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Randomized Phase II/III Trial of Surgery and Postoperative Radiation Delivered With Concurrent Cisplatin Versus Docetaxel Versus Docetaxel and Cetuximab for High-Risk Squamous Cell Cancer of the Head and Neck


Phase 2/Phase 3
18 Years
N/A
Open (Enrolling)
Both
Recurrent Metastatic Squamous Neck Cancer With Occult Primary, Recurrent Salivary Gland Cancer, Recurrent Squamous Cell Carcinoma of the Hypopharynx, Recurrent Squamous Cell Carcinoma of the Larynx, Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity, Recurrent Squamous Cell Carcinoma of the Oropharynx, Recurrent Verrucous Carcinoma of the Larynx, Recurrent Verrucous Carcinoma of the Oral Cavity, 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 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, Tongue Cancer

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Trial Information

Randomized Phase II/III Trial of Surgery and Postoperative Radiation Delivered With Concurrent Cisplatin Versus Docetaxel Versus Docetaxel and Cetuximab for High-Risk Squamous Cell Cancer of the Head and Neck


PRIMARY OBJECTIVES:

I. To select the better experimental arm to improve disease-free survival (DFS) over the
control arm of radiation and cisplatin. (Phase II) II. To determine whether the selected
experimental arm will improve overall survival (OS) over the control arm of radiation and
cisplatin. (Phase III)

SECONDARY OBJECTIVES:

I. To improve local-regional disease control. II. To compare distant metastasis. III. To
compare patterns of cancer failure (local, regional, distant) and correlate with radiation
dose and technique.

IV. To compare acute toxicity profiles during radiation therapy (RT) and at completion of
treatment.

V. To compare late toxicity profiles at 1, 3, and 5 years after treatment. VI. To compare
overall quality of life. VII. To compare patient-reported outcome. VIII. To compare
swallowing function at 1 and 2 years. IX. To investigate associations between acute mucosal
toxicity, swallowing function, and quality of life (QOL).

X. To compare quality adjusted life years (QALY). XI. To investigate associations between
late toxicity (dysphagia) and QALY. XII. To determine whether specific molecular profiles
are associated with clinical outcomes.

OUTLINE: Patients are randomized to 1 of 3 treatment groups.

ARM 1: Patients undergo intensity modulated radiation therapy (IMRT) once daily (QD) five
days a week and receive cisplatin intravenously (IV) over 1-2 hours once weekly for 6 weeks.

ARM 2: Patients undergo IMRT as in Arm I and receive docetaxel IV once weekly for 6 weeks.

ARM 3: Patients receive cetuximab IV over 120 minutes on week 1 and over 60 minutes once
weekly on weeks 2-7. Patients undergo IMRT as in Arm I and receive docetaxel once weekly for
6 weeks.

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


Inclusion Criteria:



- Pathologically (histologically or cytologically) proven diagnosis of head and neck
squamous cell carcinoma (HNSCC) involving the oral cavity, oropharynx (p16 negative),
larynx, or hypopharynx within 49 days of registration

- Patients must have undergone gross total surgical resection of high-risk oral cavity,
oropharynx (p16 negative), larynx, or hypopharynx within 49 days prior to
registration

- Patients must have at least 1 of the following high-risk pathologic features:
extracapsular nodal extension or invasive cancer seen within 3 mm of the primary
tumor resection margins

- Pathologic stage III or IV head and neck squamous cell carcinoma (HNSCC), including
no distant metastases, based upon the following minimum diagnostic workup:

- General history and physical examination by a radiation oncologist and/or
medical oncologist within 56 days prior to registration;

- Examination by an ear nose throat (ENT) or head & neck surgeon, within 56 days
prior to registration; a laryngopharyngoscopy (mirror and/or fiber optic and/or
direct procedure) is recommended but not required.

- Pre-op Imaging within 63 days of registration: Either a computed tomography (CT)
(with contrast) or CT/positron emission tomography (PET) (with contrast) and/or
an magnetic resonance imaging (MRI) (T1 with gadolinium and T2) of the head and
neck within 63 days prior to registration; note: this imaging data (diagnostic
pre-operative scan showing gross disease) is to be submitted on a compact disk
(CD) in Digital Imaging and Communications in Medicine (DICOM) format to
Radiation Therapy Oncology Group (RTOG) Headquarters with the report

- Chest CT scan (with or without contrast) or CT/PET of chest (with or without
contrast) within 56 days prior to registration

- Zubrod performance status of 0-1 within 14 days prior to registration

- Absolute granulocyte count (AGC) >= 1,500 cells/mm^3

- Platelets >= 100,000 cells/mm^3

- Hemoglobin >= 8.0 g/dl (Note: The use of transfusion or other intervention to achieve
hemoglobin [Hgb] >= 8.0 g/dl is acceptable)

- Total bilirubin < 2 x institutional upper limit of normal (ULN) within 14 days prior
to registration

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x
institutional ULN within 14 days prior to registration

- Serum creatinine institutional ULN within 14 days prior to registration or;
creatinine clearance (CC) >= 50 ml/min within 14 days prior to registration
determined by 24-hour collection or estimated by Cockcroft-Gault formula

