Clinical Trial 21657

• Overview

  Study Title:

  Randomized Phase II/III Trial of Radiation with High-Dose Cisplatin (100 mg/m2) Every Three Weeks Versus Radiation with Low-Dose Weekly Cisplatin (40 mg/m2) for Patients with Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN)

  Summary:

  This study is being done to find out if low-dose cisplatin given weekly together with radiation therapy is the same or better than high-dose cisplatin given every 3 weeks together with radiation therapy in treating patients with head and neck cancer.

  Objective:

  Primary Objectives Phase II: 1.1.1 To determine whether radiation with low-dose cisplatin weekly is superior in terms of acute toxicity, as measured by the T-scores (TAME method), to radiation with high-dose cisplatin every 3 weeks for patients with locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN). Phase III: 1.1.2 To determine whether radiation with low-dose cisplatin weekly is non-inferior to radiation with high-dose cisplatin every 3 weeks in terms of overall survival (OS) for patients with locoregionally advanced SCCHN. 1.1.3 To determine whether radiation with low-dose cisplatin weekly is superior in terms of acute toxicity, as measured by the T-scores (TAME method), to radiation with high-dose cisplatin every 3 weeks for patients with locoregionally advanced SCCHN.

• Treatments

  Therapies:

  Chemotherapy (NOS); Therapy (NOS)

  Medications:

  Aloxi (Palonosetron); Aprepitant (); Dexamethasone (); Fosaprepitant (); Granisetron (); KCL (); Mannitol (); MgSO4 (); Olanzapine (); Ondansetron (); Palonosetron (); Zofran (Ondansetron); cisplatin ()

• Inclusion Criteria

  Inclusion Criteria:
  • Pathologically (histologically or cytologically) proven diagnosis of SCCHN of the oropharynx, larynx, hypopharynx, or p16-positive unknown primary prior to registration; specimen from cervical lymph nodes with a well-defined primary site documented clinically or radiologically is acceptable; in patients with carcinoma of unknown primary this will be sufficient for pathologic confirmation without a clinically or radiographically defined primary site. For patients with oropharyngeal cancer (OPC)/cancer of unknown primary (CUP): P16 status based on local site immunohistochemical tissue staining is required. A cell block obtained from a fine needle aspiration (FNA) biopsy specimen may be used as the sole diagnostic tissue. Centers are encouraged to contact the pathology chair for clarification
  • History/physical examination within 60 days prior to registration. One of the following imaging studies is required within 60 days prior to registration: Computed tomography (CT) scan of neck (diagnostic quality with contrast, unless contraindicated) OR Magnetic resonance imaging (MRI) of the neck (diagnostic quality with contrast, unless contraindicated) OR Fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/CT of the neck; the CT component must be of diagnostic quality with contrast, unless contraindicated.
  • One of the following imaging studies is required within 60 days prior to registration: FDG-PET/CT of the chest; FDG-PET/CT scan is strongly preferred and highly recommended to be used for eligibility OR Chest CT, Exam with laryngopharyngoscopy (mirror or in office direct procedure acceptable) within 70 days prior to registration
  • Eligibility by patient cohort; (a) Non-OPC/p16-negative OPC Cohort; Tumor Site: Larynx/Hypopharynx; Clinical Staging (AJCC, 8th ed.): T3-4 N0 or T1-4 N1-3 T2 N0 (hypopharynx only) (b) Tumor Site: p16-negative OPC; Clinical Staging (AJCC, 8th ed.): T2N1, T1-4 N2-3, or T3-4 N0-1
  • p16-positive OPC/CUP Cohort; (a) Tumor Site: OPC; Smoking Status: = 10 pack-years; Clinical Staging (AJCC, 8th ed.): T1-2 N2-3 or T3-4 N0-3 (c) Tumor Site: CUP; Smoking Status: Any; Clinical Staging (AJCC, 8th ed.): T0 N2-3
  • Age >= 18
  • Zubrod (Eastern Cooperative Oncology Group [ECOG]) performance status of 0-1 within 14 days prior to registration
  • Adequate organ function as defined in protocol
  • Known human immunodeficiency virus (HIV) infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months and CD4 T Cell count > 200 cells/mm^3 are eligible for this trial. Testing is not required for entry into protocol
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes
  • Willing to use highly effective contraceptives for participants of childbearing potential (participants who may become pregnant or who may impregnate a partner) during therapy and for 14 months (females); for 11 months (males) following last dose of cisplatin; this inclusion is necessary because the treatment in this study may be significantly teratogenic
  • Other criteria apply

• Exclusion Criteria

  Exclusion Criteria:
  • Patients with oral cavity cancer, nasopharynx cancer, or p16-negative cancer of unknown primary (CUP)
  • Recurrence of the study cancer
  • Definitive clinical or radiologic evidence of distant metastatic disease
  • Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable, however, any prior exposure to cisplatin is excluded
  • 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: (a) Unstable angina requiring hospitalization in the last 6 months (b) Myocardial infarction within the last 6 months (c) New York Heart Association Functional Classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.) (d) Persistent grade 3-4 (CTCAE version 5.0) electrolyte abnormalities that cannot be reversed despite replacement as indicated by repeat testing (e) Patient must not have an active infection requiring IV antibiotics prior to registration; (f) Other chronic renal disease like nephrotic syndrome, that could be worsened by cisplatin therapy (g) History of allogenic organ transplantation (h)Any symptomatic peripheral sensory neuropathy grade >= 2 (CTCAE version 5.0);
  • Pregnancy and individuals unwilling to discontinue nursing
  • History of hypersensitivity to cisplatin or platinum-containing compounds.
  • Other exclusion may apply

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