De-intensification of Radiation and Chemotherapy for Low-Risk HPV-related Oropharyngeal SCC: Follow-up Study
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 (or alternative); Assessment for surgical evaluation
Intervention description: All patients will receive Intensity Modulated Radiotherapy Treatments (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 areas at risk for harboring subclinical microscopic disease.; Cisplatin is the preferred mandated first choice chemotherapy, however alternative weekly regimens are permissible. Justification for not using cisplatin must be documented. Chemotherapy will be given intravenously weekly during IMRT. 6 total doses will be given. It is preferred that the doses be administered on days 1, 8, 15, 22, 29, and 36; however, this is not mandatory. Chemotherapy will not be given to patients with T0-2 N0-1 disease, ≤ 10 pack years smoking history.; Decisions for surgical evaluation will be based on the results of the PET/CT 10 to 16 weeks after CRT and clinical exam (including fiberoptic laryngoscopy) at that time. Other optional imaging studies may be performed. Patients with a positive PET/CT scan will undergo surgical evaluation at the discretion of the surgeon, with the goal being to remove any suspected residual tumor with a negative resection margin while maintaining organ preservation. This may include biopsies and/or oncological resections of the primary tumor and lymph node metastases. Patients with a negative PET/CT scan will be observed.
Intervention MeSH terms: Cisplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 115.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Human Papillomavirus; 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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. ≥ 18 years of age (no upper age limit)

          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 ≤ 30 pack-years smoking history WITH ≥ 5 years
             abstinence from smoking

          5. Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks
             prior to treatment

          6. ECOG Performance Status 0-1

          7. CBC/differential obtained within 8 weeks prior to treatment, with adequate bone marrow
             function defined as follows: Platelets ≥ 100,000 cells/mm3; Hemoglobin ≥ 8.0 g/dl.

          8. 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 ULN;
             AST or ALT < 3 x the institutional ULN.

          9. Negative serum pregnancy test within 2 weeks prior to registration for women of
             childbearing potential

         10. Women of childbearing potential and male participants who are sexually active must
             practice adequate contraception during treatment and for 6 weeks following treatment.

         11. Patients must be deemed able to comply with the treatment plan and follow-up schedule.

         12. 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. Unresectable disease (e.g. immobile node on physical exam, nodal disease that
             radiographically involves the carotid arteries, nerves)

          4. Currently taking Disease Modifying Rheumatoid Drugs (DMRDs)

          5. 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; Systemic lupus; Psoriatic arthritis.

          6. Known HIV positive.