Intracranial Activity of AZD9291 (TAGRISSO) in Advanced EGFRm NSCLC Patients With Asymptomatic Brain Metastases

NCT02736513 | Unknown Phase 2

• 1 other identifier: ESR-15-11084
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Patients will receive AZD9291 at a dose of 80 mg once daily. Intracranial response will be assessed with brain MRI scan, systemic evaluation will be done by PET-CT (Positron Emission Tomography-Computed Tomography) scan. In case of isolated CNS progression which may or may not be accompanied by asymptomatic systemic progression, AZD9291 dose will be escalated to 160 mg once daily. For patients whose intracranial disease will progress further, brain radiotherapy (in the form of SRS or WBRT) will be administered; treatment with AZD9291 will be interrupted and re-initiated at a standard dose after the end of radiotherapy course in the absence of symptomatic systemic progression. The treatment will be continued until symptomatic systemic progression, unacceptable toxicity or further intracranial progression following brain radiotherapy administration (whichever occurs first). All patients will be followed until death or 5 years.

Conditions

Lung Cancer

Keywords

Tagrisso; AZD9291; EGFRm; brain metastases; NSCLC

Outcome Measures

Primary Outcomes (1)

• Intracranial overall response rate as defined by modified RECIST

  Patients will receive TAGRISSO. Intracranial response will be assessed with brain MRI scan, systemic evaluation will be done by PET-CT scan.

  5 years

Secondary Outcomes (3)

• Intracranial disease control rate (IDCR) as defined by mRECIST

  5 years

• median time to intracranial response (mTTIR) as defined by mRECIST

  5 years

• median intracranial progression free survival (mIPFS) as defined by mRECIST

  5 years

Study Arms (3)

AZD9291 80 mg - naive patients

EXPERIMENTAL

naive patients with tumors harbouring either exon 19 deletion, L858R, T790M, or uncommon sensitizing EGFR mutations, will be treated with AZD9291 80 mg/day

Drug: AZD9291

AZD9291 80 mg - previously treated T790M was diagnosed

EXPERIMENTAL

Patients previously treated with first and second generation EFGR TKIs (either Gefitinib, Erlotinib or Afatinib) in whom T790Mwas diagnosed either in the tumor specimen or in the ctDNA after testing it following the most recent disease progression, will be treated with AZD9291 80 mg/day

Drug: AZD9291

AZD9291 80 mg - previously treated unrelated to T790M

EXPERIMENTAL

patients advanced NSCLC previously treated with 1st/2nd generation EGFR TKIs (either gefitinib. erlotinib or afatinib) who progressed unrelated to T790M (T790M-). No restriction regarding the number of prior EGFR TKIs or cytotoxic chemotherapy lines of treatment is applied.

Drug: AZD9291

Interventions

AZD9291 DRUG

Patients will receive AZD9291 at a dose of 80 mg once daily.

Also known as: TAGRISSO

AZD9291 80 mg - naive patients; AZD9291 80 mg - previously treated T790M was diagnosed; AZD9291 80 mg - previously treated unrelated to T790M

Eligibility Criteria

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

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both sponsor staff and/or staff at the study site).
• Previous treatment with AZD9291.
• Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inhibitors of CYP3A4 (at least 1 week prior) and potent inducers of CYP3A4 (at least 3 week prior) (Appendix A). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer/inhibitory effects on CYP3A4.
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the exception of alopecia and grade 2, prior platinum-therapy related neuropathy.
• EGFR TKI - resistant EGFR mutations (e.g., insertion in exon 20).
• T790M is allowed.
• Patients previously treated with WBRT.
• Pregnant or lactating women.
• Inability to sign the informed consent form.
• Any concurrent and/or other active malignancy that has required systemic treatment within 2 years of first dose of study drug.
• 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.
• Inability to swallow the formulated product, malabsorption syndrome, refractory nausea and vomiting that would preclude adequate absorption of AZD9291.
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (QTc) \>470 msec, obtained from 3 consequent ECGs, using the screening clinic ECG machine-derived QTc value;
• Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG;

Sponsors & Collaborators

• Soroka University Medical Center: lead

Study Sites (1)

Shaare Zedek

Jerusalem, Israel

Location

Related Publications (1)

• Peled N, Kian W, Inbar E, Goldstein IM, Zemel M, Rotem O, Rozenblum AB, Nechushtan H, Dudnik E, Levin D, Zer A, Keren-Rosenberg S, Yust-Katz S, Fuchs V, Remilah AA, Shelef I, Roisman LC. Osimertinib in advanced EGFR-mutant lung adenocarcinoma with asymptomatic brain metastases: an open-label, 3-arm, phase II pilot study. Neurooncol Adv. 2021 Dec 27;4(1):vdab188. doi: 10.1093/noajnl/vdab188. eCollection 2022 Jan-Dec.

  PMID: 35156036 DERIVED

MeSH Terms

Conditions

Lung Neoplasms; Brain Neoplasms

Interventions

osimertinib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Nir Peled, MD PhD FCCP

  Shaare Zedek Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Oncology

Study Record Dates

• First Submitted: March 22, 2016
• First Posted: April 13, 2016
• Study Start: May 1, 2016
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: September 2, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will share

Locations

IL (1)