Clinical Trials /

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

NCT02734537

Description:

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.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Radiation Therapy With or Without Cisplatin in Treating Patients With Stage III-IVA Squamous Cell Carcinoma of the Head and Neck Who Have Undergone Surgery
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: EA3132
  • SECONDARY ID: NCI-2015-01911
  • SECONDARY ID: EA3132
  • SECONDARY ID: EA3132
  • SECONDARY ID: U10CA180820
  • NCT ID: NCT02734537

Conditions

  • Head and Neck Squamous Cell Carcinoma
  • Hypopharyngeal Squamous Cell Carcinoma
  • Laryngeal Squamous Cell Carcinoma
  • Laryngeal Squamous Cell Carcinoma, Spindle Cell Variant
  • Lip and Oral Cavity Squamous Cell Carcinoma
  • p16INK4a Negative Oropharyngeal Squamous Cell Carcinoma
  • Stage III Hypopharyngeal Carcinoma AJCC v8
  • Stage III Laryngeal Cancer AJCC v8
  • Stage III Lip and Oral Cavity Cancer AJCC v8
  • Stage III Oral Cavity Verrucous Carcinoma
  • Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8
  • Stage IVA Hypopharyngeal Carcinoma AJCC v8
  • Stage IVA Laryngeal Cancer AJCC v8
  • Stage IVA Lip and Oral Cavity Cancer AJCC v8
  • Stage IVA Oral Cavity Verrucous Carcinoma
  • Stage IVA Oropharyngeal (p16-Negative) Carcinoma AJCC v8

Interventions

DrugSynonymsArms
CisplatinAbiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, PlatosinArm B (IMRT, cisplatin)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A (IMRT)ExperimentalPatients undergo IMRT QD 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.
    Arm B (IMRT, cisplatin)ExperimentalPatients 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.
    • Cisplatin

    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
    
              -  Patients with recurrent disease or multiple primaries are ineligible
    
              -  RANDOMIZATION (STEP 1)
    
              -  NOTE: Patient must meet all eligibility criteria outlined in pre-registration; patient
                 may not be randomized until site has been notified that the central determination of
                 p53 mutation status of the surgical tumor tissue has been completed and site has been
                 notified of assay completion
    
              -  Per the operative report, the gross total resection of the primary tumor with curative
                 intent was completed within 8 weeks prior to randomization
    
              -  The patient must have the following assessments done =< 8 weeks prior to
                 randomization:
    
                   -  Examination by a head and neck surgeon
    
                   -  Chest x-ray (or chest computed tomography [CT] scan or CT/positron emission
                      tomography [PET] of the chest or magnetic resonance imaging [MRI]) to rule out
                      distant metastatic disease
    
              -  Patient has Eastern Cooperative Oncology Group (ECOG) performance status 0-1 within 2
                 weeks prior to randomization
    
              -  Women must not be pregnant or breast-feeding; females of childbearing potential must
                 have a blood or urine study within 2 weeks prior to randomization to rule out
                 pregnancy; a female of childbearing potential is any woman, regardless of sexual
                 orientation or whether they have undergone tubal ligation, who meets the following
                 criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not
                 been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses
                 at any time in the preceding 24 consecutive months)
    
              -  Women of childbearing potential and sexually active males must be strongly advised to
                 use an accepted and effective method of contraception or to abstain from sexual
                 intercourse for the duration of their participation in the study and until 60 days
                 from the last study treatment
    
              -  Absolute neutrophil count >= 1,500/mm^3 within 4 weeks prior to randomization
    
              -  Platelets >= 100,000/mm^3 within 4 weeks prior to randomization
    
              -  Total bilirubin =< the upper limit of normal (ULN) within 4 weeks prior to
                 randomization
    
              -  Calculated creatinine clearance must be > 60 ml/min using the Cockcroft-Gault formula
                 within 4 weeks prior to randomization
    
              -  Patient must not have an intercurrent illness likely to interfere with protocol
                 therapy
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

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

    Secondary Outcome Measures

    Measure:Disease-free survival in patients with stage III-IV disease and 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
    Safety Issue:
    Description:Kaplan-Meier estimates will be used to estimate event-time distributions and comparison between arms will be performed using a log-rank test.
    Measure:Disease-free survival in patients with stage III-IV disease and 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
    Safety Issue:
    Description:Kaplan-Meier estimates will be used to estimate event-time distributions and comparison between arms will be performed using a log-rank test.
    Measure:Incidence of adverse events graded using Common Terminology Criteria for Adverse Events version 4
    Time Frame:Up to 6 weeks
    Safety Issue:
    Description:Toxicity will be examined by arm and compared using the Fisher's exact test.
    Measure:p53 as a predictive marker of recurrence
    Time Frame:Baseline
    Safety Issue:
    Description:To evaluate whether p53 is a predictive marker, a p53 by treatment arm interaction term will be tested in a Cox proportional hazards model.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:ECOG-ACRIN Cancer Research Group

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