AZD9291 versus Platinum-Based Doublet-Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer

• Register: EUCTR
• Last refreshed on: 8 January 2024
• Main ID: EUCTR2014-000594-39-NL
• Date of registration: 15/07/2014
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: AZD9291 versus Platinum-Based Doublet-Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer
• Scientific title: A Phase III, Open Label, Randomized Study of AZD9291 versus Platinum-Based Doublet Chemotherapy for Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer whose Disease has Progressed with Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and whose Tumours harbour a T790M mutation within the Epidermal Growth Factor Receptor Gene (AURA3) - AURA3
• Date of first enrolment: 06/08/2014
• Target sample size: 610
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000594-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: yes Other specify the comparator: platinum-based doublet chemotherapy Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Canada, China, European Union, France, Germany, Hong Kong, Hungary, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Sweden, Taiwan, United Kingdom, United States

Contacts

• Name: Information Center
• Affiliation: AstraZeneca

• Name: Information Center
• Affiliation: AstraZeneca

Key inclusion & exclusion criteria

Inclusion criteria:
- Subjects with histologically- or cytologically-documented NSCLC.
- Locally advanced or metastatic NSCLC.
- Radiological documentation of disease progression following 1st line EGFR TKI Treatment without any further treatment.
- Eligible to receive treatment with the selected doublet-chemotherapy.
- Confirmation of EGFR mutation.
- Central confirmation of T790M+ mutation status.
- World Health Organisation (WHO) performance status 0-1.
- At least one lesion, not previously irradiated.
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 400
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 210

Exclusion criteria:
- Treatment with more than one prior line of treatment for advanced NSCLC.
- Treatment with an approved EGFR-TKI (eg, erlotinib, gefitinib, afatinib) within 8 days or approximately 5 x half-life of the first dose of study treatment.
- Any investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment.
- Previous treatment with an unapproved EGFR-TKI.
- Prior neo-adjuvant or adjuvant chemotherapy treatment within 6 months of
starting 1st EGFR TKI treatment


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Locally Advanced or Metastatic Non-Small Cell Lung Cancer where Disease has Progressed with Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and where Tumours harbour a T790M mutation within the Epidermal Growth Factor Receptor Gene
MedDRA version: 17.1 Level: PT Classification code 10029515 Term: Non-small cell lung cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: AZD9291 80 mg film-coated tablet
Product Code: AZD9291
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Not yet assigned
CAS Number: 1421373-66-1
Current Sponsor code: AZD9291 mesylate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 80-

Product Name: AZD9291 40 mg film-coated tablet
Product Code: AZD9291
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Not yet assigned
CAS Number: 1421373-66-1
Current Sponsor code: AZD9291 mesylate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Product Name: Carboplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Carboplatin
Other descriptive name: CARBOPLATIN

Product Name: Cisplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: cisplatin
Other descriptive name: CISPLATIN

Product Name: Pemetrexed
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: PEMETREXED
Other descriptive name: PEMETREXED

Primary Outcome(s)

Secondary Objective: To further assess the efficacy of AZD9291 compared with platinum-based doublet chemotherapy in terms of:
- Objective Response Rate (ORR)
- Duration of Response (DoR)
- Disease Control Rate (DCR)
- Overall Survival (OS)
- Tumour shrinkage

To assess the effect of AZD9291 compared to platinum-based doublet chemotherapy on subjects’ disease-related symptoms and health related quality of life (HRQoL).

To characterise the pharmacokinetics (PK) of AZD9291, AZ5104 and AZ7550 in subjects receiving AZD9291.

Safety Objective

Main Objective: To assess the efficacy of AZD9291 compared with platinum-based doublet chemotherapy by assessment of Progression Free Survival (PFS)

Timepoint(s) of evaluation of this end point: At baseline and every 6 weeks from randomization until progression.

Primary end point(s): Progression Free Survival (PFS) using investigator assessments according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1).

Secondary Outcome(s)

Secondary end point(s): ORR, DoR, DCR and tumour shrinkage using investigator assessments according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1).

Analysis of overall survival.
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.

PK exposure parameters derived from plasma concentrations of AZD9291, and metabolites AZ5104 and AZ7550.
PK Parameters (such as Clss/F, Css, min and Css, max AUCss) will be derived using population PK analysis and reported separately to the CSR. Data from this study may form part of a pooled analysis with data from other studies.

Safety endpoints:
- Adverse events (graded by Common Terminology Criteria for Adverse Event (CTCAE v4)
- Clinical chemistry, haematology and urinalysis
- Vital signs (pulse and blood pressure), Physical Examination, Weight
- Centrally reviewed digital Electrocardiogram (ECG)
- Echocardiogram/ Multi Gated Acquisition Scan (MUGA) (for Left Ventricular Ejection Fraction)
- World Health Organization (WHO) performance status

Timepoint(s) of evaluation of this end point: At baseline and every 6 weeks from randomization until progression.

Secondary ID(s)

2014-000594-39-DE

D5160C00003

NCT02151981

Source(s) of Monetary Support

AstraZeneca AB

Ethics review

Status: Approved
Approval date: 06/08/2014
Contact: