Carcinoma, Non-Small-Cell LungPhase 1NCT01090011
Trial of BIBW 2992 (Afatinib) + Cetuximab in Non-Small Cell Lung Cancer
A Phase 1 study testing Cetuximab and BIBW 2992 in people with Carcinoma, Non-Small-Cell Lung, run by Boehringer Ingelheim at 6 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung
- What is being tested?
- Cetuximab and BIBW 2992
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 171 participants
- Where
- 6 sitesin 2 countries
- Study dates
- Mar 2010to Aug 2014
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically or cytologically confirmed Stage IIIB/IV non-small cell lung cancer or recurrent disease following locoregional treatment
- 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
- Documented partial or complete response (Response Evaluation Criteria in Solid Tumors, RECIST), or
- 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
Who cannot join
- Prior treatment with EGFR targeting antibodies; prior severe infusion reaction to a monoclonal antibody
- 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.
- Radiotherapy less than two weeks prior to the start of the study treatment
- Systemic chemotherapy, hormonal therapy, immunotherapy, or experimental or approved proteins/antibodies (except erlotinib/gefitinib/BIBW 2992) <=30 days before study treatment
- 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
- 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.
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- Other malignancies diagnosed within the past five (5) years (other than non melanomatous skin cancer, ductal carcinoma in situ and in situ cervical cancer)
- Known pre-existing interstitial lung disease
- 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
- 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
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
United States4 sites
1200.71.1004 Boehringer Ingelheim Investigational Site
Aurora, Colorado
1200.71.1002 Boehringer Ingelheim Investigational Site
Nashville, Tennessee
1200.71.1003 Boehringer Ingelheim Investigational Site
New Haven, Connecticut
1200.71.1001 Boehringer Ingelheim Investigational Site
New York, New York
Netherlands2 sites
1200.71.2002 Boehringer Ingelheim Investigational Site
Amsterdam
1200.71.2001 Boehringer Ingelheim Investigational Site
Groningen
About this study
Official title: A Phase Ib Open-label Clinical Trial of Continuous Once Daily Oral Treatment Using BIBW 2992 Plus Cetuximab (Erbitux®) in Patients With Non-small Cell Lung Cancer With Progression Following Prior Erlotinib (Tarceva®) or Gefitinib (Iressa®)
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.
Read more
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.
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Being tested
- Cetuximab, BIBW 2992
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CetuximabDrug
BIBW 2992 medium dose plus high dose level of cetuximab
CetuximabDrug
BIBW 2992 medium dose monotherapy, upon progression, cetuximab high dose is added
BIBW 2992Drug
BIBW 2992 medium dose plus high dose level of cetuximab
BIBW 2992Drug
BIBW 2992 medium dose monotherapy, upon progression, cetuximab high dose is added
| Study group | Role | What they receive |
|---|---|---|
| combination arm | Experimental | patients to receive medium BIBW 2992 once daily plus biweekly cetuximab infusion at low, median and high dose level Receives: Drug: Cetuximab; Drug: BIBW 2992 |
| sequential arm | Experimental | patients to receive BIBW 2992 once daily, upon progression add biweekly cetuximab Receives: Drug: Cetuximab; Drug: BIBW 2992 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Primary Endpoint is the Occurrence of Dose Limiting Toxicity (DLT).
A DLT was defined as an AE or laboratory abnormality that a) related to the study regimen; b) or met any of the following criteria:
- CTCAE Grade 2 or higher decrease in cardiac left ventricular function
- CTCAE Grade 2 diarrhea lasting for 7 or more days, despite appropriate use of standard anti-diarrheal therapy
- CTCAE Grade ≥3 diarrhea despite appropriate use of standard anti-diarrheal therapy for at least 2 days
- CTCAE Grade ≥3 nausea and/or vomiting despite appropriate use of standard anti-emetics for at least 3 days
- CTCAE Grade ≥3 rash despite standard medical management
- CTCAE Grade ≥3 fatigue lasting for more than 7 days
- CTCAE Grade 4 hypomagnesaemia or Grade 3 hypomagnesaemia with clinical significant sequelae
- All other toxicities of CTCAE Grade ≥3 (except alopecia, and allergic reaction) leading to an interruption of afatinib and/or cetuximab for more than 14 days until recovery to baseline or Grade 1, whichever was higher.
