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Summary

for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started

Description

Summary

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.

Official Title

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

Details

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

  1. 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).
  2. 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.

Keywords

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 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 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 Laryngeal Diseases Laryngeal Neoplasms Oropharyngeal Neoplasms Carcinoma, Verrucous Tongue Neoplasms Docetaxel Cisplatin Cetuximab Antibodies Immunoglobulins Antibodies, Monoclonal

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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 within 63 days of registration
  • 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 at the primary tumor resection margin(tumor or ink)
  • 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 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-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, if fulfills the chest imaging requirement.
  • Zubrod performance status of 0-1 within 14 days prior to registration
  • Absolute granulocyte count (AGC) >= 1,500 cells/mm3

  • Platelets >= 100,000 cells/mm3

  • 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 or urine 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

You CAN'T join if...

  • 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 < 3.0 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; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic
  • Prior allergic reaction to cetuximab

Locations

  • UCSF Medical Center-Mount Zion
    San Francisco, California, 94115, United States
  • Stanford Cancer Institute
    Palo Alto, California, 94304, United States
  • Sutter Cancer Centers Radiation Oncology Services-Vacaville
    Vacaville, California, 95687, United States
  • Saint Helena Hospital
    Saint Helena, California, 94574, United States
  • University of California Davis Comprehensive Cancer Center
    Sacramento, California, 95817, United States
  • Sutter General Hospital
    Sacramento, California, 95816, United States
  • Memorial Medical Center
    Modesto, California, 95355, United States
  • Mercy San Juan Medical Center
    Carmichael, California, 95608, United States
  • Sutter Cancer Centers Radiation Oncology Services-Roseville
    Roseville, California, 95661, United States
  • Sutter Cancer Centers Radiation Oncology Services-Cameron Park
    Cameron Park, California, 95682, United States
  • Sutter Cancer Centers Radiation Oncology Services-Auburn
    Auburn, California, 95603, United States
  • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    Burbank, California, 91505, United States
  • UC Irvine Health/Chao Family Comprehensive Cancer Center
    Orange, California, 92868, United States

Details

Status
in progress, not accepting new patients
Start Date
Sponsor
Radiation Therapy Oncology Group
ID
NCT01810913
Phase
Phase 2/3
Lead Scientist
Sue Yom
Study Type
Interventional
Last Updated
May 18, 2017