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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


Phase 2
18 Years
N/A
Not Enrolling
Both
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

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Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Outcome Measure:

DFS

Outcome Description:

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.

Outcome Time Frame:

From randomization to the earlier of disease recurrence, second primary cancer, or death without recurrence, assessed up to 5 years

Safety Issue:

No

Principal Investigator

Christine Chung

Investigator Role:

Principal Investigator

Investigator Affiliation:

Eastern Cooperative Oncology Group

Authority:

United States: Institutional Review Board

Study ID:

E1311

NCT ID:

NCT01824823

Start Date:

February 2013

Completion Date:

Related Keywords:

  • 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
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Laryngeal Diseases
  • Recurrence
  • Tongue Neoplasms
  • Carcinoma, Verrucous
  • Head and Neck Neoplasms
  • Neoplasms, Unknown Primary
  • Salivary Gland Neoplasms
  • Hypopharyngeal Neoplasms
  • Laryngeal Neoplasms
  • Oropharyngeal Neoplasms

Name

Location

Eastern Cooperative Oncology GroupBoston, Massachusetts  02215