Measured: from day 1 treatment until progression or undue toxicity, up to 28 days
Secondary outcomes (19)
Highest CTCAE Grade
Safety of afatinib when administered together with cetuximab as indicated by intensity and incidence of adverse events, graded according to the U.S. National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Version (v) 3.0
Measured: From first drug administration to 28 days after discontinuation of drug intake up to 915 days
Frequency of Patients [N(%)] With Possible Clinically Significant Abnormalities for Selected Laboratory Parameters
Measured: From first drug administration to 28 days after discontinuation of drug intake up to 915 days
Frequency (%) of Patients With Adverse Events Leading to Dose Reduction
Measured: From first drug administration to 28 days after discontinuation of drug intake up to 915 days
Frequency (%) of Patients With Adverse Events Leading to Treatment Discontinuation
Frequency (%) of patients with adverse events leading to treatment discontinuation
Measured: From first drug administration to 28 days after discontinuation of drug intake up to 915 days
Frequency (%) of Patients With Adverse Events Leading to Death
Measured: From first drug administration to 28 days after discontinuation of drug intake up to 915 days
Frequency (%) of Patients With Related Serious Adverse Events
Frequency (%) of patients with drug-related serious adverse events
Measured: From first drug administration to 28 days after discontinuation of drug intake up to 915 days
Area Under the Concentration-time Curve (AUC) on Day 15 of Plasma Afatinib for the Combination Arm
Area Under the Concentration-time Curve (AUC) of Afatinib in plasma at steady state over a uniform dosing interval tau (15 days) (AUCtau,ss) after oral administration of Afatinib and cetuximab combination therapy
Measured: Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55
Concentration of Afatinib in Plasma for the Combination Arm
Minimum measured concentration of Afatinib in plasma at steady state over 15 day dosing interval (Cmin,ss). Maximum measured concentration of Afatinib in plasma at steady state over 15 day dosing interval (Cmax,ss).
Measured: Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55
Peak-trough Fluctuation (PTF)
Peak-trough fluctuation (PTF) of plasma afatinib for the combination arm. PTF = 100*(Cmax-Cmin)/Caverage where Caverage = AUC/time, where time equals 24 hours.
Measured: Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55
t1/2,ss
Terminal half-life of Afatinib in plasma at steady state (t1/2,ss)
Measured: Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55
MRTpo,ss
mean residence time of Afatinib in the body at steady state after oral administration (MRTpo,ss) for 15 days
Measured: Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55
CL/F,ss,15
Apparent clearance of afatinib in plasma at steady state after extravascular multiple dose administration (CL/F,ss)
Measured: Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55
Vz/F,ss
Apparent volume of distribution during the terminal phase λz at steady state following extravascular administration (Vz/F,ss) for 15 days
Measured: Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55
Predose Plasma Concentrations of Afatinib for the Combination Arm
Predose plasma concentrations (Cpre,ss) of Afatinib at Course 1, Visit 2, 3, 4 and 5, at Course 2, Visit 1 and 2 and at Course 3, Visit 1.
Measured: Up to 57 days
Disease Control (CR, PR and Stable Disease (SD) Determined by RECIST v1.1)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), At least a 20% increase in the sum of the longest diameter of target lesions or the appearance of new lesion(s); Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Disease control = CR + PR + SD.
Measured: up to 116 weeks
Objective Tumor Response (Complete Response [CR] and Partial Response [PR]) Determined by RECIST v1.1)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), At least a 20% increase in the sum of the longest diameter of target lesions or the appearance of new lesion(s); Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Objective tumor response = CR + PR.
Measured: up to 116 weeks
Duration of Objective Response (According to RECIST v1.1)
Duration of objective response was measured from the time measurements criteria were met for CR/PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded since treatment started).
Measured: up to 116 weeks
Duration of Disease Control (According to RECIST v1.1)
Duration of disease control was defined as the time from the start of treatment to the time of progression or death (whichever occurred first), among patients with evidence SD, PR or CR.
