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Title   Randomized Phase II/III Trial of Surgery and Postoperative Radiation Delivered with Concurrent Cisplatin Versus Docetaxel and Cetuximab for High-Risk Squamous Cell Cancer of the Head and Neck
Study Number   R1216
Trial Type   Oncology-Head and Neck
Trial Status   Open to Accrual
Date Posted   06/28/2013
Principal Investigator   Marshall Levine¸ MD
Contact Name   Jennifer Lippy
Phone   (443) 849-8089
Alternate Phone   (443) 849-8058
Fax   (443) 849-3777
Description  

Current Primary Outcome Measures
                                     - Disease-free survival (DFS)

                                     - Overall survival (OS)

This randomized phase II/III trial studies how well radiation therapy works when given together with cisplatin compared to docetaxel or cetuximab and docetaxel after surgery in treating patients with stage III-IV squamous cell head and neck cancer. 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. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or transmit tumor killing molecules to them. It is not yet known whether radiation therapy is more effective when given with cisplatin, docetaxel, or cetuximab and docetaxel.

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)

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/Notes  


Estimated Primary Completion Date: May 2020

Eligibility Criteria:

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

- 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

- 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:

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

          º 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.

          º 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

          º 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:

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

          º Transmural myocardial infarction within 6 months prior to registration

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

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

          º 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

          º 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

          º 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

Gender: Both
Ages: 18 Years and older
Accepts Healthy Volunteers: No
Location Countries: United States

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