The Quarterback Trial: Reduced Dose Radiotherapy for HPV+ Oropharynx Cancer
Condition: Squamous Cell Carcinomas
MeSH terms: Oropharyngeal Neoplasms
Intervention: Reduced Dose Radiation; Standard Dose Radiation; Carboplatin
Intervention description: Reduced Dose Radiation (5600 cGy) dose radiotherapy; Standard Dose Radiation (7000 cGy) dose radiotherapy; Day 1, every 7 days ( + 2 days)
Intervention MeSH terms: Carboplatin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Reduced radiotherapy; Randomization, Phase III; Reduced radiation therapy; head and neck; oropharynx; unknown primary (cervical lymph nodes); nasopharynx primary; HPV; p16

Summary:

      This trial aims to directly compare a reduced radiation dose to the standard of care in
      HPVOPC for non-inferiority, thus allowing for direct comparison of outcomes between the two
      groups. The study hypothesis is that LRC and PFS at 3 years for reduced dose CRT are
      non-inferior to standard dose CRT.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants must have histologically or cytologically confirmed squamous cell
             carcinoma of the oropharynx, unknown primary, or nasopharynx that is HPV positive as
             determined by PCR and p16 positive as determined by IHC. Tissue from the primary site
             must be available for biomarker studies. PCR and IHC must be performed in the central
             laboratory (Zhang, MSSM)

          -  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 in
             the protocol.

          -  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 maybe treated on study with bilirubins > the ULN for the institution if
             other liver function 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.

          -  Other serious illnesses or medical conditions including but not limited to:

               1. Unstable cardiac disease despite treatment, myocardial infarction within 6 months
                  prior to study entry

               2. History of significant neurologic or psychiatric disorders including dementia or
                  seizures

               3. Active clinically significant uncontrolled infection

               4. Active peptic ulcer disease defined as unhealed or clinically active

               5. Hypercalcemia

               6. Active drug addiction including alcohol, cocaine or intravenous drug use defined
                  as occurring within the 6 months preceding diagnosis

               7. 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

               8. Autoimmune disease requiring therapy, prior organ transplant, or HIV infection

               9. Interstitial lung disease

              10. Hepatitis C (test required)

          -  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 within the past 20 years with a cumulative Pack Year history of > 20
             Pack Years or active smoking (Defined as > 1 cigarette per day) within the last 2
             years