Measured: up to 116 weeks
Progression-Free Survival (PFS) Time
Progression-Free Survival was defined as the duration of time from start of treatment until the day of objective tumour progression confirmed by tumour imaging (PD according to RECIST 1.1) or death.
Measured: up to 116 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2010 (estimated)
- Study startMar 2010
- Primary completionJan 2013
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 171 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01090011
- Sponsor's protocol ID
- 1200.71
- Other IDs
- 2009-015911-42, 2009
- Status last verified
- Aug 2015
- First submitted
- 10 Mar 2010
- Last updated
- 2 Oct 2015
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Horn L, Gettinger S, Camidge DR, Smit EF, Janjigian YY, Miller VA, Pao W, Freiwald M, Fan J, Wang B, Chand VK, Groen HJM. Continued use of afatinib with the addition of cetuximab after progression on afatinib in patients with EGFR mutation-positive non-small-cell lung cancer and acquired resistance to gefitinib or erlotinib. Lung Cancer. 2017 Nov;113:51-58. doi: 10.1016/j.lungcan.2017.08.014. Epub 2017 Aug 31.
PubMed 29110849Janjigian YY, Smit EF, Groen HJ, Horn L, Gettinger S, Camidge DR, Riely GJ, Wang B, Fu Y, Chand VK, Miller VA, Pao W. Dual inhibition of EGFR with afatinib and cetuximab in kinase inhibitor-resistant EGFR-mutant lung cancer with and without T790M mutations. Cancer Discov. 2014 Sep;4(9):1036-45. doi: 10.1158/2159-8290.CD-14-0326. Epub 2014 Jul 29.
PubMed 25074459
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Open-label Clinical Trial of Continuous Once Daily Oral Treatment Using BIBW 2992 Plus Cetuximab (Erbitux®) in Patients With Non-small Cell Lung Cancer With Progression Following Prior Erlotinib (Tarceva®) or Gefitinib (Iressa®)
- ClinicalTrials.gov ID
- NCT01090011
- Acronym / sponsor ID
- 1200.71
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 171 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- Mar 2010
- Primary completion
- Jan 2013 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 19 Mar 2010 (estimated)
- Results
- Posted 21 Jul 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| combination arm | Experimental | Drug: Cetuximab, Drug: BIBW 2992patients to receive medium BIBW 2992 once daily plus biweekly cetuximab infusion at low, median and high dose level |
| sequential arm | Experimental | Drug: Cetuximab, Drug: BIBW 2992patients to receive BIBW 2992 once daily, upon progression add biweekly cetuximab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Pathologically or cytologically confirmed Stage IIIB/IV non-small cell lung cancer or recurrent disease following locoregional treatment
- 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
- Documented partial or complete response (Response Evaluation Criteria in Solid Tumors, RECIST), or
- 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
Key exclusion criteria (10 listed)
- Prior treatment with EGFR targeting antibodies; prior severe infusion reaction to a monoclonal antibody
- 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.
- Radiotherapy less than two weeks prior to the start of the study treatment
- Systemic chemotherapy, hormonal therapy, immunotherapy, or experimental or approved proteins/antibodies (except erlotinib/gefitinib/BIBW 2992) <=30 days before study treatment
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CetuximabBIBW 2992 medium dose plus high dose level of cetuximab | Drug | combination arm |
| CetuximabBIBW 2992 medium dose monotherapy, upon progression, cetuximab high dose is added | Drug | sequential arm |
| BIBW 2992BIBW 2992 medium dose plus high dose level of cetuximab | Drug | combination arm |
| BIBW 2992BIBW 2992 medium dose monotherapy, upon progression, cetuximab high dose is added | Drug | sequential arm |
Primary outcome
The Primary Endpoint is the Occurrence of Dose Limiting Toxicity (DLT).
