Radiation + Cisplatin or Panitumumab in Locally Advanced Stage III or Stage IV Head and Neck Cancer

Head and Neck Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00820248
• Other study ID #: HN6
• Secondary ID: CAN-NCIC-HN6CDR0
• Status: Completed
• Phase: Phase 3
• Start date: December 30, 2008
• Est. completion date: February 17, 2017

Study information

• Verified date: April 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy in higher doses over a shorter period of time may kill more tumor cells and have fewer side effects. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether giving standard radiation therapy together with high-dose cisplatin is more effective than giving higher-dose radiation therapy together with panitumumab in treating patients with locally advanced head and neck cancer. PURPOSE: This randomized phase III trial is comparing two radiation therapy regimens to see how well they work when given together with cisplatin or panitumumab in treating patients with locally advanced stage III or stage IV head and neck cancer.

Description:

OBJECTIVES: Primary - 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 - To compare overall survival of patients treated with these regimens. - To compare local and regional PFS of patients treated with these regimens. - To compare distant metastasis in patients treated with these regimens. - To compare adverse events, including late radiotherapy-related adverse events in patients treated with these regimens. - To compare quality of life (QOL) of patients treated with these regimens. - To compare swallowing-related QOL of patients treated with these regimens. - To compare economic evaluation (cost effectiveness analysis and cost utility), including both healthcare utilization 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 320
• Est. completion date: February 17, 2017
• Est. primary completion date: May 16, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically and/or cytologically 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

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Absolute granulocyte count = 1.5 x 10^9/L
• Platelet count = 100 x 10^9/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 psychiatric disorder
• Active serious infection
• Active peptic ulcer disease
• Any other medical condition that might interfere with protocol therapy delivery

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
• The following radiological investigations must be done within 8 weeks of

randomization:

• MRI or CT of the head and neck
• CT chest

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Biological:
• panitumumab
Given IV

Drug:
• cisplatin
Given IV

Radiation:
• 3-dimensional conformal radiation therapy
Patients undergo radiotherapy
• accelerated radiation therapy
Patients undergo accelerated fractionation radiotherapy
• intensity-modulated radiation therapy
Patients undergo radiotherapy

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	Cancer Centre of Southeastern Ontario at Kingston	Kingston	Ontario
Canada	London Regional Cancer Program	London	Ontario
Canada	Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	McGill University - Dept. Oncology	Montreal	Quebec
Canada	Ottawa Health Research Institute - General Division	Ottawa	Ontario
Canada	CHUQ-Pavillon Hotel-Dieu de Quebec	Quebec City	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Atlantic Health Sciences Corporation	Saint John	New Brunswick
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Centre hospitalier universitaire de Sherbrooke	Sherbrooke	Quebec
Canada	Dr. H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador
Canada	Northeast Cancer Center Health Sciences	Sudbury	Ontario
Canada	BCCA - Fraser Valley Cancer Centre	Surrey	British Columbia
Canada	Thunder Bay Regional Health Science Centre	Thunder Bay	Ontario
Canada	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba

Sponsors (1)

Lead Sponsor	Collaborator
NCIC Clinical Trials Group

Country where clinical trial is conducted

Canada, 

References & Publications (2)

Ringash J, Waldron JN, Siu LL, Martino R, Winquist E, Wright JR, Nabid A, Hay JH, Hammond A, Sultanem K, Hotte S, Leong C, El-Gayed AA, Naz F, Ramchandar K, Owen TE, Montenegro A, O'Sullivan B, Chen BE, Parulekar WR. Quality of life and swallowing with standard chemoradiotherapy versus accelerated radiotherapy and panitumumab in locoregionally advanced carcinoma of the head and neck: A phase III randomised trial from the Canadian Cancer Trials Group (HN.6). Eur J Cancer. 2017 Feb;72:192-199. doi: 10.1016/j.ejca.2016.11.008. Epub 2016 Dec 29. — View Citation

Siu LL, Waldron JN, Chen BE, Winquist E, Wright JR, Nabid A, Hay JH, Ringash J, Liu G, Johnson A, Shenouda G, Chasen M, Pearce A, Butler JB, Breen S, Chen EX, FitzGerald TJ, Childs TJ, Montenegro A, O'Sullivan B, Parulekar WR. Effect of Standard Radiother — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS) Rate	The progression event is defined by first event of the following,; Local-regional progression or recurrence Distant metastasis Non-protocol RT, chemotherapy, or biologic therapy without documentation of the site of failure Surgery of primary site with tumour present/unknown Neck dissection with tumour present/unknown, > 15 weeks from end of RT Death due to study cancer or from unknown causes or any other reason; Number of patients with and without progression event will be reported.	6.2 years
Secondary	Overall Survival Rate	Overall survival is defined as the time interval between the date of randomization to date of death from any cause (calculated in months). Otherwise, survival is censored at the last date that the patient is known to be alive.; Number of death and alive patients will be reported.	6.2 years