Radiation Therapy with Cisplatin, Docetaxel, or Cetuximab and Docetaxel after Surgery in Treating Patients with High-Risk Stage III-IV Squamous Cell Head and Neck Cancer

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Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase III, Phase IIBiomarker/Laboratory analysis, TreatmentTemporarily closed18 and overRTOG-1216
NCI-2013-00500, NCT01810913

Trial Description

Summary

This randomized phase II/III trial studies how well radiation therapy works when given together with cisplatin, docetaxel or cetuximab and docetaxel after surgery in treating patients with high-risk stage III-IV head and neck cancer the begins in the thin, flat cells (squamous cell). Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cetuximab may block the growth of tumor cells by blocking a protein and many other tumor cells functions. It is not yet known whether radiation therapy is more effective when given with cisplatin, docetaxel, or cetuximab and docetaxel.

Further Study Information

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 arms.

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

ARM 2: Patients undergo IMRT as in Arm I and receive concurrent docetaxel IV over 60 minutes 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 concurrent 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.

Eligibility Criteria

Inclusion Criteria:

Pathologically (histologically or cytologically) proven diagnosis of head and neck squamous cell carcinoma (HNSCC) involving the oral cavity (excluding lips), oropharynx (p16 negative), larynx, or hypopharynx

Patients must have undergone gross total surgical resection of high-risk oral cavity, oropharynx (p16 negative), larynx, or hypopharynx within 63 days prior to registration; Note: patients may have biopsy under general anesthesia in an operating room followed by definitive ablative cancer surgery representing gross total resection; the gross total resection has to be done within 63 days prior to registration; if, however, patients have ablative resection but shortly recur or are determined to have persisting disease requiring re-resection to achieve gross total resection, then the patient is not eligible

Patients must have at least 1 of the following high-risk pathologic features: extracapsular nodal extension or invasive cancer at the primary tumor resection margin (tumor on ink)

Pathologic stage III or IV 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 84 days prior to registration;

Examination by an ear nose throat (ENT) or head & neck surgeon prior to surgery; a laryngopharyngoscopy (mirror and/or fiber optic and/or direct procedure), if appropriate, is recommended but not required; intra-operative examination is acceptable documentation

Pre-operative (op) Imaging of the head and neck: A neck computed tomography (CT) (with contrast) or CT/positron emission tomography (PET) (with contrast) and/or an magnetic resonance imaging (MRI) of the neck (T1 with gadolinium and T2) within 84 days prior to surgery; Note: this imaging data (diagnostic pre-operative scan showing gross disease) is to be submitted in Digital Imaging and Communications in Medicine (DICOM) format via TRIAD; the report is to be uploaded into Rave

Chest CT scan (with or without contrast) or CT/PET that includes the chest (with or without contrast) either within 84 days prior to surgery or within 120 days prior to registration; Note: if the CT/PET with or without contrast is done within 84 days prior to surgery, it fulfills the chest imaging requirement

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 urine or 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 (e.g., 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 and Prevention (CDC) definition; note: human immunodeficiency virus (HIV) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immuno-compromised patients

Grade 3-4 electrolyte abnormalities (Common Terminology Criteria for Adverse Events [CTCAE], version [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 (> 14 mmol/L)

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

Potassium < 3.0 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

Prior allergic reaction to cetuximab

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

NRG Oncology

  • National Cancer Institute
Paul Maurice Harari, Principal Investigator

Trial Sites

U.S.A.

Indiana
South Bend

Northern Indiana Cancer Research Consortium

Binh Nguyen Tran
Ph: 574-237-1328

Binh Nguyen Tran
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01810913

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.