Clinical trial NCT00514943: BIBW 2992 (Afatinib) in Head & Neck Cancer
Official title: A Randomized, Open-label Phase II Study of BIBW 2992 Versus Cetuximab (Erbitux) in Patients With Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma (HNSCC) After Failure of Platinum-containing Therapy With a Cross-over Period for Progressing Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Head and Neck Neoplasms
Carcinoma, Squamous Cell
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2007-08-10
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to explore the efficacy of BIBW 2992 compared with cetuximab (Erbitux) in patients with metastatic or recurrent head and neck cancer after failure of platinum-containing therapy. In addition, the trial aims to clarify the influence of EGFR genotype on tumor response to the treatment regimens.


Eligibility criteria: Inclusion criteria:

1. Metastatic (stage IVc) or recurrent HNSCC 2. Histologically or cytologically confirmed diagnosis of squamous cell of the head and neck. Patients with well-differentiated (keratinizing) nasopharyngeal carcinomas and patients with squamous cell carcinomas metastatic to the neck from an unknown head and neck primary are eligible. 3. Patients must have documented progressive disease (PD) following receipt of prior platinum-based therapy (either as neoadjuvant, adjuvant, concomitant with radiotherapy, or for recurrent/ metastatic disease). 4. Patients must have measurable disease as defined by RECIST criteria. 5. Patients must have recovered from any therapy-related toxicities from previous chemo-, immuno-, or radiotherapies to CTC smaller or equal to Grade 1. 6. Patients must have recovered from previous surgery. 7. Life expectancy of at least three (3) months. 8. Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score 0 or 1.

9. Patients must be eighteen (18) years of age or older. 10. Willingness and ability to give written informed consent consistent with ICH-GCP guidelines.

Exclusion criteria:

1. Progressive disease within 3 months after completion of curative intent treatment for localized/locoregionally advanced disease.
2. Prior use of an EGFR or erbB2 inhibitor in the recurrent/metastatic disease setting (treatment with cetuximab (Erbitux®) or other EGFR inhibitor during radiotherapy or chemoradiotherapy is permissible).
3. More than 2 chemotherapeutic regimens given for recurrent/metastatic disease.
4. Treatment with other investigational drugs, other anti-cancer-therapy (e.g., chemotherapy, immunotherapy, radiotherapy), concomitantly with therapy on this study and/or during the last four weeks, prior to the first treatment with the trial drug
5. eliminated per Amendment #1
6. Patients with history of other malignancy (except for appropriately treated superficial basal cell skin cancer and surgically cured cervical cancer in situ) unless free of disease for at least 3 years.
7. Patients with history of decompensated heart failure.
8. Cardiac left ventricular function with resting ejection fraction \<50% or less than the institutional lower limit of normal by MUGA or echocardiogram.
9. Active infectious disease.
10. Gastrointestinal disorders that may interfere with the absorption of the study drug or chronic diarrhea.
11. Serious illness, concomitant non-oncological disease or mental problems considered by the investigator to be incompatible with the protocol.
12. Use of alcohol or drugs incompatible with patient participation in the study in the investigator's opinion.
13. Patients unable to comply with the protocol.
14. Patients with active/symptomatic brain metastases. Patients with a history of treated brain metastases must have stable or normal cerebral MRI scan at screening and be at least three months post-radiation or surgery.
15. Absolute neutrophile count (ANC) less than 1000/mm3.
16. Platelet count less than 75,000/mm3.
17. Bilirubin greater than 1.5 mg/dl/ Higher bilirubin values are acceptable for patients with known Gilbert's disease, approval by the PI and sponsor necessary.
18. Asparate amino transferase (AST) or alanine amino transferase (ALT) greater than 3 times the upper limit of normal.
19. Serum creatinine greater than 1.5 X upper limit of normal for the institution.
20. Patients who are sexually active and unwilling to use a medically acceptable method of contraception.
21. Pregnancy or breast-feeding.
22. Patients with known pre-existing interstitial lung disease.

