Nab-paclitaxel and Carboplatin Followed by Response-Based Local Therapy in Treating Patients With Stage III or IV HPV-Related Oropharyngeal Cancer
Condition: Human Papilloma Virus Infection; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Oropharynx
MeSH terms: Papillomavirus Infections; Carcinoma; Carcinoma, Squamous Cell; Oropharyngeal Neoplasms; Papilloma
Intervention: paclitaxel albumin-stabilized nanoparticle formulation; carboplatin; radiation therapy; paclitaxel; fluorouracil; hydroxyurea; cisplatin; laboratory biomarker analysis; quality-of-life assessment
Intervention description: Given IV; Given IV; Undergo radiation therapy; Given IV; Given IV; Given PO; Given IV; Correlative studies; Ancillary studies
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel; Carboplatin; Fluorouracil; Hydroxyurea
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 62.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle
      formulation) and carboplatin followed by response-based local therapy in treating patients
      with stage III or IV human papillomavirus (HPV)-related oropharyngeal cancer. Drugs used in
      chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, carboplatin,
      hydroxyurea, fluorouracil, paclitaxel, and 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 spreading. Radiation therapy uses high energy x rays to kill tumor cells.
      Giving nab-paclitaxel and carboplatin before chemoradiation may make the tumor smaller and
      reduce the amount of chemotherapy and radiation therapy needed. Assigning chemotherapy and
      radiation therapy based on response (response-based therapy) and giving patients who are
      responding well lower doses of treatment may help reduce the occurrence of side effects.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have pathologically confirmed HPV-positive squamous cell carcinoma

          -  HPV testing must follow the following criteria

               -  HPV testing using an E6/E7 based assay is preferred, and does not require any
                  validation (e.g. HPV in situ hybridization [ISH] or HPV E6/E7 polymerase chain
                  reaction [PCR])

               -  For oropharyngeal tumors p16 immunohistochemistry (IHC) positivity is sufficient
                  to enroll and initiate treatment (p16 IHC interpretation to follow guidelines by
                  Jordan/Lingen et al 2012); it is recommended that p16 IHC positivity is validated
                  at a later point (during or after treatment) using an E6/E7 based test at the
                  University of Chicago and provided slides will be used

               -  For non-operative (OP) tumors accurate HPV testing (i.e. ISH, or E6/E7 based
                  testing) is required for enrollment and treatment initiation

          -  Availability of >= 10 unstained 5 micron slides

          -  Patients with American Joint Committee on Cancer (AJCC) (7th edition, 2010) nodal
             stage N2 or N3 or a T4 primary tumor

          -  The primary and nodal involvement must be assessable on clinical exam (mucosal and
             lymph node exam)

          -  The primary and nodal involvement must have been defined bi- or uni-dimensional
             measurements measurable by RECIST

          -  No previous radiation or chemotherapy for a head and neck cancer

          -  No surgical resection for a head and neck cancer within 8 weeks of enrollment
             (although lymph node biopsy including excision of an individual node with presence of
             residual nodal disease, or surgical biopsy of the tumor is acceptable)

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Karnofsky >= 70%)

          -  Leukocytes >= 3000/mm^3

          -  Platelets >= 100,000/mm^3

          -  Absolute neutrophil count >= 1,500

          -  Hemoglobin > 9.0 gm/dL

          -  Albumin > 2.9 gm/dL

          -  Total bilirubin =< 1.5 mg/dl

          -  Creatinine clearance > 45 mL/min (or serum creatinine [SCr] =< 1.5 mg/dL), normal
             within 2 weeks prior to start of treatment

          -  The standard Cockcroft and Gault formula or the measured glomerular filtration rate
             must be used to calculate creatinine clearance (CrCl) for enrollment or dosing

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 X upper
             limit of normal (ULN)

          -  Alkaline phosphatase =< 2.5 X ULN

          -  Patients must sign a study-specific informed consent form prior to study entry;
             patients should have the ability to understand and the willingness to sign a written
             informed consent document

        Exclusion Criteria:

          -  Unequivocal demonstration of distant metastases (M1 disease)

          -  Intercurrent medical illnesses which would impair patient tolerance to therapy or
             limit survival; including but not limited to ongoing or active infection,
             immunodeficiency, symptomatic congestive heart failure, pulmonary dysfunction,
             cardiomyopathy, unstable angina pectoris, cardiac arrhythmia or psychiatric
             illness/social situations that would limit compliance

          -  Pregnant and nursing women are excluded; men and women of child-bearing potential are
             eligible but must consent to using effective contraception during therapy and for at
             least 3 months after completing therapy; women with child-bearing potential must have
             a negative serum or urine beta-human chorionic gonadotropin (B-hCG) pregnancy test at
             screening

          -  Other coexisting malignancies or malignancies diagnosed within the previous 3 years no
             evidence of disease for at least 3 years; exceptions to this include non-melanoma skin
             cancer, cervical cancer in situ, well differentiated thyroid cancer or prostate
             cancer; other cancers that per assessment of the PI are not prognosis limiting can be
             allowed after review by the PI

          -  Prior surgical therapy other than incisional or excisional biopsy and organ-sparing
             procedures such as debulking of airway-compromising tumors or neck dissection in a
             patient with an unknown primary tumor; residual tumor is required for enrollment on
             study

          -  Patients receiving other investigational agents

          -  Peripheral neuropathy >= grade 1