| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Locally advanced or metastatic non-small cell lung cancer, not amenable to curative surgery or radiotherapy |
|
| E.1.1.1 | Medical condition in easily understood language |
| Specific type of lung cancer called "non-small cell lung cancer" (NSCLC) |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10029521 |
| E.1.2 | Term | Non-small cell lung cancer stage IIIB |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025055 |
| E.1.2 | Term | Lung cancer non-small cell stage IV |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To assess the efficacy of single agent AZD9291 compared with standard of care (SoC) Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) therapy as measured by progression free survival (PFS) |
|
| E.2.2 | Secondary objectives of the trial |
1) To assess the efficacy of AZD9291 compared with SoC EGFR-TKI therapy by assessment of PFS in patients with:
- Positive (or negative) pre-treatment T790M (amino acid substitution at position 790 in EGFR, from a threonine to a methionine) mutation.
- EGFR Ex19del or L858R mutation.
- EGFRm+ (Ex19del or L858R) detectable in plasma-derived circulating tumour deoxyribonucleic acid (ctDNA).
2) To further assess the efficacy of AZD9291 compared with SoC EGFR-TKI therapy by ORR, DoR, DCR, Depth of response and Overall survival (OS)
3) To characterise the pharmacokinetics (PK) of AZD9291 and its metabolites (AZ5104 and AZ7550).
4) To assess the impact of AZD9291 compared to SoC EGFR-TKI therapy on patients’ disease-related symptoms and Health Related Quality of Life (HRQoL).
5) To assess patient satisfaction with treatment when receiving AZD9291 compared with SoC EGFR-TKI therapy.
6) To assess the safety and tolerability profile of AZD9291 compared with SoC EGFR-TKI therapy. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 advanced NSCLC and eligible to receive first-line treatment with gefitinib or erlotinib as selected by the participating centre.
|
|
| E.4 | Principal exclusion criteria |
1. Treatment with any of the following:
• Prior treatment with any systemic anti-cancer therapy for advanced 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 inhibitors or inducers of cytochrome P450 (CYP) 3A4.
• 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 systemic treatment within 2 years of first dose of study drug.
3. Spinal cord compression, symptomatic and unstable brain metastases, requiring steroids over the last 4 weeks prior to randomisation in this study.
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 QTc value.
• Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG.
• 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.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression Free Survival (PFS) using investigator assessments according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| At baseline and every 6 weeks from randomization until progression |
|
| E.5.2 | Secondary end point(s) |
1) Analysis of OS (Overall Survival) (key secondary endpoint)
2) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 items (EORTC QLQ-C30) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Lung Cancer 13 items (EORTC QLQ-LC13).
EORTC QLQ-C30:
Questionnaire consisting of 30 items measuring subjects general cancer symptoms and functioning.
EORTC QLQ-LC13:
A complementary questionnaire measuring lung cancer symptoms and side effects from conventional chemo- and radiotherapy.
3) ORR (Objective Response Rate), Duration of Response (DoR), Disease Control Rate (DCR), Depth of response using investigator assessments according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1).
4) PK exposure parameters derived from plasma concentrations of AZD9291 and metabolites AZ5104 and AZ7550
Pharmacokinetics data from this study will be analysed using a population PK approach and may also form part of a pooled analysis with other AZD9291 studies; results from these analyses will be reported separately from the CSR
5) Assessing of patient satisfaction using Cancer Therapy Satisfaction Questionnaire 16 items (CTSQ-16)
6) Safety and tolerability endpoints assessed by number and severity of adverse events, clinical chemistry, haematology, urinalysis, vital signs, physical examination, body weight, digital electrocardiogram (ECG), left Ventricular Ejection Fraction (LVEF), World Health Organization (WHO) Performance Status and Ophthalmologic assessment
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| AZD9291 versus a standard of care Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 63 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Belgium |
| Brazil |
| Bulgaria |
| Canada |
| China |
| Czech Republic |
| France |
| Germany |
| Hong Kong |
| Hungary |
| Israel |
| Italy |
| Japan |
| Korea, Republic of |
| Philippines |
| Poland |
| Romania |
| Russian Federation |
| Spain |
| Sweden |
| Taiwan |
| Thailand |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The last visit of the last patient undergoing the study |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
