Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Radiation Therapy and Cisplatin or Panitumumab in Treating Patients With Locally Advanced Stage III or Stage IV Head and Neck Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Active 18 and over Other CAN-NCIC-HN6 HN6, NCT00820248

Objectives

Primary

1. To compare the progression-free survival (PFS) of patients with locally advanced squamous cell carcinoma of the head and neck treated with standard fractionation radiotherapy and high-dose cisplatin vs accelerated fractionation radiotherapy and panitumumab.

Secondary

1. To compare overall survival of patients treated with these regimens.
2. To compare local and regional PFS of patients treated with these regimens.
3. To compare distant metastasis in patients treated with these regimens.
4. To compare adverse events, including late radiotherapy-related adverse events in patients treated with these regimens.
5. To compare quality of life (QOL) of patients treated with these regimens.
6. To compare swallowing-related QOL of patients treated with these regimens.
7. To compare economic evaluation (cost effectiveness analysis and cost utility), including both healthcare utilization and indirect costs.

Entry Criteria

Disease Characteristics:

• Histologically confirmed (primary lesion or regional lymph nodes) squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx
  • Locally advanced disease, defined by any of the following criteria:
    • Any T, N+, M0
    • T3-4, N0, M0



• No current history of unknown primary squamous cell carcinoma of the head and neck, primary nasopharyngeal, paranasal, or salivary gland tumors of the head and neck

Prior/Concurrent Therapy:

• No prior surgical treatment except diagnostic biopsy for this disease
• No prior induction chemotherapy for this disease
• No prior radiation to the head and neck region that would result in overlap of fields for this study
• No prior cisplatin or carboplatin chemotherapy
• No prior targeted anti-EGFR therapy of any kind
• At least 30 days since any prior investigational agent
• No concurrent granulocytic growth factors (e.g., filgrastim [G-CSF]) during radiotherapy
• No concurrent erythropoietic growth factors, pilocarpine, amifostine, other anticancer therapy (e.g., cytotoxic agents, biological response modifiers, immunotherapy, or hormonal therapy), or other investigational drug therapy

Patient Characteristics:

• ECOG performance status 0-1
• Absolute granulocyte count ≥ 1.5 x 10⁹/L
• Platelet count ≥ 100 x 10⁹/L
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST or ALT ≤ 3 times ULN
• Creatinine clearance > 50 mL/min
• Magnesium > 0.5 mmol/L
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment
• Must be accessible for treatment and follow-up
• Able (sufficiently fluent) and willing to complete the quality of life (QOL) and swallowing QOL questionnaires in either English or French
• Must be assessed by a radiation oncologist and medical oncologist and deemed suitable for study participation
• No other malignancies within the past 5 years, except adequately treated nonmelanoma skin cancer, curatively treated in-situ cancer of the cervix, or other curatively treated solid tumors
• No history of allergic or hypersensitivity reactions to any of the study drugs or their excipients
• No prior or concurrent interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) on baseline CT scan
• No peripheral neuropathy ≥ grade 2 (CTCAE v3.0)
• No hearing loss/tinnitus ≥ grade 3 (CTCAE v3.0)
• No thromboembolic event within the past 12 months despite being treated with anticoagulation drugs
  • Prior thromboembolic event > 12 months allowed provided patient is stable on anticoagulation or on preventative anticoagulation
• None of the following allowed:
  • Myocardial infarction within the past 12 months
  • Uncontrolled severe congestive heart failure
  • Unstable angina
  • Active cardiomyopathy
  • Unstable ventricular arrhythmia
  • Uncontrolled hypertension
  • Uncontrolled psychotic disorder
  • Active serious infection
  • Active peptic ulcer disease
  • Any other medical condition that might interfere with protocol therapy delivery

Expected Enrollment

Outcomes

Progression-free survival (PFS)

Overall survival
Local and regional PFS
Distant metastasis
Adverse events, including late radiotherapy-related adverse events as assessed by NCI CTCAE v3.0
Quality of life (QOL)
Swallowing-related (QOL)
Economic evaluation, including healthcare utilization, health utilities, and indirect costs

Outline

This is a multicenter study. Patients are stratified according to T category (T1-3 vs T4), nodal status (N0-1 vs N2 vs N3), radiotherapy delivery modality (intensity-modulated [IMRT] vs 3-D conformal [3D CRT]), anatomic location (hypopharynx vs oral cavity vs oropharynx vs larynx), and participation in the optional swallowing impairment substudy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo standard fractionation radiotherapy (IMRT or 3D CRT) once daily, 5 days a week, for 7 weeks. Patients receive cisplatin IV over 1 hour on days 1, 22, and 43 of radiotherapy.



• Arm II: Patients undergo accelerated fractionation radiotherapy (IMRT or 3D CRT) once or twice daily, 5 days a week, for 6 weeks. Patients receive panitumumab IV over 30-90 minutes 1 week prior to and on days 15 and 36 of radiotherapy.

Treatment in both arms continues in the absence of disease progression or unacceptable toxicity.

Quality of life (QOL) (FACT-H&N), swallowing-related QOL (MDADI, SWAL-QOL), swallowing function (FOIS), and economic evaluations (Lost Productivity questionnaire) are assessed periodically during the study.

After completion of study treatment, patients are followed periodically for at least 5 years.

Trial Contact Information

Trial Lead Organizations

NCIC-Clinical Trials Group

Lillian Siu, MD, FRCPC, Principal investigator		Ph: 416-946-2911
John Waldron, MD, Protocol co-chair		Ph: 416-946-6522

Canada
Ontario
	Toronto
	Princess Margaret Hospital
		Lillian Siu	Ph:  416-946-2911

Registry Information
Official Title		A Phase III Study of Standard Fractionation Radiotherapy with Concurrent High-Dose Cisplatin Versus Accelerated Fractionation Radiotherapy with Panitumumab in Patients with Locally Advanced Stage III and IV Squamous Cell Carcinoma of the Head and Neck
Trial Start Date		2008-12-31 (estimated)
Trial Completion Date		2012-03-31 (estimated)
Registered in ClinicalTrials.gov		NCT00820248
Date Submitted to PDQ		2008-12-10
Information Last Verified		2009-01-14