Nab-Paclitaxel and Cisplatin or Nab-paclitaxel as Induction Therapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (HNSCC)
Condition: Squamous Cell Carcinoma of the Head and Neck; Carcinoma, Squamous Cell of the Head and Neck; Cancer of Head and Neck; Cancer of the Head and Neck; Head and Neck Cancer; Neoplasms, Head and Neck
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck
Intervention: nab-Paclitaxel; Cisplatin; Cetuximab; Intensity-Modulated Radiation Therapy
Intervention MeSH terms: Paclitaxel; Cisplatin; Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 96.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      In this trial, the objectives are to determine the efficacy and toxicity of induction
      chemotherapy (IC) with nab-paclitaxel + cisplatin (Arm 1: AP) and with nab-paclitaxel (Arm 2:
      A) alone in patients with HNSCC, and to compare these data to nab-paclitaxel, cisplatin, and
      5-FU (APF). The investigators also hypothesize that the high anti-tumor efficacy of
      nab-paclitaxel in HNSCC is due to the upregulation of macropinocytosis, a result of the
      frequent presence of Ras and PI3K (and epidermal growth factor receptor -EGFR) activation in
      this cancer.

      Amendment to Add Arm 3:

      In this amendment, the investigators retain the AP + concurrent chemoradiation therapy (CRT)
      backbone but de-escalate the dose of radiation therapy (RT) from 70 Gy to 42 Gy. The
      investigators also plan to administer one dose (vs three) of cisplatin during RT. This novel
      treatment approach will be evaluated in patients with HPV-related oropharyngeal squamous cell
      carcinoma (OPSCC) (Arm 3), a sub-group with a very favorable prognosis.
    

Eligibility criteria:

        Inclusion Criteria: Arms 1 and 3 - AP

          -  Diagnosis of selected Stage III or IVa/b HNSCC. Arm 1: T2-T4 primary tumors. Arm 3:
             T2T1-T4 primary tumors. Although most of these patients will have regional nodal
             disease, patients with no nodal disease will also be eligible.

          -  Arm 1: Presence of disease at the oropharynx, hypopharynx, or larynx sub-sites.

          -  Arm 3: Presence of disease at the oropharynx sub-sites, which is HPV-related as
             verified by p16, a surrogate marker of HPV, or HPV ISH or PCR.

          -  Presence of measurable disease defined as lesions that can be accurately measured in
             at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan.

          -  At least 18 years of age.

          -  Women of childbearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control, abstinence) prior to study entry, for
             the duration of study participation, and for 3 months after completing treatment.
             Should a woman become pregnant or suspect she is pregnant while participating in this
             study, she must inform her treating physician immediately.

          -  Able to understand and willing to sign an IRB-approved written informed consent
             document.

          -  ECOG performance status ≤ 1.

          -  Adequate bone marrow and organ function as defined below:

               -  ANC: ≥ 1500/mcL.

               -  Platelets: > 100,000/mcL.

               -  Hemoglobin > 9.0 g/dL

               -  Total bilirubin ≤ 1.5 mg/dL

               -  AST/ALT/alkaline phosphatase: ≤ 2.5 x ULN.

               -  Serum creatinine: < 1.5 mg/dL or calculated GFR ≥ 75 cc/min. CrCl by Cockcroft
                  Gault will be used to estimate GFR.

               -  Pulmonary: no requirement for supplemental oxygen and no evidence of
                  moderate-severe chronic obstructive pulmonary disease (COPD) by pulmonary
                  function tests (PFTs).

        Inclusion Criteria: Arm 2 - A

          -  Diagnosis of selected Stage III or IVa/b HNSCC. T2-T4 primary tumors. (Patients with
             T1 tumors will be excluded). Although most of these patients will have regional nodal
             disease, patients with no nodal disease will also be eligible.

          -  Presence of disease at the oropharynx, hypopharynx, or larynx sub-sites.

          -  Presence of measurable disease defined as lesions that can be accurately measured in
             at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan.

          -  At least 18 years of age.

          -  Women of childbearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control, abstinence) prior to study entry, for
             the duration of study participation, and for 3 months after completing treatment.
             Should a woman become pregnant or suspect she is pregnant while participating in this
             study, she must inform her treating physician immediately.

          -  Able to understand and willing to sign an IRB-approved written informed consent
             document.

          -  ECOG performance status < 3.

          -  Adequate bone marrow and organ function as defined below:

               -  ANC: ≥ 1500/mcL.

               -  Platelets: ≥ 100,000/mcL.

               -  Hemoglobin > 9.0 g/dL

               -  Total bilirubin ≤ 2.0 mg/dL

               -  AST/ALT/alkaline phosphatase: ≤ 5x ULN.

               -  Calculated GFR >30 cc/min. CrCl by Cockcroft Gault will be used to estimate GFR.

               -  Pulmonary: patients with a requirement for supplemental oxygen or evidence of
                  moderate-severe COPD by PFTs are permitted to enroll.

          -  If a patient fully meets criteria for Arm 1, but has profound hearing loss and the
             physician feels that the patient should not receive Cisplatin, the patient will be
             eligible for Arm 2.

          -  If a patient fully meets criteria for Arm 1, but has a history of solid organ or bone
             marrow transplant, the patient will be eligible for Arm 2 (due to contraindications of
             Cisplatin with medications the patient is taking due to the transplant).

        Exclusion Criteria (Arm 1 and Arm 2)

          -  Prior chemotherapy, prior EGFR targeted therapy, or prior radiation therapy for HNSCC.

          -  Disease at the nasopharyngeal, sinus, oral cavity, or other sub-site not specified as
             eligible.

          -  Diagnosis of unknown primary squamous cell carcinoma of the head and neck.

          -  History of prior invasive malignancy diagnosed within 3 years prior to study
             enrollment; exceptions are malignancies with a negligible risk of metastasis or death
             (e.g., expected 5-year OS > 90%) that were treated with an expected curative outcome,
             such as squamous cell carcinoma of the skin, in-situ carcinoma of the cervix uteri,
             non-melanomatous skin cancer, carcinoma in situ of the breast, or incidental
             histological finding of prostate cancer (TNM stage of T1a or T1b)

          -  Receiving any other investigational agents.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to any of the agents used in this study.

          -  Taking cimetidine or allopurinol. If currently taking either of these medications,
             patient must discontinue for one week before receiving treatment with nab-paclitaxel.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             serious infection, symptomatic congestive heart failure, unstable angina pectoris,
             cardiac arrhythmia, or serious psychiatric illness/social situations that would limit
             compliance with study requirements.

          -  Pregnant and/or breastfeeding. A negative serum or urine pregnancy test is required at
             screening for all female patients of childbearing potential.

          -  Known to be HIV-positive on combination antiretroviral therapy because of the
             potential for pharmacokinetic interactions with the study agents. In addition, these
             patients are at increased risk of lethal infections when treated with marrow
             suppressive therapy. Appropriate studies will be undertaken in patients receiving
             combination antiretroviral therapy when indicated.

          -  Peripheral neuropathy > grade 1.