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LUX-Head&Neck 3: Afatinib (BIBW2992) Versus Methotrexate for the Treatment of Recurrent and/or Metastatic Head and Neck Squamous Cell Cancer After Platinum Based Chemotherapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2017 by Boehringer Ingelheim
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01856478
First received: May 15, 2013
Last updated: January 4, 2017
Last verified: January 2017
  Purpose
This randomized, open-label, phase III study will be performed in patients with recurrent and/or metastatic head and neck cancer which has progressed after platinum-based therapy. The objectives of this trial are to compare the efficacy and safety of afatinib versus methotrexate.

Condition Intervention Phase
Head and Neck Neoplasms
Drug: methotrexate
Drug: afatinib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomised, Open-label, Phase III Study to Evaluate the Efficacy and Safety of Oral Afatinib (BIBW 2992) Versus Intravenous Methotrexate in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma Who Have Progressed After Platinum-based Therapy

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • progression free survival (PFS), defined as the time from the date of randomization to the date of progression evaluated according to RECIST 1.1 or to the date of death, whichever occurs first [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival (OS), defined as the time from the date of randomization to the date of death (regardless of the cause of death) [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
  • Objective response defined as complete response (CR) or partial response (PR) determined by RECIST 1.1 according to the best response to study medication [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
  • Health related quality of life (HRQOL) will be assessed based on patient-reported questionaires [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 330
Study Start Date: May 2013
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: afatinib
oral intake, once daily
Drug: afatinib
oral intake, once daily
Active Comparator: methotrexate
intravenous bolus injection, once weekly
Drug: methotrexate
intravenous bolus injection, once weekly

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Histologically or cytologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx, which has recurred/metastasised and is not amenable for salvage surgery or radiotherapy.
  2. Documented progressive disease based on investigator assessment according to RECIST, following receipt of a cisplatin and/or carboplatin and/or Nedaplatin based regimen administered for recurrent and/or metastatic disease independent of whether patient progressed during or after platinum based therapy.
  3. Measurable disease according to RECIST (version 1.1).
  4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at Visit 2.
  5. Male and female patients age is 18 years or older
  6. Signed and dated written informed consent that is in compliance with ICH-GCP and local law.

Exclusion criteria:

  1. Progressive disease within three months after completion of curatively intended treatment for locoregionally advanced or for metastatic head and neck squamous cell cancer (HNSCC).
  2. Primary tumour site nasopharynx (of any histology), sinuses, and/or salivary glands.
  3. Any other than one previous platinum based systemic regimen given for recurrent and/or metastatic disease. Re-challenge with the first line regimen after a temporary break is considered a second line regimen only in case of progression within the break.
  4. Prior treatment with EGFR-targeted small molecules.
  5. Treatment with any investigational drug less than four weeks or anti-cancer therapy less than three weeks prior to randomization (except palliative radiotherapy to bones to alleviate pain).
  6. Unresolved chronic toxicity, other than hearing loss, tinnitus or dry mouth, CTCAE grade >2 from previous anti-cancer therapy or unresolved skin toxicities CTCAE grade >1 and/or diarrhoea CTCAE grade >1 caused by prior treatment with EGFR targeted antibodies.
  7. Previous tumour bleeding CTCAE grade =3.
  8. Requirement for treatment with any of the prohibited concomitant medications.
  9. Major surgical or planned procedure less than four weeks prior to randomization (isolated biopsies are not considered as major surgical procedures).
  10. Any other malignancy unless free of disease for at least five years except for:

    1. Other HNSCC of a location as described in inclusion criterion number 1
    2. Appropriately treated superficial basal cell skin cancer
    3. Surgically cured cervical cancer in situ
    4. For Korea: endoscopically cured superficial esophageal and/or gastric cancer is allowed
  11. Known lesion or signs of brain metastasis.
  12. Known pre-existing interstitial lung disease (ILD).
  13. Clinically relevant cardiovascular abnormalities, as judged by the investigator, such as, but not limited to, uncontrolled hypertension, congestive heart failure NYHA classification =III, unstable angina, myocardial infarction within six months prior to randomization, or poorly controlled arrhythmia.
  14. Cardiac left ventricular dysfunction with resting ejection fraction <lower limit of normal (LLN) of investigational site (if no LLN is defined at the site the lower limit is 50%).
  15. Significant or recent acute gastrointestinal disorders with diarrhoea as a major symptom in the opinion of the investigator, e.g. Crohn's disease, malabsorption or CTCAE grade >1 diarrhoea of any aetiology at randomization.
  16. Known HIV, active hepatitis B, active hepatitis C, and/or other known severe infections, including but not limited to tuberculosis, as judged by the investigator.
  17. Other significant disease that in the investigator's opinion would exclude the subject from the trial.
  18. Screening laboratory values:

    1. Absolute neutrophil count (ANC) <1.5x10^9/l
    2. Platelet count <75x10^9/l
    3. Total bilirubin >1.5 times the upper limit of normal (ULN)
    4. Aspartate amino transferase (AST) or alanine amino transferase (ALT) >3 times the ULN (if related to liver metastases >5 times the ULN)
    5. Calculated creatinine clearance <50 ml/min (as evidenced by using the Cockcroft-Gault formula).
  19. Women of child-bearing potential and men who are able to father a child, unwilling to be abstinent or to use adequate contraception during the trial and for at least six months after end of treatment. Adequate methods of contraception and definition of child-bearing potential.
  20. Pregnancy or breast feeding.
  21. Known or suspected hypersensitivity to any of the study medications or their excipients.
  22. Any past or present history of areca/betel-nut chewing or its derivatives for a cumulative duration of more than 3 months
  23. Patients unable to comply with the protocol, in the opinion of the investigator.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01856478

Contacts
Contact: Boehringer Ingelheim Call Center 1-800-243-0127 clintriage.rdg@boehringer-ingelheim.com

  Show 40 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01856478     History of Changes
Other Study ID Numbers: 1200.161 
Study First Received: May 15, 2013
Last Updated: January 4, 2017
Health Authority: China: Food and Drug Administration
Egypt: Ministry of Health and Population
Hong Kong: Department of Health
India: Drugs Controller General of India
Philippines: Department of Health
South Korea: Ministry of Food and Drug Safety (MFDS)
Taiwan : Food and Drug Administration
Thailand: Food and Drug Administration

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 17, 2017