Clinical Trial 17425

• Overview

  Study Title:

  Randomized Phase II/III Trial of Adjuvant Radiation Therapy with Cisplatin, Docetaxel-Cetuximab, or Cisplatin-Atezolizumab in Pathologic High-Risk Squamous Cell Cancer of the Head and Neck

  Summary:

  First part of the study: The purpose of this part of the study is to find out what effects, good and/or bad, one of the following treatments has on you and your cancer. In this part of the study, you will receive one of the following treatments: - Standard treatment: radiation therapy and the drug cisplatin - Experimental treatment: radiation therapy and the drug docetaxel - Experimental treatment: radiation therapy and the drugs docetaxel and cetuximab Second part of the study: The purpose of this part of this study is to compare the effects, good and/or bad, of the standard treatment (radiation therapy and cisplatin) with one of the experimental treatments chosen from the first part of the study (either radiation therapy + docetaxel or radiation therapy + cetuximab + docetaxel) to find out which is better. In this part of the study, participants will get either the standard treatment or the experimental treatment.

  Objective:

  Randomized Phase II Component Primary Objective: to select the better experimental arm to improve disease-free survival (DFS) over the control arm of radiation and cisplatin Phase III Component Primary Objective: to determine whether the selected experimental arm will improve overall survival (OS) over the control arm of radiation and cisplatin Randomized Phase II and Phase III Components Secondary Objectives 1 To improve local-regional disease control; 2 To compare distant metastasis; 3 To compare patterns of cancer failure (local, regional, distant) and correlate with radiation dose and technique; 4 To compare acute toxicity profiles during RT and at completion of treatment; 5 To compare late toxicity profiles at 1, 3, and 5 years after treatment; 6 To compare overall quality of life; 7 To compare patient-reported outcome; 8 To compare swallowing function at 1 and 2 years; 9 To investigate associations between acute mucosal toxicity, swallowing function, and QOL; 10 To compare quality adjusted life years (QALY); 11 To investigate associations between late toxicity (dysphagia) and QALY; 12 To determine whether specific molecular profiles are associated with clinical outcomes.

• Treatments

  Therapies:

  Chemotherapy (NOS); Immunotherapy; Radiotherapy

  Medications:

  Atezolizumab (Tecentriq); Cetuximab (); Erbitux (Cetuximab); Taxotere (docetaxel); cisplatin (); docetaxel ()

• Inclusion Criteria

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  • 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
  • Must have undergone gross total surgical resection of high-risk oral cavity, oropharynx (p16 negative), larynx, or hypopharynx within 63 days prior to registration
  • 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 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 CT (with contrast) or CT/PET (with contrast) and/or an MRI of the neck (T1 with Gadolinium and T2) within 84 days prior to surgery. 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.
  • Zubrod performance status of 0-1 within 14 days prior to registration
  • CBC/differential obtained within 14 days prior to registration on study, with adequate bone marrow function
  • Adequate hepatic function
  • Adequate renal function
  • 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 > 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

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  • 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 > 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) 12.5 mg/dl (> 3.1 mmol/L) despite intervention to normalize levels
  • Glucose 250 mg/dl (> 14mmol/L)
  • Magnesium 3 mg/dl (> 1.23 mmol/L) despite intervention to normalize levels
  • Potassium 6 mmol/L despite intervention to normalize levels
  • Sodium 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

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