Clinical trial NCT01412229: Induction Chemotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Head and Neck Cancer
Keywords: Head and neck cancer
Phase II
Locally advanced
Squamous Cell
Carboplatin
Nab-paclitaxel
Abraxane
Cetuximab
Induction
Chemotherapy
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
First posted: 2011-08-09
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Clinical Response Rate Following Induction Chemotherapy
timeFrame: 9 weeks
Secondary outcomes:
measure: Rate of Complete Response Following Induction Chemotherapy
timeFrame: Baseline evaluation to 3 weeks after induction chemotherapy
measure: Progression Free Survival
timeFrame: 1 year
measure: Objective Response Rate (CR+PR)
timeFrame: 20 weeks
measure: Complete Response Rate (CR)
timeFrame: 20 weeks
measure: Overall Survival
timeFrame: 1 year
measure: Number of Participants With at Least One Grade 3-4 Toxicity
timeFrame: 9 Weeks
measure: Number of Participants With at Least One Grade 3-4 Toxicity, Listed by Event
timeFrame: 24 Weeks
measure: Patient-reported Quality of Life Scores
timeFrame: screening until one year after treatment
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Jared Weiss, MD
role: PRINCIPAL_INVESTIGATOR
References: