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.
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.