Time frame: from day 1 treatment until progression or undue toxicity, up to 28 days
A DLT was defined as an AE or laboratory abnormality that a) related to the study regimen; b) or met any of the following criteria: * CTCAE Grade 2 or higher decrease in cardiac left ventricular function * CTCAE Grade 2 diarrhea lasting for 7 or more days, despite appropriate use of standard anti-diarrheal therapy * CTCAE Grade ≥3 diarrhea despite appropriate use of standard anti-diarrheal therapy for at least 2 days * CTCAE Grade ≥3 nausea and/or vomiting despite appropriate use of standard anti-emetics for at least 3 days * CTCAE Grade ≥3 rash despite standard medical management * CTCAE Grade ≥3 fatigue lasting for more than 7 days * CTCAE Grade 4 hypomagnesaemia or Grade 3 hypomagnesaemia with clinical significant sequelae * All other toxicities of CTCAE Grade ≥3 (except alopecia, and allergic reaction) leading to an interruption of afatinib and/or cetuximab for more than 14 days until recovery to baseline or Grade 1, whichever was higher.
19 secondary outcomes
Highest CTCAE Grade
Time frame: From first drug administration to 28 days after discontinuation of drug intake up to 915 days
Frequency of Patients [N(%)] With Possible Clinically Significant Abnormalities for Selected Laboratory Parameters
Time frame: From first drug administration to 28 days after discontinuation of drug intake up to 915 days
Frequency (%) of Patients With Adverse Events Leading to Dose Reduction
Time frame: From first drug administration to 28 days after discontinuation of drug intake up to 915 days
Frequency (%) of Patients With Adverse Events Leading to Treatment Discontinuation
Time frame: From first drug administration to 28 days after discontinuation of drug intake up to 915 days
Frequency (%) of Patients With Adverse Events Leading to Death
Time frame: From first drug administration to 28 days after discontinuation of drug intake up to 915 days
Frequency (%) of Patients With Related Serious Adverse Events
Time frame: From first drug administration to 28 days after discontinuation of drug intake up to 915 days
Area Under the Concentration-time Curve (AUC) on Day 15 of Plasma Afatinib for the Combination Arm
Time frame: Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55
Concentration of Afatinib in Plasma for the Combination Arm
Time frame: Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55
Peak-trough Fluctuation (PTF)
Time frame: Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55
t1/2,ss
Time frame: Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55
MRTpo,ss
Time frame: Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55
CL/F,ss,15
Time frame: Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55
Vz/F,ss
Time frame: Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55
Predose Plasma Concentrations of Afatinib for the Combination Arm
Time frame: Up to 57 days
Disease Control (CR, PR and Stable Disease (SD) Determined by RECIST v1.1)
Time frame: up to 116 weeks
Objective Tumor Response (Complete Response [CR] and Partial Response [PR]) Determined by RECIST v1.1)
Time frame: up to 116 weeks
Duration of Objective Response (According to RECIST v1.1)
Time frame: up to 116 weeks
Duration of Disease Control (According to RECIST v1.1)
Time frame: up to 116 weeks
Progression-Free Survival (PFS) Time
Time frame: up to 116 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29110849Horn L, Gettinger S, Camidge DR, Smit EF, Janjigian YY, Miller VA, Pao W, Freiwald M, Fan J, Wang B, Chand VK, Groen HJM. Continued use of afatinib with the addition of cetuximab after progression on afatinib in patients with EGFR mutation-positive non-small-cell lung cancer and acquired resistance to gefitinib or erlotinib. Lung Cancer. 2017 Nov;113:51-58. doi: 10.1016/j.lungcan.2017.08.014. Epub 2017 Aug 31.
- Derived from this study: PubMed 25074459Janjigian YY, Smit EF, Groen HJ, Horn L, Gettinger S, Camidge DR, Riely GJ, Wang B, Fu Y, Chand VK, Miller VA, Pao W. Dual inhibition of EGFR with afatinib and cetuximab in kinase inhibitor-resistant EGFR-mutant lung cancer with and without T790M mutations. Cancer Discov. 2014 Sep;4(9):1036-45. doi: 10.1158/2159-8290.CD-14-0326. Epub 2014 Jul 29.
- Related InfoLink provided by the sponsor.
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Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boehringer Ingelheim study chair
Boehringer Ingelheim
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cetuximab and BIBW 2992 in people with Carcinoma, Non-Small-Cell Lung, run by Boehringer Ingelheim at 6 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Primary Endpoint is the Occurrence of Dose Limiting Toxicity (DLT). (time frame: from day 1 treatment until progression or undue toxicity, up to 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01090011, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2015; AzTrials last refreshed its copy on 8 Nov 2026.