Clinical Trial: Radiation Therapy With or Without Cisplatin in Treating Patients With Stage III-IV Squamous Cell Carcinoma of the Head and Neck Who Have Undergone Surgery

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase II Randomized Trial of Adjuvant Radiotherapy With or Without Cisplatin for p53 Mutated, Surgically Resected Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Brief Summary: This phase II trial studies how well radiation therapy with or without cisplatin works in treating patients with stage III-IV squamous cell carcinoma of the head and neck who have undergone surgery. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known if radiation therapy is more effective with or without cisplatin in treating patients with squamous cell carcinoma of the head and neck.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To evaluate the disease-free survival (DFS) of patients with stage III-IV squamous cell carcinoma of the head and neck (SCCHN) and disruptive p53 mutations after primary surgical resection followed by postoperative radiotherapy (PORT) alone or PORT with concurrent cisplatin.

SECONDARY OBJECTIVES:

I. To evaluate the DFS of patients with stage III-IV SCCHN and non-disruptive p53 mutations after primary surgical resection followed by PORT alone or PORT with concurrent cisplatin.

II. To evaluate the DFS of patients with stage III-IV SCCHN and p53 wild type after primary surgical resection followed by PORT alone or PORT with concurrent cisplatin.

III. To evaluate toxicities of PORT alone or PORT with concurrent cisplatin. IV. To evaluate p53 mutation as a predictive biomarker of survival benefit given post-operative concurrent radiation and cisplatin.

V. To identify potential genomic alterations in addition to TP53 mutations that may be developed to a novel treatment approach.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients undergo intensity-modulated radiation therapy (IMRT) once daily (QD) 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.

ARM B: Patients undergo IMRT QD 5 days a week and receive cisplatin intravenously (IV) over 1-2 hours weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study
Sponsor: ECOG-ACRIN Cancer Research Group

Current Primary Outcome: DFS in patients with disruptive p53 mutation [ Time Frame: Date of randomization to the date of recurrence, second primary tumor from the head and neck region, or death, assessed up to 10 years ]

Kaplan-Meier estimates will be used to estimate event-time distributions and comparison between arms will be performed using a log-rank test.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • DFS in patients with non-disruptive p53 mutation [ Time Frame: Date of randomization to the date of recurrence, second primary tumor from the head and neck region, or death, assessed up to 10 years ]
    Kaplan-Meier estimates will be used to estimate event-time distributions and comparison between arms will be performed using a log-rank test.
  • DFS in patients with wild type p53 mutation [ Time Frame: Date of randomization to the date of recurrence, second primary tumor from the head and neck region, or death, assessed up to 10 years ]
    Kaplan-Meier estimates will be used to estimate event-time distributions and comparison between arms will be performed using a log-rank test.
  • Incidence of adverse events graded using Common Terminology Criteria for Adverse Events version 4 [ Time Frame: Up to 6 weeks ]
    Toxicity will be examined by arm and compared using the Fisher's exact test.
  • p53 as a predictive marker of recurrence [ Time Frame: Baseline ]
    To evaluate whether p53 is a predictive marker, a p53 by treatment arm interaction term will be tested in a Cox proportional hazards model.


Original Secondary Outcome: Same as current

Information By: Eastern Cooperative Oncology Group

Dates:
Date Received: April 6, 2016
Date Started: March 2016
Date Completion:
Last Updated: October 4, 2016
Last Verified: October 2016