BIBW 2992 (Afatinib) in Head & Neck Cancer

NCT00514943 | Completed Phase 2 Results

• 2 other identifiers: 1200.282008-007097-38
• Study Type: interventional
• Target: 124
• Locations: 4 countries
• Sites: 36

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.

Conditions

Head and Neck Neoplasms; Carcinoma, Squamous Cell

Outcome Measures

Primary Outcomes (1)

• Tumor Shrinkage Before Crossover (Stage 1) of the Trial as Per Investigator Assessment

  Tumor shrinkage before crossover was defined as the change from baseline in the smallest post-randomisation sum of the longest diameters of target lesions (SLD), calculated as the smallest SLD after randomisation but before crossover minus SLD at baseline. Baseline was the SLD measured before randomisation. A negative value means the smallest post-randomisation SLD was smaller than baseline (decreased since baseline); a positive value means tumor size increased since baseline. Mean calculated is actually the Adjusted mean. Adjusted mean is obtained from fitting an ANCOVA model including treatment, stratification factor prior chemotherapy for recurrent/metastatic disease and the baseline sum of longest distance of target lesions as covariates.

  From randomization until start of Stage 2 treatment, or within 28 days after the termination of Stage 1.

Secondary Outcomes (21)

• Tumor Shrinkage After Crossover (Stage 2) as Per Investigator Assessments

  From baseline assessed prior to first dose of Stage 2 study medication to 28 days after termination of Stage 2 treatment.

• 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).

  Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatment

• Best RECIST Assessment as Per ICR for Stage 1 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment).

  Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatment

• 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)

  Response determined during Stage 2 or within 28 days after termination of Stage 2 treatment

• Best RECIST Assessment as Per ICR for Stage2 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment)

  Response determined during Stage 2 or within 28 days after termination of Stage 2 treatment

Study Arms (2)

BIBW 2992

EXPERIMENTAL

once daily taken orally

Drug: BIBW 2992

Cetuximab

ACTIVE COMPARATOR

once every week by intravenous injection

Drug: Cetuximab

Interventions

BIBW 2992 DRUG

experimental drug taken once daily orally

BIBW 2992

Cetuximab DRUG

active comparator administered weekly intravenously

Cetuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Progressive disease within 3 months after completion of curative intent treatment for localized/locoregionally advanced disease.
• 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).
• More than 2 chemotherapeutic regimens given for recurrent/metastatic disease.
• 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
• eliminated per Amendment #1
• 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.
• Patients with history of decompensated heart failure.
• Cardiac left ventricular function with resting ejection fraction \<50% or less than the institutional lower limit of normal by MUGA or echocardiogram.
• Active infectious disease.
• Gastrointestinal disorders that may interfere with the absorption of the study drug or chronic diarrhea.
• Serious illness, concomitant non-oncological disease or mental problems considered by the investigator to be incompatible with the protocol.
• Use of alcohol or drugs incompatible with patient participation in the study in the investigator's opinion.
• Patients unable to comply with the protocol.
• 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.
• Absolute neutrophile count (ANC) less than 1000/mm3.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (36)

1200.28.0010 Boehringer Ingelheim Investigational Site

Stanford, California, United States

Location

1200.28.0001 Boehringer Ingelheim Investigational Site

Chicago, Illinois, United States

Location

1200.28.0005 Boehringer Ingelheim Investigational Site

Chicago, Illinois, United States

Location

1200.28.0011 Boehringer Ingelheim Investigational Site

Harvey, Illinois, United States

Location

1200.28.0022 Boehringer Ingelheim Investigational Site

Indianapolis, Indiana, United States

Location

1200.28.0024 Boehringer Ingelheim Investigational Site

Baltimore, Maryland, United States

Location

1200.28.0012 Boehringer Ingelheim Investigational Site

Ann Arbor, Michigan, United States

Location

1200.28.0021 Boehringer Ingelheim Investigational Site

Saint Joseph, Michigan, United States

Location

1200.28.0016 Boehringer Ingelheim Investigational Site

Rochester, Minnesota, United States

Location

1200.28.0002 Boehringer Ingelheim Investigational Site

Jackson, Mississippi, United States

Location

1200.28.0006 Boehringer Ingelheim Investigational Site

Omaha, Nebraska, United States

Location

1200.28.0008 Boehringer Ingelheim Investigational Site

New Hyde Park, New York, United States

Location

1200.28.0017 Boehringer Ingelheim Investigational Site

Chapel Hill, North Carolina, United States

Location

1200.28.0004 Boehringer Ingelheim Investigational Site

Winston-Salem, North Carolina, United States

Location

1200.28.0013 Boehringer Ingelheim Investigational Site

Charleston, South Carolina, United States

Location

1200.28.0007 Boehringer Ingelheim Investigational Site

Houston, Texas, United States

Location

1200.28.0009 Boehringer Ingelheim Investigational Site

Madison, Wisconsin, United States

Location

1200.28.0020 Boehringer Ingelheim Investigational Site

Milwaukee, Wisconsin, United States

Location

1200.28.0030 Boehringer Ingelheim Investigational Site

Brussels, Belgium

Location

1200.28.0031 Boehringer Ingelheim Investigational Site

Ghent, Belgium

Location

1200.28.0032 Boehringer Ingelheim Investigational Site

Leuven, Belgium

Location

1200.28.0062A Boehringer Ingelheim Investigational Site

Alès, France

Location

1200.28.0062B Boehringer Ingelheim Investigational Site

Alès, France

Location

1200.28.0059A Boehringer Ingelheim Investigational Site

Avignon, France

Location

1200.28.0052A Boehringer Ingelheim Investigational Site

Lille, France

Location

1200.28.0051A Boehringer Ingelheim Investigational Site

Lyon, France

Location

1200.28.0050A Boehringer Ingelheim Investigational Site

Montpellier, France

Location

1200.28.0058A Boehringer Ingelheim Investigational Site

Nîmes, France

Location

1200.28.0061A Boehringer Ingelheim Investigational Site

Poitiers, France

Location

1200.28.0055G Boehringer Ingelheim Investigational Site

Rouen, France

Location

1200.28.0040 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1200.28.0044 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1200.28.0043 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

1200.28.0042 Boehringer Ingelheim Investigational Site

Málaga, Spain

Location

1200.28.0045 Boehringer Ingelheim Investigational Site

Santander, Spain

Location

1200.28.0041 Boehringer Ingelheim Investigational Site

Valencia, Spain

Location

Related Publications (1)

• 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.

  PMID: 25057165 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms; Carcinoma, Squamous Cell

Interventions

Afatinib; Cetuximab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2007
• First Posted: August 10, 2007
• Study Start: August 1, 2007
• Primary Completion: March 1, 2010
• Study Completion: July 1, 2013
• Last Updated: July 26, 2016
• Results First Posted: December 25, 2013

Record last verified: 2016-06

Locations

US (18); BE (3); FR (9); ES (6)