Afatinib After Chemoradiation and Surgery in Treating Patients With Stage III-IV Squamous Cell Carcinoma of the Head and Neck at High-Risk of Recurrence

This study is currently recruiting participants.
Verified January 2014 by Eastern Cooperative Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT01824823
First received: April 2, 2013
Last updated: February 4, 2014
Last verified: January 2014
  Purpose

This randomized phase II trial studies how well giving afatinib after chemoradiation and surgery works in treating patients with stage III-IV squamous cell carcinoma of the head and neck at high-risk of recurrence. Afatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma
Salivary Gland Squamous Cell Carcinoma
Stage III Salivary Gland Cancer
Stage III Squamous Cell Carcinoma of the Hypopharynx
Stage III Squamous Cell Carcinoma of the Larynx
Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage III Squamous Cell Carcinoma of the Oropharynx
Stage III Verrucous Carcinoma of the Larynx
Stage III Verrucous Carcinoma of the Oral Cavity
Stage IV Squamous Cell Carcinoma of the Hypopharynx
Stage IV Squamous Cell Carcinoma of the Larynx
Stage IVA Salivary Gland Cancer
Stage IVA Squamous Cell Carcinoma of the Larynx
Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IVA Squamous Cell Carcinoma of the Oropharynx
Stage IVA Verrucous Carcinoma of the Larynx
Stage IVA Verrucous Carcinoma of the Oral Cavity
Stage IVB Salivary Gland Cancer
Stage IVB Squamous Cell Carcinoma of the Larynx
Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IVB Squamous Cell Carcinoma of the Oropharynx
Stage IVB Verrucous Carcinoma of the Larynx
Stage IVB Verrucous Carcinoma of the Oral Cavity
Stage IVC Salivary Gland Cancer
Stage IVC Squamous Cell Carcinoma of the Larynx
Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IVC Squamous Cell Carcinoma of the Oropharynx
Stage IVC Verrucous Carcinoma of the Larynx
Stage IVC Verrucous Carcinoma of the Oral Cavity
Tongue Cancer
Drug: afatinib
Other: placebo
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Placebo Controlled Phase II Trial of Afatinib (BIBW2992) as Adjuvant Therapy Following Chemoradiation in Patients With Head and Neck Squamous Cell Carcinoma at High Risk of Recurrence

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • DFS [ Time Frame: From randomization to the earlier of disease recurrence, second primary cancer, or death without recurrence, assessed up to 5 years ] [ Designated as safety issue: No ]
    Kaplan-Meier estimates will be calculated, along with their corresponding 95% confidence intervals (CIs). Comparison between arms will be performed via the log-rank test.


Secondary Outcome Measures:
  • Recurrence rate defined as the proportion of patients with disease recurrence among all eligible and treated patients [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    The exact binomial 90% confidence interval of the recurrence rate will be computed for each arm and compared by Fisher's exact test.

  • Recurrent pattern [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    The site of recurrence will be summarized by frequency/percentage for each arm. Difference in the recurrence pattern between arms will be compared using Fisher's exact test.

  • Development of second primary malignancies [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    For each arm, second primary cancer will be summarized by frequency/percentage for each cancer type. Difference in the development of second primary cancer between arms will be compared using Fisher's exact test.

  • OS [ Time Frame: From randomization onto the study to death from any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    Kaplan-Meier estimates will be used for event-time distributions (by arm) with differences assessed by the log-rank test.

  • Toxicity using Common Terminology Criteria for Adverse Events (CTCAE) version 4 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Frequency and percentage will be used to report incidence for each toxicity type (by arm). Difference in toxicity incidence between arms will be evaluated using Fisher's exact test.


Estimated Enrollment: 108
Study Start Date: July 2013
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (afatinib)
Patients receive afatinib PO QD on days 1-28.
Drug: afatinib
Given PO
Other Names:
  • BIBW 2992
  • dual tyrosine kinase inhibitor BIBW 2992
  • EGFR/HER2 TKI BIBW 2992
  • EGFR/HER2 tyrosine kinase inhibitor BIBW 2992
Other: laboratory biomarker analysis
Correlative studies
Placebo Comparator: Arm II (placebo)
Patients receive placebo PO QD on days 1-28.
Other: placebo
Given PO
Other Name: PLCB
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Examine disease-free survival (DFS) given afatinib/placebo adjuvant therapy in patients with viable tumors in lymph nodes after neck dissection for suspected residual disease after concurrent chemoradiation.

SECONDARY OBJECTIVES:

I. Evaluate the recurrence rate, recurrence patterns, development of second primary malignancies, overall survival (OS) and toxicity of afatinib/placebo.

