Phase II Randomized Trial of Radiotherapy With or Without Cisplatin for Surgically Resected Squamous Cell Carcinoma of the Head and Neck (SCCHN) With TP53 Sequencing
Overview
- Phase
- Phase 2
- Intervention
- Cisplatin
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Sponsor
- ECOG-ACRIN Cancer Research Group
- Enrollment
- 189
- Locations
- 1249
- Primary Endpoint
- Disease-free survival in patients with stage III-IV disease and disruptive p53 mutation
- Status
- Recruiting
- Last Updated
- last month
Overview
Brief Summary
This phase II trial studies how well radiation therapy with or without cisplatin works in treating patients with stage III-IVA 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 Description
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 treatment, patients are followed up every 6 months for 3 years and then every 12 months for 7 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •PRE-REGISTRATION (STEP 0)
- •Pathologically proven diagnosis of squamous cell carcinoma (including variants such as verrucous carcinoma, spindle cell carcinoma, carcinoma not otherwise specified \[NOS\]) of the head/neck (oral cavity, oropharynx, hypopharynx or larynx); pathologic stage III or IVA (American Joint Committee on Cancer \[AJCC\] 8): T3-T4a, N0-3, M0 or T1-T2, N1-3, M0
- •Patient has undergone total resection of the primary tumor with curative intent
- •NOTE: Patient is to be pre-registered to screening (Step 0) and tissue submitted to Foundation Medicine as soon as possible after surgery in order to meet the 8 week deadline to register the patient to Step 1 after surgery; full assay minimum turn-around time is 17-24 days
- •For oropharynx primary tumors, the patient must have negative human papillomavirus (HPV) status of the tumor as determined by p16 protein expression using immunohistochemistry (IHC)
- •Patients with, per the operative and/or pathology report, positive margin(s) (tumor present at the cut or inked edge of the tumor) which is not superceded by an additional margin of tumor-negative tissue, nodal extracapsular extension, and/or gross residual disease after surgery are not eligible
- •A paraffin-embedded surgical tumor tissue specimen has been located is available for shipment to Foundation Medicine, Inc. following pre-registration
- •NOTE: Complete the EA3132-specific FoundationOne requisition form
- •Patients with a history of a curatively treated malignancy must be disease-free for at least two years except for carcinoma in situ of cervix and/or non-melanomatous skin cancer; patients must not have received chemotherapy or investigational therapy within two years of surgical resection of the primary tumor
- •Patient must not have had previous irradiation to the head and neck that would result in overlap in radiation fields for the current disease
Exclusion Criteria
- Not provided
Arms & Interventions
Arm B (IMRT, cisplatin)
Patients undergo IMRT QD 5 days a week and receive cisplatin IV over 1-2 hours weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Cisplatin
Arm A (IMRT)
Patients undergo IMRT QD 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Intensity-Modulated Radiation Therapy
Arm A (IMRT)
Patients undergo IMRT QD 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Arm B (IMRT, cisplatin)
Patients undergo IMRT QD 5 days a week and receive cisplatin IV over 1-2 hours weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Intensity-Modulated Radiation Therapy
Arm B (IMRT, cisplatin)
Patients undergo IMRT QD 5 days a week and receive cisplatin IV over 1-2 hours weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Outcomes
Primary Outcomes
Disease-free survival in patients with stage III-IV disease and 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.
Secondary Outcomes
- Disease-free survival in patients with stage III-IV disease and non-disruptive p53 mutation(Date of randomization to the date of recurrence, second primary tumor from the head and neck region, or death, assessed up to 10 years)
- p53 as a predictive marker of recurrence(Baseline)
- Disease-free survival in patients with stage III-IV disease and wild type p53 mutation(Date of randomization to the date of recurrence, second primary tumor from the head and neck region, or death, assessed up to 10 years)
- Incidence of adverse events graded using Common Terminology Criteria for Adverse Events version 4(Up to 6 weeks)