Clinical Trials /

Quarterback 2b - Sequential Therapy With Reduced Dose Chemoradiotherapy for HPV Oropharynx Cancer

NCT02945631

Description:

The purpose of this study is to establish the efficacy and toxicity of low dose chemoradiotherapy after induction chemotherapy in patients with locally advanced HPV+ oropharynx cancer and establish prognostic factors that would apply to help select patients for this treatment in the future.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma of Unknown Primary
  • Hypopharyngeal Squamous Cell Carcinoma
  • Nasal Cavity Squamous Cell Carcinoma
  • Nasopharyngeal Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
  • Supraglottic Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Quarterback 2b - Sequential Therapy With Reduced Dose Chemoradiotherapy for HPV Oropharynx Cancer
  • Official Title: Quarterback 22: A Phase II Clinical Trial of Sequential Therapy and De-Intensified Chemoradiotherapy for Locally Advanced HPV Positive Oropharynx Cancer

Clinical Trial IDs

  • ORG STUDY ID: GCO 16-0609
  • NCT ID: NCT02945631

Conditions

  • Locally Advanced HPV Positive Oropharynx Cancer

Purpose

The purpose of this study is to establish the efficacy and toxicity of low dose chemoradiotherapy after induction chemotherapy in patients with locally advanced HPV+ oropharynx cancer and establish prognostic factors that would apply to help select patients for this treatment in the future.

Detailed Description

      In general, patients with Human Papilloma Virus Oropharynx Cancer (HPVOPC) are young and will
      live for prolonged periods. They are at high risk for long-term toxicity and mortality from
      radiotherapy. While the long-term consequences of chemotherapy for head and neck cancer are
      relatively constrained, high-dose radiotherapy (RT) and chemoradiotherapy (CRT) substantially
      impact on local tissues and organ function and result in a significant rate of late mortality
      and morbidity in patients. Studies are now being designed to reduce the impact of RT and CRT
      for patients. Identifying appropriate endpoints and study arms which will allow an early
      assessment of outcomes will be problematic, particularly for equivalence studies wherein
      survival differences are small, and where prolonged time periods and large patient numbers
      are necessary to accurately assess outcomes. For Sequential Therapy as given with TAX 324,
      3-year PFS may be an appropriate endpoint. The same may not be possible for CRT. The best
      example of changing outcomes in CRT trials would be R91-11, in which a premature negative
      conclusion regarding the efficacy of induction therapy was published with the early analysis.
      Late toxicity and morbidity, a hallmark of upfront cisplatin-based CRT trials, led to
      equivalence between induction therapy and CRT for laryngectomy-free survival at 5 years, and
      more importantly a non-significant relative 10% improvement in overall survival in the PF
      induction arm compared to the CRT arm which included an every 3-week bolus cisplatin for 3
      cycles during radiotherapy.

      The survival results in HPVOPC achieved in TAX 324 and preliminary data from ECOG 1308
      strongly suggest that it might be possible to reduce long-term morbidity in HPVOPC and
      preserve survival perhaps by better patient selection and by reducing radiotherapy intensity
      in the context of ST for more advanced cases. Best approach of HPV-negative disease might be
      with novel therapies and more aggressive Sequential Therapy (ST) or CRT.

      Current radiation dose reduction trials are under way in ECOG, RTOG and other radiation based
      groups. The data from TAX 324 suggest that it is possible to reduce the radiation dose
      because of the superior progression free survival and the ability to select risk based CRT.
    

Trial Arms

NameTypeDescriptionInterventions
Reduced Dose RadiationExperimentalAll patients will receive daily radiation treatment with intensity-modulated radiotherapy (IMRT) - PTV56 and PTV50.4. Treatment will be given 5 days per week and will not routinely be delivered on Saturday, Sunday or major holidays unless a treatment is missed during the week due to technical and/or medical reasons. No more than 5 treatments should be given per week.

    Eligibility Criteria

            Inclusion Criteria:
    
            Participants must meet the following criteria to be eligible to participate in the study.
            Patients may enroll in the study if they meet all of the entry criteria, were candidates
            for induction chemotherapy regardless of HPV status and have to start therapy for logistic
            reasons prior to p16 and HPV testing. They will enter the experimental post-Induction
            portion of the study if the surgical specimens or biopsies are proven to be HPV+ on PCR
            testing. Patients who are HPV negative will be taken off study and treated with SOC
            radiotherapy and surgery:
    
              -  Participants must have histologically or cytologically confirmed squamous cell
                 carcinoma of the oropharynx, hypopharynx, supraglottic larynx, nasal cavity, unknown
                 primary, or nasopharynx that is p16 and HPV positive. Tissue from the primary site or
                 lymph node must be available for biomarker studies and for PCR testing. IHC must be
                 performed in a lab verified by the central laboratory or the slides must be available
                 for review by the central laboratory and PCR must be done in the central laboratory
                 prior to radiotherapy. HPVPCR must be performed and results available for reduced dose
                 therapy after induction.
    
              -  Patients who are on the Quarterback Trial when Quarterback 2 is activated and who have
                 been randomized to radiotherapy arm will be asked to transfer to this trial and
                 receive the Quarterback 2 defined radiotherapy.
    
