Details

Details

Title RANDOMIZED PHASE II TRIAL OF TRANSORAL ENDOSCOPIC HEAD AND NECK SURGERY FOLLOWED BY RISK-BASED IMRT AND WEEKLY CISPLATIN VERSUS IMRT AND WEEKLY CISPLATIN FOR HPV NEGATIVE OROPHARYNX CANCER

IRB RTOG1221

CC 14-225

Hospital Main Campus

Phase Phase 2

Disease Head and Neck

Drug Cisplatin

Description

Description

Primary Objective

  1. To determine if primary treatment with transoral endoscopic head and neck surgery will improve PFS for patients with HPV- OPC.

Secondary Objectives (10/2/13)

  1. To compare patterns of failure (local-regional relapse versus distant) and survival (overall and progression-free)
  2. To determine the safety and efficacy (rate of positive surgical margins) of using transoral robotic surgery for patients with HPV-negative tumors of the tonsil, tongue-base, or glossopharyngeal sulcus
  3. To compare head and neck cancer-specific quality of life (QOL) short-term (< 6 months) and long-term (2 years) relating to swallowing function
  4. To compare subjective (patient reported) and objective (physiologic) measures of swallowing function short-term and long-term
  5. To assess effect of neck dissection on shoulder function using a validated QOL instrument for patients undergoing neck dissection
  6. To assess the correlation of physician derived CTV�s with locoregional control or failure
  7. To determine whether specific molecular profiles are associated with overall or progression-free survival or other clinical endpoints
  8. To determine the sensitivity and specificity of pre-treatment CT scans detecting the presence of lymph node extracapsular extension by examining the surgically dissected lymph nodes
Inclusion Criteria

Inclusion Criteria

Patient Eligibility

  1. Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma of the oropharynx, localized to the tonsil, glossopharyngeal sulcus, and tongue-base within 6 weeks (42 days) of registration
  2. The primary tumor must be resectable through a transoral endoscopic head and neck surgery with anticipation of resection free margins (resection does not require total or subtotal glossectomy or total laryngectomy) Specifically, patients must (1) not have trismus, (2) not have nor surrounding soft-tissue margins, regardless of etiology.
  3. Clinical stage III-IV; T1-2, N1-2b; with tumors not approaching within 1 cm of midline, and amenable to transoral eHNS
  4. p16 negative by immunohistochemistry (documented by the institution�s pre-enrollment biomarker screening at a CLIA-certified lab), defined as absent, weak, and only focal nuclear and cytoplasmic staining in less than 70% of the tumor cells (Begum 2003)
  5. Appropriate stage for protocol entry, including no distant metastases or adenopathy below the clavicles, based upon the following minimum diagnostic workup:
    • History/physical examination by the treating physician (Radiation Oncologist, Medical Oncologist, or Head and Neck Surgeon) within 30 days prior to registration
    • Imaging of the head and neck (CT with contrast, PET/CT, and/or MRI) within 30 days prior to registration. A CT scan with contrast is mandatory (unless contraindicated, e.g. contrast allergy, etc.). Note that a PET/CT scan alone (unless performed with contrast) is not sufficient.
    • Chest CT scan (with or without contrast) or PET/CT of chest (with or without contrast) within 30 days prior to registration
    • Modified barium swallow (MBS) to assess swallowing function within 30 days prior to registration
    • Preoperative Mallampatti assessment as documented by attending surgeon within 30 days prior to registration (Appendix VII)
  6. Zubrod Performance Status 0-1 within 30 days prior to registration
  7. Age ≥ 18
  8. Adequate bone marrow function within 30 days prior to registration on study, defined as follows:
    • Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3 based upon CBC/differential;
    • Platelets ≥ 100,000 cells/mm3 based upon CBC/differential;
    • Hemoglobin ≥ 8.0 g/dl based upon CBC/differential (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.)
  9. Adequate hepatic function within 30 days prior to registration on study, defined as follows:
    • Total Bilirubin ≤ 2 mg/dl;
    • AST or ALT < 3x the upper limit of normal.
  10. Adequate renal function within 30 days prior to registration, defined as follows:
    • Serum creatinine ≤ 1.5 mg/dl and/or creatinine clearance (CC) ≥ 50 ml/min; CC can be determined by 24-hour collection or estimated by Cockcroft-Gault formula:
      • CCr male = [(140 - age) x (wt in kg)]
        • [(Serum Cr mg/dl) x (72)]
      • CCr female = 0.85 x (CrCl male)
  11. Serum pregnancy test within 14 days prior to registration for women of childbearing potential
  12. Women of childbearing potential and male participants who are sexually active must practice medically effective contraception during treatment and for 42 days following completion of treatment.
  13. Patient must be able to provide study-specific informed consent prior to study entry.
Exclusion Criteria

Exclusion Criteria

Patient Ineligibility

  1. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days [3 years] (For example, carcinoma in situ of the breast or cervix are all permissible)
  2. Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a differentcancer is allowable; see Section 3.2.1.
  3. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
  4. Severe, active co-morbidity, defined as follows:
    • >2 based on the American Society of Anesthesiologists (ASA) physical status classification system (see Appendix IV);
    • 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 before registration;
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
    • Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note, however, that 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.
  5. 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.
  6. Prior allergic reaction to cisplatin
  7. 3.2.7 Radiographic evidence of retropharyngeal metastasis