Primary outcomes:
measure: Tumor Shrinkage Before Crossover (Stage 1) of the Trial as Per Investigator Assessment
timeFrame: From randomization until start of Stage 2 treatment, or within 28 days after the termination of Stage 1.
Secondary outcomes:
measure: Tumor Shrinkage After Crossover (Stage 2) as Per Investigator Assessments
timeFrame: From baseline assessed prior to first dose of Stage 2 study medication to 28 days after termination of Stage 2 treatment.
measure: Best RECIST Assessment as Per Investigator Assessment for Stage 1 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment).
timeFrame: Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatment
measure: Best RECIST Assessment as Per ICR for Stage 1 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment).
timeFrame: Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatment
measure: Best RECIST Assessment as Per Investigator Assessment for Stage 2 (as as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment)
timeFrame: Response determined during Stage 2 or within 28 days after termination of Stage 2 treatment
measure: Best RECIST Assessment as Per ICR for Stage2 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment)
timeFrame: Response determined during Stage 2 or within 28 days after termination of Stage 2 treatment
measure: Best RECIST Assessment as Onset of Confirmed Objective Response as Per Investigator Assessment for Stage 1
timeFrame: Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatment
measure: Best RECIST Assessment as Onset of Confirmed Objective Response as as Per ICR for Stage 1
timeFrame: Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatment
measure: Best RECIST Assessment as Onset of Confirmed Objective Response as Per Investigator Assessment for Stage 2
timeFrame: Response determined during Stage 2 or within 28 days after termination of Stage 2 treatment
measure: Best RECIST Assessment as Confirmed Duration of Objective Response and Disease Control as Per Investigator Assessment for Stage 1
timeFrame: Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatment
measure: Best RECIST Assessment as Confirmed Duration of Confirmed Objective Response and Disease Control as Per ICR for Stage 1
timeFrame: Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatment
measure: Best RECIST Assessment as Confirmed Duration of Objective Response and Disease Control as Per Investigator Assessment for Stage 2
timeFrame: Response determined during Stage 2 or within 28 days after termination of Stage 2 treatment
measure: Best RECIST Assessment as Confirmed Duration of Disease Control as Per ICR for Stage 2
timeFrame: Response determined during Stage 2 or within 28 days after termination of Stage 2 treatment
measure: Progression Free Survival (PFS) Before Crossover Based on Investigator Assessment
timeFrame: From randomisation to disease progression in Stage 1 or death whichever occurred first before crossover.
measure: Progression Free Survival (PFS) After Crossover Based on Investigator Assessment
timeFrame: From first administration of study medication after cross over to disease progression in Stage 2 or death whichever came first after crossover.
measure: Overall Survival (OS)
timeFrame: From randomisation to data cut-off date.
measure: Time to Deterioration in HRQoL - Stage 1
timeFrame: From randomisation to deterioration in HRQoL scores before crossover.
measure: Patients With AEs Resulting in Diarrhea, Skin Rash, Dose Reduction, Treatment Discontinuation and Decreased Cardiac Left Ventricular Function
timeFrame: First administration of trial medication until 28 days after last drug administration
measure: Incidence and Intensity of Adverse Events With Grading According CTCAE
timeFrame: First administration of trial medication until 28 days after last drug administration
measure: Pre-dose Concentration of Afatinib in Plasma for Dose 40mg and 50mg at Steady State on Day 15 (Cpre,ss,15)
timeFrame: Day 15
measure: Pre-dose Concentration of Afatinib in Plasma for Dose 40mg and 50mg at Steady State on Day 29 (Cpre,ss,29)
timeFrame: Day 29
