Radiation Therapy and Cisplatin With or Without Cetuximab in Treating Patients With Stage III or Stage IV Head and Neck Cancer - Full Text View

Sponsor:	Radiation Therapy Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00265941

Purpose

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. 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. Cisplatin may also make tumor cells more sensitive to radiation therapy. Monoclonal antibodies, such as cetuximab, 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. Giving radiation therapy and cisplatin together with cetuximab may kill more tumor cells. It is not yet known whether radiation therapy and cisplatin are more effective with or without cetuximab in treating head and neck cancer.

PURPOSE: This randomized phase III trial is studying radiation therapy, cisplatin, and cetuximab to see how well they work compared to radiation therapy and cisplatin in treating patients with stage III or stage IV head and neck cancer.

Condition	Intervention	Phase
Head and Neck Cancer	Biological: cetuximab Drug: cisplatin	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Masking: Open Label Primary Purpose: Treatment
Official Title:	A Randomized Phase III Trial of Concurrent Accelerated Radiation and Cisplatin Versus Concurrent Accelerated Radiation, Cisplatin, and Cetuximab (C225) [Followed by Surgery for Selected Patients] for Stage III and IV Head and Neck Carcinomas

Resource links provided by NLM:

MedlinePlus related topics: Cancer Head and Neck Cancer

Drug Information available for: Cisplatin Cetuximab

U.S. FDA Resources

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

Primary Outcome Measures:

Disease-free survival (DFS) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival (OS) [ Designated as safety issue: No ]
Local-regional control (LRC) [ Designated as safety issue: No ]
Mucositis toxicity ≥ grade 3 [ Designated as safety issue: Yes ]
Other toxicity ≥ grade 3 [ Designated as safety issue: Yes ]
Protocol treatment delivery [ Designated as safety issue: No ]
Death ≤ 30 days after discontinuation of protocol treatment [ Designated as safety issue: Yes ]
Quality of life as measured by Performance Status Scale for Head and Neck Cancer and the European Quality of Life questionnaire (EQ-5D) [ Designated as safety issue: No ]
Quality of life as measured by Functional Assessment of Cancer Therapy-General version [ Designated as safety issue: No ]
Correlation of expression of epidermal growth factor receptor or its down-stream molecules (e.g., MAPK, AKT, Stat-3, PKC) with DFS, OS, and LRC [ Designated as safety issue: No ]
Correlation of pre-treatment positron emission tomography (PET)/CT scan findings with DFS, OS, and LRC [ Designated as safety issue: No ]
Correlation of post-treatment PET/CT scan findings with pathologic nodal complete response and nodal relapse rate at 2 years in clinical N2-3 patients [ Designated as safety issue: No ]

Estimated Enrollment:	720
Study Start Date:	November 2005
Estimated Primary Completion Date:	June 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Arm I Patients receive cisplatin IV over 1 hour on days 1 and 22 (weeks 1 and 4) during radiotherapy.	Drug: cisplatin Given IV
Experimental: Arm II Patients receive cetuximab IV over 1-2 hours once in weeks 0-7 and cisplatin as in arm I.	Biological: cetuximab Given IV Drug: cisplatin Given IV

Detailed Description:

OBJECTIVES:

Primary

Evaluate whether the addition of cetuximab to a concurrent radiation-cisplatin regimen will improve disease-free survival in patients with stage III or IV squamous cell carcinoma of the oropharynx, hypopharynx, or larynx.

Secondary

Determine the impact of the addition of cetuximab to a concurrent radiation-cisplatin regimen on overall survival, local-regional control, acute and late toxic effects, quality of life, and health utilities in these patients.
Correlate the expression of EGFR and its down-stream molecules with outcome in patients participating in this component of the trial.
Correlate pre-treatment PET scan findings with disease-free survival, overall survival, and local-regional control in patients participating in this component of the trial.
Correlate post-treatment PET scan findings with nodal response and nodal relapse in patients participating in this component of the trial.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to primary site (larynx vs non-larynx), nodal stage (N0 vs N1, N2a, N2b vs N2c, N3), Zubrod performance status (0 vs 1), use of intensity modulated radiotherapy (IMRT) (no vs yes), and pre-treatment PET/CT scan (no vs yes). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients undergo either 3D-conformal radiotherapy or IMRT once or twice a day, 5 or 6 days a week, for 6 weeks. Patients also receive cisplatin IV over 1 hour on days 1 and 22 (weeks 1 and 4) during radiotherapy.
Arm II: Patients receive cetuximab IV over 1-2 hours once in weeks 0-7. Beginning in week 1, patients also undergo radiotherapy and receive cisplatin as in arm I.

