BIBW 2992 (Afatinib) Versus Chemotherapy as First Line Treatment in NSCLC With EGFR Mutation

Boehringer Ingelheim345 enrolled

Overview

This randomised, open label phase III trial will be performed in patients with adenocarcinoma of the lung with tumours harbouring an Epidermal Growth Factor Receptor activating mutation. The objectives of the trial are to compare the efficacy of single agent BIBW 2992, Arm A, with Pemetrexed/Cisplatin chemotherapy, Arm B, as first line treatment for this group of patients.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

345

Conditions

Carcinoma, Non-Small-Cell Lung Adenocarcinoma

Interventions

PemetrexedDRUG

Pemetrexed IV given once every 3 weeks for up to 6 cycles

BIBW 2992DRUG

BIBW 2992 once daily until progression

CisplatinDRUG

Cisplatin IV given once every 3 weeks for up to 6 cycles

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion criteria: * Pathologically confirmed diagnosis of Stage IIIB (with cytologically proven pleural effusion or pericardial effusion) or Stage IV adenocarcinoma of the lung. Patients with mixed histology are eligible if adenocarcinoma is the predominant histology. * Epidermal Growth Factor Receptor mutation detected by central laboratory analysis of tumour biopsy material. * Measurable disease according to RECIST 1.1. * Eastern Cooperative Oncology Group score of 0 or 1. * Age \>/= 18 years. * Life expectancy of at least three months. * Written informed consent that is consistent with International Conference on Harmonisation-Good Clinical Practice guidelines. Exclusion criteria: * Prior chemotherapy for relapsed and/or metastatic NSCLC. Neoadjuvant/adjuvant chemotherapy is permitted if at least 12 months has elapsed between the end of chemotherapy and randomisation. * Prior treatment with Epidermal Growth Factor Receptor targeting small molecules or antibodies. * Radiotherapy or surgery (other than biopsy) within 4 weeks prior to randomisation. * Active brain metastases * Any other current malignancy or malignancy diagnosed within the past five years * Known pre-existing interstitial lung disease. * Significant or recent acute gastrointestinal disorders with diarrhoea as a major symptom. * History or presence of clinically relevant cardiovascular abnormalities. * Any other concomitant serious illness or organ system dysfunction. * Adequate absolute neutrophil count and platelet count * Adequate liver and kidney function * Active hepatitis B infection, active hepatitis C infection or known HIV carrier.

Locations (133)

Outcomes

Primary Outcomes

Progression-Free Survival (PFS) Time

PFS was defined as time from randomisation to disease progression or death whichever occured first. Assessed by central independent review according to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1). Median time results from unstratified Kaplan-Meier estimates.

Time frame: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression

Secondary Outcomes

Percentage of Patients With Objective Response (OR)

OR was defined as Complete Response (CR) or Partial Response (PR). Assessed by central independent review according to RECIST 1.1.

Time frame: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression

Percentage of Participants With Disease Control (DC)

DC was defined as a patient with OR or Stable Disease (SD). Assessed by central independent review according to the RECIST 1.1.

Time frame: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression

Overall Survival (OS) Time

OS was defined as time from randomisation to death.

Time frame: From randomisation to cut-off date (17MAR2017).

Tumour Shrinkage

Tumour shrinkage was calculated as the minimum Sum of Diameters (SoD) of target lesions from all post-baseline tumour assessments, as read by the central independent review. The mean of these minimum values were presented after adjusting for baseline SoD, EGFR mutation group and race.

Time frame: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression

Data from ClinicalTrials.gov

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Highlands Oncology Group

Fayetteville, Arkansas, United States

Clinical Trials and Research Associates Inc

Montebello, California, United States

Innovative Medical Research of South Florida

Miami, Florida, United States

Crescent City Research Consortiom

Marrero, Louisiana, United States

Interlakes Foundation, Incorporated

Rochester, New York, United States

Lehigh Valley Hospital / Lehigh Valley Health Network

Allentown, Pennsylvania, United States

South Texas Institute of Cancer, Northwest Cancer Center

Corpus Christi, Texas, United States

Instituto de Medicina Nuclear de Bahía Blanca

Bahía Blanca, Argentina

Hospital Alemán

Capital Federal, Argentina

Imcaba S.R.L.

Capital Federal, Argentina

...and 123 more locations

Change From Baseline in Body Weight

Because the PFS was longer for patients in the Afatinib arm than for patients in the chemotherapy arm, the period of data collection for ECOG status and body weight continued for a longer time in the Afatinib arm.

Time frame: Baseline and throughout the trial until progression (every 3 weeks), up to 28 months.

Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)

ECOG PS measured on 6 point scale to assess participant's performance status. 0=Fully active, able to carry on all pre-disease activities without restriction. 1. Restricted in physically strenuous activity, but ambulatory and able to carry out light or sedentary work. 2. Ambulatory (\>50 percent of waking hours), capable of all self-care, unable to carry out any work activities. 3. Capable of only limited self-care, confined to bed or chair more than 50 percent of waking hours. 4. Completely disabled, cannot carry on any self-care, totally confined to bed or chair. 5. Dead.

Time frame: Throughout the trial until progression (every 3 weeks), up to 28 months.

Health Related Quality of Life (HRQOL): Time to Deterioration in Coughing

HRQOL was measured by European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire C30 (QLQ-C30) and its lung cancer specific module LC13 (QLQ-LC13). Analysis for cough is based on QLQ-LC13 question 1. Time to deterioration was defined as the time from randomisation to a score increased (worsened) by at least 10 points from baseline (0-100 point scale). Patients were considered deteriorated at time of death. Median time results from unstratified Kaplan-Meier estimates.

Time frame: Throughout the trial until progression (every 3 weeks).

HRQOL: Time to Deterioration in Dyspnoea

HRQOL was measured by EORTC QLQ-C30 and its lung cancer specific module QLQ-LC13. Analysis for dyspnoea is based on composite of QLQ-LC13 questions 3-5. Time to deterioration was defined as the time from randomisation to a score increased (worsened) by at least 10 points from baseline (0-100 point scale). Patients were considered deteriorated at time of death. Median time results from unstratified Kaplan-Meier estimates.

Time frame: Throughout the trial until progression (every 3 weeks).

HRQOL: Time to Deterioration in Pain

HRQOL was measured by EORTC QLQ-C30 and its lung cancer specific module QLQ-LC13. Analysis for pain is based on composite of QLQ-C30 questions 9 and 19. Time to deterioration was defined as the time from randomisation to a score increased (worsened) by at least 10 points from baseline (0-100 point scale). Patients were considered deteriorated at time of death. Median time results from unstratified Kaplan-Meier estimates.

Time frame: Throughout the trial until progression (every 3 weeks).

Trough Plasma Concentrations of Afatinib at Day 22

Trough plasma concentrations of Afatinib at Day 22 (course 2, visit 1) after multiple daily dosing of 40 mg Afatinib and after dose escalation to 50 mg or dose reduction to 30 mg or 20 mg.

Time frame: Day 22.

Trough Plasma Concentrations of Afatinib at Day 29

Trough plasma concentrations of Afatinib at day 29 (course 2, visit 2) after multiple daily dosing of 40 mg Afatinib and after dose escalation to 50 mg or dose reduction to 30 mg or 20 mg.

Time frame: Day 29.

Trough Plasma Concentrations of Afatinib at Day 43

Trough plasma concentrations of Afatinib at Day 43 (course 3, visit 1) after multiple daily dosing of 40 mg Afatinib and after dose escalation to 50 mg or dose reduction to 30 mg or 20 mg.

Time frame: Day 43.