II. Evaluate on-target inhibition by afatinib, and determine circulating deoxyribonucleic acid (DNA) as a biomarker of afatinib resistance.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive afatinib orally (PO) once daily (QD) on days 1-28.

ARM II: Patients receive placebo PO QD on days 1-28.

In both Arms, treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 1 year and then every 12 months for 1 year.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Patients must have pathological evidence of persistent lymph node disease with viable tumor cells following primary concurrent chemoradiotherapy of locoregionally advanced (stage III/IV) head and neck squamous cell carcinoma (HNSCC) of the oral cavity, oropharynx, larynx, or hypopharynx; persistent lymph node disease with viable tumor cells will be determined by the histological determination of tumor viability defined as tumor cells with intact cellular compartments (i.e. cytoplasm and nucleus) that do not exhibit karyolysis, pyknosis, or karyorrhexis on hematoxylin and eosin (H&E) staining
  • Patients must have undergone a neck dissection following completion of chemoradiotherapy and must have involved at the minimum a compartment dissection of nodal levels with residual abnormalities on post-treatment imaging studies
  • Patients must have achieved a complete response at the primary disease site after chemoradiotherapy
  • All persistent lymph node disease must have received at least 66 Gy of radiotherapy and must have been completely surgically resected prior to registration, and surgical incisions should be adequately healed
  • Patients with extracapsular lymph node extension will be eligible
  • Patients must be at least 6 weeks (42 days) and no more than 16 weeks (112 days) from completion of chemoradiation at the time of registration
  • Patients will be eligible regardless of ability to swallow; patients with dysphagia may have afatinib/placebo administered via gastrostomy tube
  • Absolute neutrophil count >= 1,000/mm^3
  • Platelets >= 100,000/mm^3
  • Total bilirubin =< 1.5 x the upper limit of normal (ULN)
  • Aspartate amino transferase (AST) =< 3 x the ULN
  • Alanine amino transferase (ALT) =< 3 x the ULN
  • Calculated creatinine clearance must be >= 50 ml/min using the Cockcroft-Gault formula
  • Patients with known persistent disease at the primary mucosal site (even if resected after chemoradiotherapy), distant metastatic disease or with any gross residual disease following neck dissection will not be eligible
  • Patients with known hypersensitivity to afatinib or any of the excipients of this product will be excluded
  • Prior cetuximab or any epidermal growth factor receptor (EGFR) inhibitors will not be permitted including cetuximab administered with a chemoradiotherapy or radiotherapy regimen
  • As all patients in this study will have received prior full dose, curative-intent external-beam radiotherapy to the involved neck, no additional external-beam radiotherapy will be permitted prior to or during study participation
  • No prior adjuvant chemotherapy (aside from the initial induction chemotherapy followed by chemoradiotherapy or chemoradiotherapy regimen) will be permitted
  • Patients with history of acute myocardial infarction within 3 months prior to registration, and any history of uncontrolled angina, uncontrolled arrhythmia, or uncontrolled heart failure will be excluded
  • Women must not be pregnant or breast-feeding due to potential harm to the fetus and baby by afatinib; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception
  • Patients with active infections, other cancers, or history of other cancers will be excluded
  • Patients participating in any other clinical trials or taking any other experimental medications will be excluded
  • Patients must have electrocardiogram (ECG) within 8 weeks prior to randomization to the study
  • Patients must be assessed for cardiac function by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) within 8 weeks prior to randomization
  • Patients with left ventricular dysfunction will be excluded
  • Patients with evidence of interstitial lung disease will be excluded
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01824823

Locations
United States, Massachusetts
Eastern Cooperative Oncology Group Recruiting
Boston, Massachusetts, United States, 02215
Contact: Christine H. Chung    410-614-6204    cchung11@jhmi.edu   
Principal Investigator: Christine H. Chung         
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Principal Investigator: Christine Chung Eastern Cooperative Oncology Group
  More Information

No publications provided

Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT01824823     History of Changes
Other Study ID Numbers: E1311, NCI-2013-00357, U10CA021115
Study First Received: April 2, 2013
Last Updated: February 4, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Laryngeal Diseases
Carcinoma
Carcinoma, Squamous Cell
Recurrence
Tongue Neoplasms
Carcinoma, Verrucous
Head and Neck Neoplasms
Neoplasms, Unknown Primary
Salivary Gland Neoplasms
Hypopharyngeal Neoplasms
Laryngeal Neoplasms
Oropharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Disease Attributes
Pathologic Processes
Mouth Neoplasms
Neoplasms by Site
Mouth Diseases
Stomatognathic Diseases
Tongue Diseases
Neoplasm Metastasis
Neoplastic Processes
Salivary Gland Diseases
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms

ClinicalTrials.gov processed this record on April 17, 2014