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

Sponsored by:	National Cancer Institute of Canada
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00820248

Purpose

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.

Condition	Intervention	Phase
Head and Neck Cancer	Drug: cisplatin Drug: panitumumab Procedure: 3-dimensional conformal radiation therapy Procedure: accelerated radiation therapy Procedure: intensity-modulated radiation therapy	Phase III

MedlinePlus related topics: Cancer Head and Neck Cancer

Drug Information available for: Cisplatin Panitumumab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Progression-free survival (PFS) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival [ Designated as safety issue: No ]
Local and regional PFS [ Designated as safety issue: No ]
Distant metastasis [ Designated as safety issue: No ]
Adverse events, including late radiotherapy-related adverse events as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
Quality of life (QOL) [ Designated as safety issue: No ]
Swallowing-related (QOL) [ Designated as safety issue: No ]
Economic evaluation, including healthcare utilization, health utilities, and indirect costs [ Designated as safety issue: No ]

Estimated Enrollment:	320
Study Start Date:	December 2008
Estimated Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental 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.	Drug: cisplatin Given IV Procedure: 3-dimensional conformal radiation therapy Patients undergo radiotherapy Procedure: intensity-modulated radiation therapy Patients undergo radiotherapy
Arm II: Experimental 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.	Drug: panitumumab Given IV Procedure: 3-dimensional conformal radiation therapy Patients undergo radiotherapy Procedure: accelerated radiation therapy Patients undergo accelerated fractionation radiotherapy Procedure: intensity-modulated radiation therapy Patients undergo radiotherapy

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

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 psychotic 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00820248

Sponsors and Collaborators

National Cancer Institute of Canada

Investigators

Principal Investigator:	Lillian L. Siu, MD, FRCPC	Princess Margaret Hospital, Canada
Investigator:	John Waldron, MD	Princess Margaret Hospital, Canada

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000630159, CAN-NCIC-HN6
Study First Received:	January 9, 2009
Last Updated:	January 15, 2009
ClinicalTrials.gov Identifier:	NCT00820248
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

recurrent squamous cell carcinoma of the hypopharynx
recurrent squamous cell carcinoma of the larynx
recurrent verrucous carcinoma of the larynx
recurrent squamous cell carcinoma of the oropharynx
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
recurrent verrucous carcinoma of the oral cavity
recurrent squamous cell carcinoma of the lip and oral cavity
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

Study placed in the following topic categories:

Squamous cell carcinoma
Recurrence
Carcinoma
Epidermoid carcinoma
Cisplatin
Head and Neck Neoplasms
Carcinoma, squamous cell

Laryngeal carcinoma
Hypopharyngeal cancer
Neoplasms, Squamous Cell
Carcinoma, Squamous Cell
Carcinoma, squamous cell of head and neck
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Neoplasms by Histologic Type
Radiation-Sensitizing Agents

Antineoplastic Agents
Therapeutic Uses
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009