In both arms, patients with persistent nodal disease (any stage) (i.e., a residual palpable or radiographic abnormality) undergo neck dissection* approximately 9-10 weeks after completion of treatment.

NOTE: *A neck dissection is optional for patients with multiple lymph nodes or lymph nodes > 3 cm in diameter who achieve a complete clinical and radiographic response in the neck.

Quality of life is assessed at baseline, once during the last 2 weeks of treatment, at 3 and 12 months from the start of treatment, and then annually for 4 years.

After completion of study treatment, patients are followed periodically for 5 years and then annually thereafter.

PROJECTED ACCRUAL: Approximately 720 patients will be accrued for this study.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically proven (from primary lesion and/or lymph nodes) squamous cell carcinoma of the oropharynx, hypopharynx, or larynx
- Stage III or IV disease (T2, N2-3, M0; T3-4, any N, M0)
  - No distant metastases
- The following primary tumor sites are excluded:
  - Oral cavity
  - Nasopharynx
  - Sinuses
  - Salivary glands

PATIENT CHARACTERISTICS:

Zubrod performance status 0-1
Absolute neutrophil count (ANC) ≥ 1,800/mm^3
Platelets ≥ 100,000/mm^3
Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention to achieve Hgb ≥ 8.0 g/dL is acceptable)
Bilirubin ≤ 1.5 mg/dL (Gilbert's disease as the sole cause of elevated bilirubin may be allowed at the discretion of the principal investigator)
AST or ALT ≤ 2 times the upper limit of normal
Serum creatinine ≤ 1.5 mg/dL
Creatinine clearance ≥ 50 mL/min
Not pregnant or nursing
Negative pregnancy test
Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study (until at least 60 days following the last study treatment)
No prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years
No unstable angina and/or congestive heart failure requiring hospitalization in past 6 months
Left ventricular ejection fraction ≥ 45%
No transmural myocardial infarction within the last 6 months
No acute bacterial or fungal infection requiring intravenous antibiotics
No chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy
No acquired immune deficiency syndrome (AIDS)
- HIV testing is not required for entry into this protocol
- Protocol-specific requirements may also exclude immuno-compromised patients
No prior allergic reaction to the study drug(s)
No other uncontrolled condition, which in the opinion of the investigator, would interfere in the safe and timely completion of study procedures
No comorbidity of uncontrolled diabetes (i.e., symptomatic hyperglycemia)
No other severe active comorbidity

PRIOR CONCURRENT THERAPY:

No prior systemic chemotherapy for the study cancer
- Prior chemotherapy for a different cancer is allowed
No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
No initial surgical treatment (excluding diagnostic biopsy of the primary site or nodal sampling of neck disease)
No radical or modified neck dissection
No prior therapy that specifically and directly targets the EGFR pathway

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00265941

Show 372 Study Locations

Sponsors and Collaborators

Radiation Therapy Oncology Group

National Cancer Institute (NCI)

Investigators

Principal Investigator:

K. Kian Ang, MD, PhD

M.D. Anderson Cancer Center

More Information

Additional Information:

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

Featured trial article This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Walter John Curran, Jr, Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:	NCT00265941 History of Changes
Other Study ID Numbers:	CDR0000458049, RTOG-0522
Study First Received:	December 14, 2005
Last Updated:	September 8, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

stage III squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the larynx

stage IV squamous cell carcinoma of the larynx
stage III squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx

Additional relevant MeSH terms:

Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Cetuximab
Cisplatin

Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 09, 2012