measure: Pre-dose Concentration of Afatinib in Plasma for Dose 40mg and 50mg at Steady State on Day 57 (Cpre,ss, 57)
timeFrame: Day 57
Other outcomes:
Locations:
city: Stanford
country: United States
facility: 1200.28.0010 Boehringer Ingelheim Investigational Site
state: California
city: Chicago
country: United States
facility: 1200.28.0001 Boehringer Ingelheim Investigational Site
state: Illinois
city: Chicago
country: United States
facility: 1200.28.0005 Boehringer Ingelheim Investigational Site
state: Illinois
city: Harvey
country: United States
facility: 1200.28.0011 Boehringer Ingelheim Investigational Site
state: Illinois
city: Indianapolis
country: United States
facility: 1200.28.0022 Boehringer Ingelheim Investigational Site
state: Indiana
city: Baltimore
country: United States
facility: 1200.28.0024 Boehringer Ingelheim Investigational Site
state: Maryland
city: Ann Arbor
country: United States
facility: 1200.28.0012 Boehringer Ingelheim Investigational Site
state: Michigan
city: St. Joseph
country: United States
facility: 1200.28.0021 Boehringer Ingelheim Investigational Site
state: Michigan
city: Rochester
country: United States
facility: 1200.28.0016 Boehringer Ingelheim Investigational Site
state: Minnesota
city: Jackson
country: United States
facility: 1200.28.0002 Boehringer Ingelheim Investigational Site
state: Mississippi
city: Omaha
country: United States
facility: 1200.28.0006 Boehringer Ingelheim Investigational Site
state: Nebraska
city: New Hyde Park
country: United States
facility: 1200.28.0008 Boehringer Ingelheim Investigational Site
state: New York
city: Chapel Hill
country: United States
facility: 1200.28.0017 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: 1200.28.0004 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Charleston
country: United States
facility: 1200.28.0013 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Houston
country: United States
facility: 1200.28.0007 Boehringer Ingelheim Investigational Site
state: Texas
city: Madison
country: United States
facility: 1200.28.0009 Boehringer Ingelheim Investigational Site
state: Wisconsin
city: Milwaukee
country: United States
facility: 1200.28.0020 Boehringer Ingelheim Investigational Site
state: Wisconsin
city: Bruxelles
country: Belgium
facility: 1200.28.0030 Boehringer Ingelheim Investigational Site
city: Gent
country: Belgium
facility: 1200.28.0031 Boehringer Ingelheim Investigational Site
city: Leuven
country: Belgium
facility: 1200.28.0032 Boehringer Ingelheim Investigational Site
city: Ales
country: France
facility: 1200.28.0062A Boehringer Ingelheim Investigational Site
city: Ales
country: France
facility: 1200.28.0062B Boehringer Ingelheim Investigational Site
city: Avignon
country: France
facility: 1200.28.0059A Boehringer Ingelheim Investigational Site
city: Lille
country: France
facility: 1200.28.0052A Boehringer Ingelheim Investigational Site
city: Lyon
country: France
facility: 1200.28.0051A Boehringer Ingelheim Investigational Site
city: Montpellier cedex 5
country: France
facility: 1200.28.0050A Boehringer Ingelheim Investigational Site
city: Nimes cedex 9
country: France
facility: 1200.28.0058A Boehringer Ingelheim Investigational Site
city: Poitiers
country: France
facility: 1200.28.0061A Boehringer Ingelheim Investigational Site
city: Rouen
country: France
facility: 1200.28.0055G Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1200.28.0040 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1200.28.0044 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1200.28.0043 Boehringer Ingelheim Investigational Site
city: Malaga
country: Spain
facility: 1200.28.0042 Boehringer Ingelheim Investigational Site
city: Santander
country: Spain
facility: 1200.28.0045 Boehringer Ingelheim Investigational Site
city: Valencia
country: Spain
facility: 1200.28.0041 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Psyrri A, Rampias T, Vermorken JB. The current and future impact of human papillomavirus on treatment of squamous cell carcinoma of the head and neck. Ann Oncol. 2014 Nov;25(11):2101-2115. doi: 10.1093/annonc/mdu265. Epub 2014 Jul 23.