- Negative serum pregnancy test within 14 days prior to registration for women of
childbearing potential

- The following assessments are required within 14 days prior to registration: sodium
(Na), potassium (K), chloride (Cl), glucose, calcium (Ca), magnesium (Mg), and
albumin; Note: Patients with an initial magnesium < 0.5 mmol/L (1.2 mg/dl) may
receive corrective magnesium supplementation but should continue to receive either
prophylactic weekly infusion of magnesium and/or oral magnesium supplementation (eg,
magnesium oxide) at the investigator's discretion

- Patients with feeding tubes are eligible for the study

- Women of childbearing potential and male participants who are sexually active must
agree to use a medically effective means of birth control

- Patient must provide study specific informed consent prior to study entry, including
consent for mandatory tissue submission for epidermal growth factor receptor (EGFR)
analysis and for oropharyngeal cancer patients, human papilloma virus (HPV) analysis

Exclusion Criteria:

- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
for a minimum of 1095 days (3 years); noninvasive cancers (for example, carcinoma in
situ of the breast, oral cavity, or cervix are all permissible) are permitted even if
diagnosed and treated < 3 years ago

- Patients with simultaneous primaries or bilateral tumors are excluded, with the
exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0
resected differentiated thyroid carcinoma, who are eligible

- Prior systemic chemotherapy or anti-epidermal growth factor (EGF) therapy for the
study cancer; note that prior chemotherapy for a different cancer is allowable

- Prior radiotherapy to the region of the study cancer that would result in overlap of
radiation therapy fields

- Severe, active co-morbidity, defined as follows:

- Unstable angina and/or congestive heart failure requiring hospitalization within
6 months prior to registration

- Transmural myocardial infarction within 6 months prior to registration

- Acute bacterial or fungal infection requiring intravenous antibiotics at the
time of registration

- Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy at the time of
registration

- Idiopathic pulmonary fibrosis or other severe interstitial lung disease that
requires oxygen therapy or is thought to require oxygen therapy within 1 year
prior to registration

- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
note, however, that laboratory tests for coagulation parameters are not required
for entry into this protocol

- Acquired immune deficiency syndrome (AIDS) based upon current Centers for
Disease and Control (CDC) definition; note: HIV testing is not required for
entry into this protocol; the need to exclude patients with AIDS from this
protocol is necessary because the treatments involved in this protocol may be
significantly immunosuppressive; protocol-specific requirements may also exclude
immuno-compromised patients

- Grade 3-4 electrolyte abnormalities (Common Terminology Criteria for Adverse Events
[CTCAE], v. 4):

- Serum calcium (ionized or adjusted for albumin) < 7 mg/dl (1.75 mmol/L) or > 12.5
mg/dl (> 3.1 mmol/L) despite intervention to normalize levels

- Glucose < 40 mg/dl (< 2.2 mmol/L) or > 250 mg/dl (> 14mmol/L)

- Magnesium < 0.9 mg/dl (< 0.4 mmol/L) or > 3 mg/dl (> 1.23 mmol/L) despite
intervention to normalize levels

- Potassium < 3.5 mmol/L or > 6 mmol/L despite intervention to normalize levels

- Sodium < 130 mmol/L or > 155 mmol/L despite intervention to normalize levels

- Pregnancy or women of childbearing potential and men who are sexually active and not
willing/able to use medically acceptable forms of contraception; this exclusion is
necessary because the treatment involved in this study may be significantly
teratogenic

- Prior allergic reaction to cetuximab

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Disease-free survival (DFS) (Phase II)

Outcome Description:

Estimated using the Kaplan-Meier method for each arm. Their distributions will be compared between treatment arms with a one-sided log rank test.

Outcome Time Frame:

Up to 8 years

Safety Issue:

No

Principal Investigator

Paul Harari

Investigator Role:

Principal Investigator

Investigator Affiliation:

Radiation Therapy Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

RTOG 1216

NCT ID:

NCT01810913

Start Date:

March 2013

Completion Date:

Related Keywords:

  • Recurrent Metastatic Squamous Neck Cancer With Occult Primary
  • Recurrent Salivary Gland Cancer
  • Recurrent Squamous Cell Carcinoma of the Hypopharynx
  • Recurrent Squamous Cell Carcinoma of the Larynx
  • Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Recurrent Squamous Cell Carcinoma of the Oropharynx
  • Recurrent Verrucous Carcinoma of the Larynx
  • Recurrent Verrucous Carcinoma of the Oral Cavity
  • 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 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
  • Tongue Cancer
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Neoplasms, Squamous Cell
  • Head and Neck Neoplasms
  • Laryngeal Diseases
  • Tongue Neoplasms
  • Carcinoma, Verrucous
  • Neoplasms, Unknown Primary
  • Salivary Gland Neoplasms
  • Hypopharyngeal Neoplasms
  • Laryngeal Neoplasms
  • Oropharyngeal Neoplasms

Name

Location

Stanford University Medical CenterStanford, California  94305-5408
University of Wisconsin HospitalMadison, Wisconsin  53792