Clinical trial NCT00820248: Radiation + Cisplatin or Panitumumab in Locally Advanced Stage III or Stage IV Head and Neck Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Head and Neck Cancer
Keywords: stage III squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the larynx
stage III verrucous carcinoma of the larynx
stage III squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the larynx
stage IV verrucous carcinoma of the larynx
stage IV squamous cell carcinoma of the oropharynx
stage III verrucous carcinoma of the oral cavity
stage III squamous cell carcinoma of the lip and oral cavity
stage IV verrucous carcinoma of the oral cavity
stage IV squamous cell carcinoma of the lip and oral cavity
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
First posted: 2009-01-12
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-free Survival (PFS) Rate
timeFrame: 6.2 years
Secondary outcomes:
measure: Overall Survival Rate
timeFrame: 6.2 years
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Surrey
country: Canada
facility: BCCA - Fraser Valley Cancer Centre
state: British Columbia
city: Vancouver
country: Canada
facility: BCCA - Vancouver Cancer Centre
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Saint John
country: Canada
facility: Atlantic Health Sciences Corporation
state: New Brunswick
city: St. John's
country: Canada
facility: Dr. H. Bliss Murphy Cancer Centre
state: Newfoundland and Labrador
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre at Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Health Research Institute - General Division
state: Ontario
city: Sudbury
country: Canada
facility: Northeast Cancer Center Health Sciences
state: Ontario
city: Thunder Bay
country: Canada
facility: Thunder Bay Regional Health Science Centre
state: Ontario
city: Toronto
country: Canada
facility: Univ. Health Network-Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Hopital Maisonneuve-Rosemont
state: Quebec
city: Montreal
country: Canada
facility: McGill University - Dept. Oncology
state: Quebec
city: Quebec City
country: Canada
facility: CHUQ-Pavillon Hotel-Dieu de Quebec
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre hospitalier universitaire de Sherbrooke
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
Study officials:
affiliation: Princess Margaret Hospital, Canada
name: Lillian L. Siu, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: Princess Margaret Hospital, Canada
name: John Waldron, MD
role: STUDY_CHAIR
References:
citation: 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.
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 Radiotherapy With Cisplatin vs Accelerated Radiotherapy With Panitumumab in Locoregionally Advanced Squamous Cell Head and Neck Carcinoma: A Randomized Clinical Trial. JAMA Oncol. 2017 Feb 1;3(2):220-226. doi: 10.1001/jamaoncol.2016.4510.
citation: Cuffe S, Hon H, Tobros K, Espin-Garcia O, Brhane Y, Harland L, Fadhel E, Eng L, LaDelfa A, Waldron J, Siu LL, Chen BE, Xu W, Simmons C, Kassam Z, Montenegro A, Parulekar WR, Liu G. Cancer patients' acceptability of incorporating an epidemiology questionnaire within a clinical trial. Clin Trials. 2015 Jun;12(3):237-45. doi: 10.1177/1740774514568689. Epub 2015 Jan 29.