              -  Stage 3 or 4 disease without evidence of distant metastases.
    
              -  At least one clinically evaluable or uni- or bi-dimensionally measurable lesion by
                 RECIST 1.1 criteria.
    
              -  Age ≥ 18 years.
    
              -  No previous surgery, radiation therapy or chemotherapy for SSCHN (other than biopsy or
                 tonsillectomy) is allowed at time of study entry.
    
              -  ECOG performance status of 0 or 1.
    
              -  No active alcohol addiction (as assessed by medical caregiver and defined as at least
                 6 months without activity).
    
              -  Participants must have adequate bone marrow, hepatic and renal functions as defined
                 below:
    
              -  - Hematology:
    
              -  - Neutrophil count ≥ 1.5 x 10^9/l.
    
              -  - Platelet count ≥ 100 x 10^9/l.
    
              -  - Hemoglobin ≥ 10g/dl.
    
              -  - Renal function ≥ 60 ml/min (actual or calculated by the Cockcroft-Gault method) as
                 follows: CrCl (ml/min) = (140-age)(weight kg)/(mL/min) / 72 x serum creatinine (mg/dL)
    
              -  - N.B. For females, use 85% of calculated CrCl value. Or a Creatinine ≤ the upper
                 limits of normal
    
              -  - Hepatic:
    
              -  - Total Bilirubin ≤ institutional upper level of normal (ULN)
    
              -  - AST or ALT and Alkaline Phosphatase must be within the range allowing for
                 eligibility
    
              -  Women of childbearing potential must have a negative pregnancy test within 7 days of
                 starting treatment.
    
              -  Ability to understand and the willingness to sign a written informed consent document.
    
              -  Patients with Gilbert's Disease and absent hepatic pathology by history and clinical
                 assessment may be treated on study with bilirubin > the ULN for the institution if
                 other liver functions studies are within the normal range
    
            Exclusion Criteria:
    
              -  Pregnant or breast feeding women, or women and men of childbearing potential not
                 willing to use adequate contraception while on treatment and for at least 3 months
                 thereafter.
    
              -  Previous or current malignancies at other sites, with the exception of adequately
                 treated in situ carcinoma of the cervix, basal or squamous cell carcinoma of the skin,
                 thyroid cancer, or other cancer curatively treated by surgery and with no current
                 evidence of disease for at least 5 years.
    
              -  Symptomatic peripheral neuropathy grade > 2 by NCI Common Terminology Criteria
                 (NCI-CTC) version 4.
    
              -  Symptomatic altered hearing > grade 2 by NCI-CTCv4 criteria.These patients can be
                 entered by substituting carboplatin for cisplatin with an AUC of 6.0
    
              -  Other serious illnesses or medical conditions including but not limited to:
    
              -  - Unstable cardiac disease despite treatment, myocardial infarction within 6 months
                 prior to study entry
    
              -  - History of significant neurologic or psychiatric disorders including dementia or
                 seizures
    
              -  - Active clinically significant uncontrolled infection
    
              -  - Active peptic ulcer disease defined as unhealed or clinically active
    
              -  - Hypercalcemia
    
              -  - Active drug addiction including alcohol, cocaine or intravenous drug use defined as
                 occurring within the 6 months preceding diagnosis
    
              -  - Chronic Obstructive Pulmonary Disease, defined as being associated with a
                 hospitalization for pneumonia or respiratory decompensation within 12 months of
                 diagnosis. This does not include obstruction from tumor
    
              -  - Autoimmune disease requiring therapy, prior organ transplant, or HIV infection
    
              -  - Interstitial lung disease
    
              -  - Hepatitis C by history, and confirmed by serology
    
              -  Patients that have experienced an involuntary weight loss of more than 25% of their
                 body weight in the 2 months preceding study entry.
    
              -  Concurrent treatment with any other anticancer therapy.
    
              -  Participation in an investigational therapeutic drug trial within 30 days of study
                 entry.
    
              -  Active smoking or a cumulative pack year history of > 20 pack years, active smoking is
                 (Defined as ≥ 1 cigarette per day) within the last 5 years.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Progression Free Survival (PFS)
    Time Frame:3 years
    Safety Issue:
    Description:The comparative rate of progression free survival

    Secondary Outcome Measures

    Measure:Local-regional control (LRC)
    Time Frame:3 years
    Safety Issue:
    Description:The comparative rate of local-regional control
    Measure:Local-regional control (LRC)
    Time Frame:5 years
    Safety Issue:
    Description:The comparative rate of local-regional control
    Measure:Overall Survival (OS)
    Time Frame:3 years
    Safety Issue:
    Description:
    Measure:Overall Survival (OS)
    Time Frame:5 years
    Safety Issue:
    Description:
    Measure:Acute Toxicity
    Time Frame:5 years
    Safety Issue:
    Description:Rate of acute toxicity
    Measure:Long Term Toxicity
    Time Frame:5 years
    Safety Issue:
    Description:Rate of long term toxicity

    Details

    Phase:N/A
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Icahn School of Medicine at Mount Sinai

    Trial Keywords

    • HPV
    • Induction Chemotherapy
    • De-Intensified Chemoradiotherapy
    • Oropharynx Cancer

    Last Updated

    October 24, 2019