measured by Kaplan-Meier method.	2 years
Secondary	Comparing GTV (Gross tumor volume) before and after the neoadjuvant therapy	Comparing GTV (Gross tumor volume) before and after the neoadjuvant therapy	2 years