Status:

UNKNOWN

Study of AZD9291 in NSCLC Patients Harboring T790M Mutation Who Failed EGFR TKI and With Brain and/or LMS

Lead Sponsor:

Samsung Medical Center

Conditions:

Non-Small Cell Lung Cancer With EGFR T790M Mutation

With Brain and/or Leptomeningeal Metastasis

Eligibility:

All Genders

18+ years

Phase:

PHASE2

Brief Summary

AZD9291 is an oral potent irreversible EGFR TKI selective for sensitizing EGFR mutation and T790M resistance mutation but sparing wild-type EGFR. Preclinical studies indicate that AZD9291 has signific...

Detailed Description

1. Primary end points * Overall response rate (ORR) in CNS -brain metastasis cohort * Overall survival - Leptomeningeal with or without brain metastasis cohort 2. Secondary end points * Who...

Eligibility Criteria

Inclusion

  • EGFR activating mutant NSCLC patients who failed EGFR TKIs (gefitinib, erlotinib, or afatinib) and develop CNS disease (BM and/or LM) with T790M mutation either tissue or plasma. For patients with intracranial progression, prior radiation therapy is not mandatory. Extracranial progression is allowed.
  • Patients who failed to 3rd generation EGFR TKIs (AZD9291 (80mg), Rociletinib, HM61713) and develop CNS progression but stable extracranial disease
  • Age ≥18 years
  • ECOG performance status of 0 to 2
  • For BM, at least one measurable intracranial lesion as ≥ 10mm in the longest diameter by magnetic resonance imaging (MRI)
  • For LM, at least one site of CNS leptomeningeal disease that can be assessed by MRI
  • Adequate organ function as evidenced by the following;
  • Absolute neutrophil count \> 1.5 x 109/L;
  • platelets \> 100 x 109/L;
  • total bilirubin ≤1.5 UNL;
  • AST and/or ALT \< 5 UNL;
  • CCr ≥ 50mL/min.
  • Female subjects must either be of non-reproductive potential
  • Subject is willing and able to comply with the protocol
  • Signed written informed consent

Exclusion

  • Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 1 week
  • Any unresolved toxicities from prior therapy, greater than CTCAE grade 1
  • Mean QT interval corrected for heart rate (QTc) ≥ 470 ms
  • Uncontrolled systemic illness including uncontrolled hypertension, active bleeding, or active infection.
  • Past medical history of interstitial lung disease, drug induced interstitial lung disease, radiation pneumonitis which required steroid treatment
  • History of hypersensitivity to AZD9291
  • Known intracranial haemorrahge which is unrelated to tumor Refractory nausea and vomiting

Key Trial Info

Start Date :

May 8 2017

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

December 31 2021

Estimated Enrollment :

80 Patients enrolled

Trial Details

Trial ID

NCT03257124

Start Date

May 8 2017

End Date

December 31 2021

Last Update

August 16 2021

Active Locations (1)

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1

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

Seoul, South Korea, 135-710