De-intensification of Radiation & Chemotherapy in Low-Risk Human Papillomavirus-related Oropharyngeal Squamous Cell Ca
Condition: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Oropharyngeal Neoplasms
MeSH terms: Carcinoma; Neoplasms; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck; Oropharyngeal Neoplasms
Intervention: Intensity Modulated Radiotherapy (IMRT); Cisplatin; Limited surgical evaluation
Intervention description: All patients will receive IMRT. Dose painting IMRT will be used and all doses will be specified to the planning target volume (PTV). The high risk planning target volume (PTV-HR) and standard risk planning target volume (PTV-SR) will be treated to the following respective total doses: 60 Gy and 54 Gy. The dose per fraction to the PTV-HR and PTV-SR will be 2 Gy per day and 1.8 Gy per day, respectively. The PTV-HR will include the gross tumor and the PTV-SR will include the lymph nodes at risk for harboring micro-metastatic disease (i.e. subclinical disease).; Cisplatin, 30mg/m2, will be given intravenously over 60 minutes weekly during IMRT; 6 total doses for a total of 180 mg/m2. It is preferred that the doses be administered on days 1, 8, 15, 22, and 29, and 36 of IMRT; however, this is not mandatory.; 4 to 14 weeks after completion of CRT, patients will have at least a biopsy of the primary tumor and limited neck surgery to remove those lymph nodes that were involved with cancer prior to CRT.
Intervention MeSH terms: Cisplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Human Papilloma Virus; Oropharynx; Oropharyngeal Squamous Cell Carcinoma; Squamous Cell Carcinoma; Radiation Therapy; Chemotherapy; p16

Summary:

      The purpose of this research study is to learn about the effectiveness of using
      lower-intensity radiation and chemotherapy to treat human papillomavirus (HPV) associated
      low-risk oropharyngeal and/or unknown primary squamous cell carcinomas of the head and neck.
      The cure rate for this type of cancer is estimated to be high, > 90%. The standard treatment
      for this cancer is 7 weeks of radiation with 3 high doses of cisplatin. Sometimes surgery is
      performed afterwards. This standard regimen causes a lot of side effects and long term
      complications. This study is evaluating whether a lower dose of radiation and chemotherapy
      may provide a similar cure rate as the longer, more intensive standard regimen. Patients in
      this study will receive 1 less week of radiation and a lower weekly dose of chemotherapy
      followed by a limited surgical evaluation.
    

Eligibility criteria:

        Inclusion Criteria:

          1. ≥ 18 years of age

          2. T0-3, N0 to N2c, M0 squamous cell carcinoma of the oropharynx

          3. Biopsy proven squamous cell carcinoma that is HPV and/or p16 positive

          4. ≤ 10 pack-years smoking history or > 5 years of abstinence from smoking

          5. History/physical examination within 8 weeks prior to registration

          6. Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks
             prior to registration.

          7. The Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1

          8. Complete Blood Count (CBC)/differential obtained within 4 weeks prior to registration,
             with adequate bone marrow function defined as follows: Absolute neutrophil count (ANC)
             ≥ 1,800 cells/mm3; Platelets ≥ 100,000 cells/mm3; Hemoglobin ≥ 8.0 g/dl.

          9. Adequate renal and hepatic function within 4 weeks prior to registration, defined as
             follows: Serum creatinine < 2.0 mg/dl; Total bilirubin < 2 x the institutional upper
             limit of normal (ULN); aspartate aminotransferase (AST) or alanine aminotransferase
             (ALT) < 3 x the institutional ULN.

         10. Negative serum pregnancy test within 2 weeks prior to registration for women of
             childbearing potential.

         11. Women of childbearing potential and male participants who are sexually active must
             practice adequate contraception during treatment and for 6 weeks following treatment.

         12. Patients must be deemed able to comply with the treatment plan and follow-up schedule.

         13. Patients must provide study specific informed consent prior to study entry.

        Exclusion Criteria:

          1. Prior history of radiation therapy to the head and neck

          2. Prior history of head and neck cancer.

          3. Severe, active co-morbidity, 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 at the time of registration; Hepatic insufficiency
             resulting in clinical jaundice and/or coagulation defects; Note, however, coagulation
             parameters are not required for entry into this protocol; Pre-existing ≥ grade 2
             neuropathy; Prior organ transplant.

          4. Known HIV positive

          5. Significant pre-existing hearing loss, as defined by the patient or treating
             physician.