Induction Chemotherapy With ACF Followed by Chemoradiation Therapy for Adv. Head & Neck Cancer

• Comparison of CR at primary tumor site after ACF to historical CR after ACCF [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  A one-sample test for noninferiority will be used.
• PR at primary tumor site and CR or PR at regional nodes after two cycles of ACF [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  Response will be assessed by laryngoscopy.
• Anatomic tumor response by CT scan after two cycles of ACF [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  Response assessed using RECIST criteria version 1.0
• Metabolic tumor response by FDG-PET/CT after two cycles of ACF [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  Response assessed using RECIST criteria version 1.0
• Survival (OS, DFS and PFS) as a measure of response to ACF in patient population [ Time Frame: 10 years ] [ Designated as safety issue: No ]
  Kaplan-Meier models will be used to estimate median (if the median is reached) and to estimate 1 and 2 year rates with 95% confidence intervals.
• Document and grade adverse events (AE's) with ACF [ Time Frame: 5 months (during ACF and definitive therapy to 30 days after end of treatment) ] [ Designated as safety issue: Yes ]
  Type and grade of toxicity assessed by NCI-CTCAE version 3; Compare AE rates with ACF to those with ACCF (historical data).
• Changes in SPARC and Ki-67 expression [ Time Frame: 2 days (at baseline and Week 6) ] [ Designated as safety issue: No ]
  Primary tumor biopsy; analyzed using IHC.
• Quality of life [ Time Frame: 16 months ] [ Designated as safety issue: No ]
  Assessed using questionnaires administered at 6 time points starting at baseline.

This phase II trial studies the safety and effectiveness of an induction chemotherapy (ACF) consisting of paclitaxel albumin-stabilized nanoparticle formulation (nab-paclitaxel), cisplatin and fluorouracil followed by chemoradiation therapy in treating patients with stage III-IV squamous cell cancer of the head and neck. ACF may be an effective way to reduce or downgrade locally aggressive tumors, and improve the chance of eradication by chemoradiation.

• Drug: paclitaxel albumin-stabilized nanoparticle formulation
  Patients receive ACF induction therapy comprising 2 cycles of nab-paclitaxel IV on days 1, 8, and 15; cisplatin IV on day 1, and fluorouracil IV on days 1-3 of a 21 day cycle. Patients achieving CR/PR receive a third cycle of ACF. All patients then receive definitive radiation therapy with concomitant chemotherapy within 35 days of completing ACF. Definitive therapy consists of IMRT QD 5 times a week for 7 or 8 weeks with cisplatin IV on days 1, 22 and 43 with cetuximab IV once per week.
  Other Name: ABI-007, Abraxane, Albumin-Stabilized Nanoparticle Paclitaxel, nab paclitaxel, nab-paclitaxel, nanoparticle albumin-bound paclitaxel
• Drug: nab-paclitaxel
  nab-paclitaxel 100mg/m2 IV on days 1, 8, and 15 of a 21 day cycle, X 2 cycles. If patients achieve a CR/PR after 2 cycles they may receive a third cycle of ACF.
  Other Names:

  • ABI-007
  • Abraxane
  • Albumin-Stabilized Nanoparticle Paclitaxel
  • nab paclitaxel
  • nab-paclitaxel, nanoparticle
• Drug: Cisplatin
  Cisplatin 75mg/m2 IV on day 1 of a 21 day cycle, X 2 cycles
  Other Names:

  • CACP
  • CDDP
  • CPDD
  • DDP
  • Neoplatin
• Drug: Fluorouracil
  Fluorouracil 750mg/m2 IV on days 1-3 of a 21 day cycle, X 2 cycles
  Other Name: 5-fluorouracil, 5-Fluracil, 5-FU, Adrucil, Efudex, FU
• Radiation: Chemoradiation

  Definitive radiation therapy with concomitant chemotherapy within 35 days of completing ACF.

  RT IMRT QD 5 times a week over 7 wks at 200 cGy fractions for a total dose of 7000 cGy with concomitant chemotherapy, Cisplatin 10mg/m2 Day 1, 22 and 43.

  Other Name: IMRT
• Radiation: Chemoradiation

  Definitive radiation therapy with concomitant chemotherapy within 35 days of completing ACF.

  RT IMRT QD 5 times a week over 7 wks at 200 cGy fractions for a total dose of 7000 cGy with concomitant chemotherapy, Cetuximab (for patients who cannot receive cisplatin) will be started 7 days (+/- 3 days) before starting RT IMRT. The initial (loading) dose of cetuximab 400 mg/m2 IVPB. Subsequently, cetuximab doses of 250 mg/m2 IVPB weekly.

  Other Name: IMRT
• Procedure: Quality-of-life assessment
  ACF baseline, IMRT baseline, Day 7, Week 12, months 6 and 12
  Other Names:

  • FACT H&N
  • FACT/GOG-NTX-4

Inclusion Criteria:

• Patient must have selected stage III or IVa/b head and neck squamous cell carcinoma (HNSCC); all patients must have 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
• Patient must have disease at the oropharynx, hypopharynx, larynx, or oral cavity sub-sites
• Patient must have 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
• Patient myst be >= 18 years of age.
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Absolute neutrophil count (ANC) >= 1500/mcL
• Platelets > 100,000/mcL
• Hemoglobin > 9.0 g/dL
• Total bilirubin =< 1.5 mg/dL
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
• Alkaline phosphatase =< 2.5 x ULN
• Serum creatinine < 1.8 mg/dL
• 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
• Patient must be able to understand and willing to sign an Institutional Review Board (IRB)-approved written informed consent document
• Patient with uncontrolled diabetes or fasting blood glucose level of greater than 200 mg/dL will not be evaluable for PET imaging

Exclusion Criteria:

• Patient must not have had prior chemotherapy, prior epidermal growth factor receptor (EGFR) targeted therapy, or prior radiation therapy for HNSCC
• Patient must not have disease at the nasopharyngeal, sinus, or other sub-site not specified in the inclusion criteria; patient must not have unknown primary squamous cell carcinoma of the head and neck
• Patient must not have a history of prior invasive malignancy diagnosed within 3 years prior to study enrollment other than local stage non-melanoma skin cancer
• Patient must not be receiving any other investigational agents
• Patient must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to any of the agents used in this study
• Patient must not be taking cimetidine or allopurinol; if currently taking either of these medications, patient must discontinue for one week before receiving treatment with nab-paclitaxel
• Patient must not have an 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
• Patient must not be pregnant and/or breastfeeding; a negative serum or urine pregnancy test is required at screening for all female patients of childbearing potential
• Patient must not be known to be human immunodeficiency virus (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
• Patient must not have peripheral neuropathy > grade 1