A Study of Decreasing Radiation Therapy and Chemotherapy in People With Head and Neck Cancer

A Pilot Study of Radiation De-Escalation for p16 Negative Oropharyngeal Cancer and p16-Negative or Positive Laryngeal and Hypopharyngeal Cancers

The purpose of this study is to test the treatment approach of de-escalated radiation and chemotherapy followed by a planned neck dissection surgery in people with head and neck cancer. The study will look at how effective the treatment approach is against participants' cancer.

Inclusion Criteria:

• Histologically confirmed diagnosis of SCC of the head and neck (excluding nasopharynx, nasal cavity/paranasal sinus, oral cavity, salivary, thyroid, and cutaneous primary malignancies).

  • Any unknown primary SCC of the head and neck with radiographically detectable gross nodes is allowed (core or excisional biopsy acceptable; if excisional biopsy is performed, there must be residual radiographically detectable nodal disease; FNA may be acceptable only with PI and/or co-PI approval)
  • If the primary site is oropharynx or unknown primary, P16 IHC must be negative.
  • If the primary site is hypopharynx or larynx, any P16 status is acceptable (positive, negative, or unknown). P16 IHC is strongly encouraged when possible.

• Clinical stage T0-3 N1-2C M0 (AJCC 7th edition) without evidence of distant metastasis based on staging FDG PET/CT.

• 18 years of age or older.

• Must not have received prior radiation therapy or chemotherapy for HNC.

• Patients who have had their primary site tumor removed by surgery but still have residual grossly enlarged, radiographically detectable lymph nodes are eligible for this study.

• Karnofsky Performance Status (KPS) ≥ 70.

• CT or MRI of the Neck with and without contrast

  o Note: A CT scan of the Neck and/or a PET/CT performed for the purposes of radiation planning may serve as planning tools.

• Adequate hematologic function within 30 days prior to registration, defined as follows:

  • White Blood Count (WBC) ≥ 2,000 cells/µL
  • Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3
  • Platelets ≥ 100,000 cells/mm3
  • Hemoglobin ≥ 8.0 g/dL; Note: The use of transfusion or other interventions to achieve Hgb ≥ 8.0 g/dL is acceptable

• Adequate renal function within 30 days prior to registration, defined as follows:

  • Serum creatinine < 1.5 mg/dL or creatinine clearance (CrCl) ≥ 50 mL/min determined by 24-hour collection or estimated by Cockcroft-Gault formula: CrCl male = [(140 - age) x (weight in kg)] / [(Serum Cr mg/dL) x (72)] CrCl female = 0.85 x (CrCl male)
  • Patients with serum creatinine > 1.5 mg/dL can be eligible for carboplatin-based chemotherapy with approval of co-PI (Dr. Eric Sherman

• Adequate hepatic function within 30 days prior to registration, defined as follows:

  • Bilirubin < 2 mg/dL
  • AST or ALT < 3 x the upper limit of normal

• Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential.

• The subject/legally authorized representative (LAR) must provide study-specific informed consent prior to study entry.

Exclusion Criteria:

• All nasopharyngeal, nasal cavity/paranasal sinus, oral cavity, salivary gland, thyroid, and cutaneous primary malignancies.

• Any N3 patients

• Any prior radiotherapy to the head and neck region.

• Any prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different non-H&N cancer is permissible.

• Prior chemotherapy or radiotherapy within the last three years.

• Patients who underwent previous surgical resection for the same disease (except for biopsy or surgery removing primary site tumor but still present with grossly enlarged, radiographically detectable lymph nodes).

• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for 3 years or if cure rate from treatment at 5 years estimated to be ≥ 90%.

• Subjects with simultaneous primary cancers outside of the oropharynx

  o Note: Exceptions can be made for patients with simultaneous primaries outside the H&N if determined by the PI/Co-PI that the patient can proceed with protocol activities.

• Pregnant (confirmed by serum b-HCG in women of reproductive age) or breastfeeding.

• Severe, active co-morbidities defined as follows:

  • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months.
  • Transmural myocardial infarction within the last 6 months.
  • 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 within 30 days of registration.
  • Hepatic Insufficiency resulting in clinical jaundice and/or coagulation defects.