Induction Chemotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Study Overview
=================
Brief Summary
-----------------
This is a non-randomized, open-label phase II trial of 40 patients with poor prognosis head and neck cancer, defined as surgically unresectable and/or ≥N2b disease and judged appropriate for non-surgical definitive therapy.

Detailed Description
-----------------
This is a non-randomized, open-label phase II trial of 40 patients with poor prognosis head and neck cancer, defined as surgically unresectable and/or ≥N2b disease and judged appropriate for non-surgical definitive therapy. Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 with good organ function and will be treated with six weekly cycles of carboplatin, nab-paclitaxel and cetuximab prior to scheduled concomitant chemoradiation. The study is designed to evaluate whether this induction regimen can result in an improved response rate (complete response (CR) + partial response (PR)) with less toxicity than the current standard induction docetaxel, cisplatin and 5-fluorouracil (TPF) regimen.

Official Title
-----------------
A Phase II Study of Carboplatin, Nab-paclitaxel and Cetuximab for Induction Chemotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Conditions
-----------------
Head and Neck Cancer

Intervention / Treatment
-----------------
* Drug: Cetuximab
* Drug: Nab-paclitaxel
* Drug: Carboplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed SCCHN or poorly differentiated or undifferentiated cancer of the head and neck. Measurable disease. All primary sites are eligible excluding nasopharyngeal. Surgically unresectable and/or N2b or greater nodal disease; Note: surgical unresectability will be defined as the combination of the treating surgeon's judgment of unresectability plus one of the following objective criteria: Encasement of tumor or nodes to the carotid artery or ¾ encasement of the carotid artery. Involvement of prevertebral musculature Invasion of the bone of the skull base Need for glossectomy or extensive glossal resection where functional outcome is considered unacceptable to surgeon or patient Involvement of the cervical spine Severe, unacceptable functional deficit that would result from any proposed definitive surgical resection. ECOG performance status 0-1 Prior therapy: Chemotherapy: No prior chemotherapy for the treatment of SCCHN. Platinum chemotherapy: No previous history of carboplatin or cisplatin therapy. Nab-paclitaxel: No previous treatment with nab-paclitaxel or another taxane. Cetuximab: No previous treatment with cetuximab Or another epidermal growth factor receptor (EGFR) inhibitor. Radiation therapy: No prior radiation to the head and neck region. Age > or = 18 years. Men and women are eligible for participation. Must have acceptable organ and marrow function as defined below. Laboratory tests should be completed within 14 days prior to registration: Absolute Neutrophil Count (ANC) > or = 1,500/mm3 Platelets > or = 100,000/mm3 Hemoglobin (Hgb) > 9g/dL Total bilirubin < or = 1.5mg/dL Albumin > 2.5 g/dL Aspartate aminotransferase (AST)/Alanine Aminotransferase (ALT) < or = 2.5 times institutional upper limit of normal, alkaline phosphatase < 2.5 x upper limit of normal, glomerular filtration rate (GFR) > 30 mL/min (by standard Cockcroft and Gault formula or measured via 24 hour urine collection) No pre-existing neuropathy greater than grade I Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to day 1 of study treatment. Women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation and for three months after completing treatment. Adequate contraception is defined as any medically recommended method (or combination of methods) as per standard of care. Patients must have the ability to understand and the willingness to sign a written informed consent document. Patients must have a negative result for preformed immunoglobulin E (IgE) antibodies to galactose-alpha-1,3,-galactose. Exclusion Criteria: Prior treatment with any of the study medications. Prior radiation to any of the field required to treat the tumor. Any metastatic disease. The patient may have had a prior malignancy but must be disease-free for three years prior to study entry. A history of superficial non-melanoma skin cancer or in situ carcinoma of the cervix less than three years will be allowed. Pregnant or lactating female Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics, or psychiatric illness/social situations that would limit compliance with study requirements. Cardiac disease such as symptomatic congestive heart failure, unstable angina pectoris, or myocardial infarction will result in exclusion only if active within the past six months. Cardiac dysrhythmia will only result in exclusion if active and symptomatic (for example, rate-controlled atrial fibrillation will not result in exclusion).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>nab-paclitaxel 100mg/m2 Carboplatin area under curve (AUC)2 (IV) Cetuximab 400mg/m2 week 1 then 250mg/m2 for six weeks | Drug: Cetuximab<br>* Weekly cetuximab given intravenously for 6 weeks during induction chemotherapy and continue during the 2-3 week break prior to definitive chemoradiotherapy.<br>* Other names: Erbitux;Drug: Nab-paclitaxel<br>* Weekly nab-paclitaxel given intravenously following cetuximab infusion for 6 weeks.<br>* Other names: Abraxane;Drug: Carboplatin<br>* Weekly carboplatin given intravenously following nab-paclitaxel infusion for 6 weeks.<br>* Other names: Paraplatin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response Rate Following Induction Chemotherapy | Evaluation of target lesions via imaging with CT or MRI scans at 2-3 weeks post induction chemotherapy. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions. | 9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Complete Response Following Induction Chemotherapy | Report the rate of complete responses, defined as disappearance of all target lesions, following induction chemotherapy. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions. | Baseline evaluation to 3 weeks after induction chemotherapy | 
| Progression Free Survival | Rate of Progression Free Survival (Time to death or progression defined by imaging of target lesions via CT or MRI scan post induction chemotherapy and chemoradiotherapy every 3 months for one year) | 1 year | 
| Objective Response Rate (CR+PR) | Objective Response Rate as defined by RECIST 1.1 after induction chemotherapy followed by definitive chemoradiation. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR. | 20 weeks | 
| Complete Response Rate (CR) | Complete Response Rate as defined by RECIST 1.1 after induction chemotherapy followed by definitive chemoradiation | 20 weeks | 
| Overall Survival | Rate of Overall Survival | 1 year | 
| Number of Participants With at Least One Grade 3-4 Toxicity | Toxicity will be assessed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4. | 9 Weeks | 
| Number of Participants With at Least One Grade 3-4 Toxicity, Listed by Event | Toxicity will be assessed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4. | 24 Weeks | 
| Patient-reported Quality of Life Scores | Functional Assessment of Cancer Therapy - Head & Neck (FACT-HN) is the FACT-G and a 12 item head and neck cancer specific subscale completed at screening (Screening), 3 weeks post induction chemotherapy (Treatment Break), 7 weeks post concomitant chemoradiotherapy (7 weeks Off Treatment), one year post off-treatment (1 year Off Treatment). The FACT-G is a 27 item measure of general QOL assessing function in 4 domains: physical well-being (PWB), social-family well-being (SFWB), emotional well-being (EWB) and functional well-being (FWB). Items are rated by patients on a Likert scale from 0 to 4 (resulting in potential total scores between 0 and 156). Higher scores represent better QOL. | screening until one year after treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Head and neck cancer, Phase II, Locally advanced, Squamous Cell, Carboplatin, Nab-paclitaxel, Abraxane, Cetuximab, Induction, Chemotherapy