Clinical Trial: Study of Chemotherapy Prior to Radiotherapy and Chemotherapy in Patients With HPV Associated Cancer of the Oral Cavity

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Phase II Trial of Neoadjuvant Chemotherapy for HPV-Associated Squamous Cell Carcinoma of the Oropharynx Followed by Reduced Dose Radiotherapy/Chemoradiotherapy for Responders or Standard Dose Chemorad

Brief Summary: This study looks at the use of three cycles of chemotherapy given prior to radiation therapy in patients with cancer of the oral cavity and evidence of prior exposure to Human Papilloma Virus (HPV). Patients with cancer of the oral cavity who have evidence of exposure to HPV have a better prognosis than those who do not have such evidence of exposure to HPV. The main hypothesis of this study is that using three cycles of chemotherapy prior to embarking on radiation therapy will allow the use of reduced doses of radiation therapy and, therefore, less radiation induced side-effects. The primary objective is to determine the activity of this pre-radiation chemotherapy strategy along with reduced dose levels of radiation with or without chemotherapy during the radiation phase. The effectiveness of the strategy will be assessed at three months following the completion of the radiation therapy phase and also at two years following completion of the radiation therapy.

Detailed Summary:

Induction Chemotherapy TPF induction chemotherapy will be administered as published from the TAX 323 phase III trial. Specifically, each cycle will consist of docetaxel at a dose of 75 mg per square meter, administered as a 1-hour infusion on day 1, followed by cisplatin at a dose of 75 mg per square meter, administered as a 1-hour infusion on day 1, and fluorouracil at a dose of 750 mg per square meter per day, administered by continuous infusion on days 1 to 5. Induction chemotherapy will be given every 3 weeks for three cycles, unless there is distant disease progression, unacceptable toxic effects, or withdrawal of consent by the patient. All patients will be required to have a continuous venous access device such as a PICC line or Infusaport type device. This is standard of care for continuous infusion fluorouracil. Response assessment by examination, contrast-enhanced CT imaging and whole body PET-CT will be performed after the third treatment cycle. Radiotherapy or chemoradiotherapy will commence within 3-4 weeks from the conclusion of the induction program.

Selection for Radiation Alone vs. Chemoradiotherapy For CR/PR patients with CR at primary site following induction chemotherapy, locoregional therapy will be risk-adjusted according to baseline tumor stage/characteristics. Local therapy will be 1) radiotherapy as a single modality for Tx (T1-2), T0-1 or exophytic T2, N0-2a disease, or will be 2) concomitant chemoradiotherapy for Tx (T3), endophytic T2, T3, N2b-c disease. Patients with PR at primary site will receive concurrent chemotherapy and reduced dose radiation.

All SD/PD patients will receive concurrent chemotherapy and full dose radiation. Patients catalogued with disease progression on the basis of new distant metastatic disease spread (DM) during induction chemotherapy will be taken off protocol for con
Sponsor: Northwell Health

Current Primary Outcome: Response (CR+PR) Status at 3 Months Post-therapy [ Time Frame: 3 months following completion of radiation phase ]

Original Primary Outcome: Response (CR+PR) Status at 3 Months Post-therapy [ Time Frame: 3 months following completion of radiation phase ]

Current Secondary Outcome:

• To Define Objective Tumor Response Rates to Induction Chemotherapy and to Subsequent Radiation-based Treatment. [ Time Frame: Three months following completion of radiation therapy phase. ]
  To define objective tumor response rates to induction chemotherapy and to subsequent radiation-based treatment, per RESIST version 1.1 criteria.
• Progression-free Survival at 2 Years [ Time Frame: At two years following completion of radiation phase ]
  assess Progression-free survival at 2 years.
• Assess Overall Survival at 2 Years. [ Time Frame: At two years following completion of radiation phase ]
  To assess overall survival at 2 years.
• Assess Locoregional Disease Control at 2 Years [ Time Frame: At two years following completion of radiation phase ]
  To assess locoregional disease control at 2 years
• Assess Distant Disease Control at 2 Years. [ Time Frame: At two years following completion of radiation phase ]
  3.5 To assess distant disease control at 2 years.
• Assessment of Quality of Life Outcomes [ Time Frame: Baseline, during therapy and up to two years following completion of radiation phase ]
  Serial evaluation of functional quality-of-life, including M. D. Anderson Dysphagia Inventory (MDADI) and Oropharyngeal swallowing efficiency (OPSE) measures of swallowing function, as well as formal sialometric measurement of parotid function.
• Identify Additional Toxicity of Treatment [ Time Frame: During therapy and up to 5 years following completion of treatment ]
  To identify additional toxicity of treatment

Original Secondary Outcome:

• To define objective tumor response rates to induction chemotherapy and to subsequent radiation-based treatment, per RESIST version 1.1 criteria. [ Time Frame: Three months following completion of radiation therapy phase. ]
  To define objective tumor response rates to induction chemotherapy and to subsequent radiation-based treatment, per RESIST version 1.1 criteria.
• To assess progression-free survival at 2 years [ Time Frame: At two years following completion of radiation phase ]
  Progression-free survival at 2 years.
• To assess overall survival at 2 years. [ Time Frame: At two years following completion of radiation phase ]
  To assess overall survival at 2 years.
• To assess locoregional disease control at 2 years [ Time Frame: At two years following completion of radiation phase ]
  To assess locoregional disease control at 2 years
• 3.5 To assess distant disease control at 2 years. [ Time Frame: At two years following completion of radiation phase ]
  3.5 To assess distant disease control at 2 years.
• Assessment of Quality of Life Outcomes [ Time Frame: Baseline, during therapy and up to two years following completion of radiation phase ]
  Serial evaluation of functional quality-of-life, including M. D. Anderson Dysphagia Inventory (MDADI) and Oropharyngeal swallowing efficiency (OPSE) measures of swallowing function, as well as formal sialometric measurement of parotid function.
• To identify additional toxicity of treatment [ Time Frame: During therapy and up to 5 years following completion of treatment ]
  To identify additional toxicity of treatment

Information By: Northwell Health

Dates:
Date Received: February 1, 2012
Date Started: August 2010
Date Completion:
Last Updated: January 29, 2016
Last Verified: January 2016