Trial of BIBW 2992 (Afatinib) + Cetuximab in Non-Small Cell Lung Cancer

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

171 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-03-31

Study Completion Date

2014-08-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The primary objective of this trial is to determine the maximum tolerated dose (MTD) and recommended Phase II doses for the combination of BIBW 2992 and cetuximab in patients with non-small cell lung cancer and acquired resistance to erlotinib or gefitinib.

Overall safety, pharmacokinetics and anti-tumor activity for the combination of BIBW 2992 and cetuximab in patients with non-small cell lung cancer and acquired resistance to erlotinib, gefitinib or BIBW 2992 will be evaluated as secondary objectives.

Initially a standard, 3+3 dose escalation will be performed to determine the MTD of BIBW 2992 when administered together with cetuximab in patients with advanced non small cell lung cancer and acquired resistance to erlotinib or gefitinib.

Subsequently, the preliminary efficacy and safety of the identified MTD of cetuximab administered with BIBW 2992 will be explored in a combo arm via a further expansion of MTD cohort up to a total of 140 EGFR mutation positive NSCLC with acquired resistance to erlotinib/gefitinib.

Furthermore, the safety and preliminary anti-tumor activity of the combination therapy in EGFR mutant NSCLC patients who developed acquired resistance (AR) to BIBW 2992, will be assessed in a sequential arm. The sequential arm will use a two-stage design with an early stopping rule after 12 patients with acquired resistance to BIBW 2992 have received up to 5 courses of BIBW 2992 plus cetuximab. If no responses are seen in 12 patients during 5 courses of combination therapy, accrual in the sequential arm will stop. If 1 or more responses are observed, the sequential arm will expand up to about 40 patients.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Single-arm Trial of BIBW 2992 (Afatinib) in Demographically and Genotypically Selected NSCLC Patients

NCT00730925

Carcinoma, Non-Small-Cell Lung

COMPLETED PHASE2

BIBW 2992 (Afatinib) vs Gemcitabine-cisplatin in 1st Line Non-small Cell Lung Cancer (NSCLC)

NCT01121393

Carcinoma, Non-Small-Cell Lung Adenocarcinoma

COMPLETED PHASE3

An Open Label Study of BIBW 2992/Afatinib in Advanced Non-Small Cell Lung Cancer Patients Pre-treated With Erlotinib or Gefitinib

NCT01932229

NSCLC

UNKNOWN PHASE2

LUX-Lung 4: BIBW 2992 (Afatinib) Phase I Trial in Advanced Non Small Cell Lung Cancer Patients & Phase II Trial in Non Small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib

NCT00711594

Carcinoma, Non-Small-Cell Lung

COMPLETED PHASE2

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

NCT00949650

Carcinoma, Non-Small-Cell Lung Adenocarcinoma

COMPLETED PHASE3

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Carcinoma, Non-Small-Cell Lung

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

combination arm

patients to receive medium BIBW 2992 once daily plus biweekly cetuximab infusion at low, median and high dose level

Group Type EXPERIMENTAL

Cetuximab

Intervention Type DRUG

BIBW 2992 medium dose plus high dose level of cetuximab

BIBW 2992

Intervention Type DRUG

BIBW 2992 medium dose plus high dose level of cetuximab

sequential arm

patients to receive BIBW 2992 once daily, upon progression add biweekly cetuximab

Group Type EXPERIMENTAL

Cetuximab

Intervention Type DRUG

BIBW 2992 medium dose monotherapy, upon progression, cetuximab high dose is added

BIBW 2992

Intervention Type DRUG

BIBW 2992 medium dose monotherapy, upon progression, cetuximab high dose is added

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Cetuximab

BIBW 2992 medium dose plus high dose level of cetuximab

Intervention Type DRUG

Cetuximab

BIBW 2992 medium dose monotherapy, upon progression, cetuximab high dose is added

Intervention Type DRUG

BIBW 2992

BIBW 2992 medium dose plus high dose level of cetuximab

Intervention Type DRUG

BIBW 2992

BIBW 2992 medium dose monotherapy, upon progression, cetuximab high dose is added

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Pathologically or cytologically confirmed Stage IIIB/IV non-small cell lung cancer or recurrent disease following locoregional treatment
2. Either or both of the following:

1\) A tumor which harbors an Epidermal Growth Factor Receptor (EGFR) -mutation known to be associated with drug sensitivity (i.e., G719X, exon 19 deletion, L858R, L861Q) from previous tumor biopsy or surgery. A tumor which harbors exon 20 insertion or de novo T790M mutation is eligible for the treatment in the sequential arm 2) Objective clinical benefit from treatment with an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) as defined by either

1. Documented partial or complete response (Response Evaluation Criteria in Solid Tumors, RECIST), or
2. Stable disease \>=6 months as defined by RECIST in absence of radiographic progression after initiation of gefitinib or erlotinib; or stable disease/PR/CR \>=12 weeks as defined by RECIST after initiation of BIBW 2992 3. Systemic progression of disease (RECIST v1.1) while on continuous treatment with erlotinib or gefitinib or BIBW 2992 within the last 30 days. Patients whose disease progresses only in the central nervous system (CNS) are not eligible 4. No intervening systemic therapy between cessation of gefitinib or erlotinib or BIBW 2992 and initiation of the treatment in the study 5. Adequate tumor-derived material such as fresh or archived tumor tissue or pleural fluid from malignant pleural effusion after disease progression on erlotinib/gefitinib/BIBW 2992 prior to the study entry must be made available for EGFR mutation analyses 6. Patients aged 18 years or older 7. Life expectancy of at least three (3) months 8. Eastern Cooperative Oncology Group (ECOG) performance score 0-2 9. Written informed consent that is consistent with ICH-GCP guidelines

Exclusion Criteria

1. Prior treatment with EGFR targeting antibodies; prior severe infusion reaction to a monoclonal antibody
2. Adverse events due to major surgery (at least 28 days after) or minor surgery not recovered to CTC grade 1 or less. Surgical wounds must be healing without clinical evidence of infection prior to study treatment to be eligible.
3. Radiotherapy less than two weeks prior to the start of the study treatment
4. Systemic chemotherapy, hormonal therapy, immunotherapy, or experimental or approved proteins/antibodies (except erlotinib/gefitinib/BIBW 2992) \<=30 days before study treatment
5. Less than three days from prior treatment with gefitinib or erlotinib. Patients with adverse events related to gefitinib or erlotinib must recover to CTC AE grade 1 or less to be eligible. No need to stop BIBW 2992 before start of the study treatment for patient who progressed on BIBW 2992 from a separate clinical trial/treatment setting
6. Brain metastases, which are symptomatic. Patients with treated, asymptomatic brain metastases are eligible if there has been no change in brain disease status for at least four (4) weeks, no history of cerebral oedema or bleeding in the past four (4) weeks. Anticonvulsant therapy will be allowed if patient is stable on anticonvulsant treatment.
7. Other malignancies diagnosed within the past five (5) years (other than non melanomatous skin cancer, ductal carcinoma in situ and in situ cervical cancer)
8. Known pre-existing interstitial lung disease
9. Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom e.g., Crohns disease, malabsorption, or Common Toxicity Criteria for Adverse Events (CTCAE) grade \>2 diarrhea of any etiology
10. Women of childbearing potential (WOCBP), or men who are able to father a child, unwilling to use a medically acceptable method of contraception during the trial; pregnancy or breast-feeding

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No