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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Lung Cancer, Non-small Cell
• Intervention / Treatment: Drug: Tagrisso

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Nir Peled, MD PhD FCCP; Phone Number: +972 0 587040620; Email: nirp@szmc.org.il

Study Locations

• Israel
  • Jerusalem, Israel
    • Recruiting
    • Shaare Zedek Medical Center
    • Contact: Nir Peled, MD PhD FCCP; Email: nirp@szmc.org.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tagrisso 80 mg; 80 mg of Tagrisso(AZD9291) will be given every day for 6 or 12 weeks.	Drug: Tagrisso; taking orally everyday for 6 or 12 weeks.; Other Names: AZD9291

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate as defined by RECIST 1.1	assessed by PET-CT	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mPFS measured by Kaplan-Meier method.	mPFS measured by Kaplan-Meier method.	2 years
Comparing GTV (Gross tumor volume) before and after the neoadjuvant therapy	Comparing GTV (Gross tumor volume) before and after the neoadjuvant therapy	2 years

Collaborators and Investigators

• Sponsor: Shaare Zedek Medical Center
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Nir Peled, MD PhD FCCP, Shaare Zedek Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: June 29, 2016
• First Submitted That Met QC Criteria: July 3, 2016
• First Posted (Estimate): July 7, 2016

Study Record Updates

• Last Update Posted (Actual): November 18, 2021
• Last Update Submitted That Met QC Criteria: November 10, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: NSCLC; Tagrisso; AZD9291; EGFRm
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Osimertinib
• Other Study ID Numbers: 0432-20-SZMC (Other Identifier: Shaare Zedek Medical Center)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No