A late stage clinical trial to investigate the efficacy and safety of AZD9291 versus Gefitinib or Erlotinib in patients with locally advanced or metastatic Non-Small Cell Lung Cancer

Phase 1

• Conditions: ocally advanced or metastatic non-small cell lung cancer, not amenable to curative surgery or radiotherapy; MedDRA version: 20.0Level: PTClassification code 10029521Term: Non-small cell lung cancer stage IIIBSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10025055Term: Lung cancer non-small cell stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-002694-11-HU
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-10-18
• Last Update Posted: 10 August 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 530

Inclusion Criteria

1. Male or female, aged at least 18 years.
2. Pathologically confirmed adenocarcinoma of the lung.
3. Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy.
4. The tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R).
5. Mandatory provision of an unstained, archived tumour tissue sample in a quantity sufficient to allow for central analysis of EGFR mutation status.
6. Patients must be treatment-naïve for locally advanced or metastatic NSCLC and eligible to receive first-line treatment with gefitinib or erlotinib as selected by the participating centre. Prior adjuvant and neo-adjuvant therapy is permitted (chemotherapy, radiotherapy, investigational agents)
7. Provision of informed consent prior to any study specific procedures,
sampling, and analysis.
8. World Health Organization Performance Status of 0 to 1 with no
clinically significant deterioration over the previous 2 weeks and a
minimum life expectancy of 12 weeks.
9. At least one lesion, not previously irradiated and not chosen for biopsy
during the study Screening period, that can be accurately measured at
baseline as =10 mm in the longest diameter (except lymph nodes which
must have a short axis of =15 mm) with computerized tomography (CT)
or magnetic resonance imaging (MRI), and which is suitable for accurate
repeated measurements.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 350
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 180

Exclusion Criteria

1. Treatment with any of the following:
• Prior treatment with any systemic anti-cancer therapy for locally advanced / metastatic NSCLC.
• Prior treatment with an EGFR-TKI.
• Major surgery within 4 weeks of the first dose of study drug.
• Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug.
• Patients currently receiving medications or herbal supplements known to be potent inducers of cytochrome P450 (CYP) 3A4.
• Alternative anti-cancer treatment
• Treatment with an investigational drug within five half-lives of the compound or any of its related material.
2. Any concurrent and/or other active malignancy that has required treatment within 2 years of first dose of study drug.
3. Spinal cord compression, symptomatic and unstable brain metastases, except for those patients who have completed definitive therapy, are not on steroids, have a stable neurologic status for at least 2 weeks after completion of the definitive therapy and steroids.
4. 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).
5. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of AZD9291.
6. Any of the following cardiac criteria:
• Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs, using the screening clinic ECG machine-derived QTcF value.
• Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG.
• Any patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval.
7. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
8. Involvement in the planning and/or conduct of the study

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified