Chemotherapy and Radiation Therapy With or Without Panitumumab in Treating Patients Who Have Undergone Surgery for Advanced Hypopharyngeal Cancer, Oropharyngeal Cancer, Laryngeal Cancer, or Oral Cavity Cancer at High Risk of Recurrence

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Withdrawn

CT.gov ID

NCT01142414

Collaborator

(none)

Enrollment

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as cisplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. 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 chemotherapy given together with radiation therapy is more effective with or without panitumumab in treating patients with advanced cancer of the hypopharynx, oropharynx, larynx, or oral cavity.

PURPOSE: This randomized phase III trial is studying chemotherapy given together with radiation therapy to see how well it works compared with chemotherapy and radiation therapy given together with panitumumab in treating patients who have undergone surgery for advanced hypopharyngeal cancer, oropharyngeal cancer, laryngeal cancer, or oral cavity cancer at high risk of recurrence.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Biological: panitumumab Drug: cisplatin Drug: fluorouracil Other: laboratory biomarker analysis Procedure: adjuvant therapy Procedure: quality-of-life assessment Radiation: 3-dimensional conformal radiation therapy Radiation: intensity-modulated radiation therapy	Phase 3

Detailed Description

OBJECTIVES:

Primary

To determine if the addition of concurrently administered panitumumab to standard adjuvant chemoradiation, with 1 of 2 cisplatin-based regimens, significantly prolongs disease-free survival of patients with macroscopically completely resected, advanced squamous cell carcinoma of the hypopharynx, oropharynx, larynx, or oral cavity at high risk of recurrence.

Secondary

To determine if the pre-surgery dose of panitumumab will alter the RNA expression of several genes and that these changes will provide additional prognostic information that can be used in future patient management. (Exploratory)
Measure the differences in RNA expression by RNA microarray and the results analyzed to create a gene expression classifier that will be checked for outcome prediction by association with disease free survival and down regulation of the glucose metabolism as measured by FDG-PET. (Exploratory)
To create a European biobank of biological samples which can be used for future research projects in this disease. (Exploratory)
To predict radiation-induced normal tissue toxicity based on in vitro lymphocyte apoptosis test and SNPs analysis. (Exploratory)
To assess the impact of radiation-induced side effects (swallowing dysfunction and xerostomia) on patient's quality of life.

OUTLINE: This is a multicenter study. Patients are stratified by treatment center, radiotherapy technique (3D-CRT vs IMRT), chemotherapy regimen (European Organization for Research and Treatment of Cancer [EORTC]) vs Arbeitsgemeinschaft Radiology Oncology [ARO] schedule), tumor location (larynx vs oropharynx vs hypopharynx vs oral cavity), pN-stage (pN0-2 vs pN3), pT-stage (pT1-2 vs pT3-4), margin/extracapsular extension (ECE) status (ECE+ and margin < 5 mm vs ECE- and margin < 5 mm vs ECE+ and margin > 5 mm), biological pre-study participation (yes vs no), p16 status (positive vs negative vs indeterminable). Patients are randomized to 1 of 2 treatment arms.

Arm I (chemoradiotherapy): Within 4-8 weeks of surgery, patients undergo 3D-conformal or intensity-modulated radiotherapy once daily 5 days a week in weeks 1-7. Patients also receive concurrent chemotherapy comprising either cisplatin IV over 1-2 hours on days 1, 22, and 43 (EORTC schedule) OR cisplatin IV over 1-2 hours and fluorouracil IV over 24 hours on days 1-5 and 29-33 (ARO schedule), in the absence of disease progression or unacceptable toxicity.
Arm II (chemoradiotherapy plus panitumumab): Within 4-8 weeks of surgery, patients undergo 3D-conformal or intensity-modulated radiotherapy and receive concurrent chemotherapy (EORTC schedule or ARO schedule) as in arm I. Patients also receive panitumumab IV over 1 hour on days 1, 8, 15, 22, 29, 36, and 43.

Blood samples are collected periodically for biomarker correlative studies and translational research. Patients complete quality-of-life EORTC questionnaires QLQ-C30, QLQ-HN35, and PSS-HN periodically.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Randomized Phase III Trial on Postoperative Chemoradiation in Combination With Anti EGFR-Antibody Versus Postoperative Chemoradiation in Head and Neck Squamous Cell Carcinomas (HNSCC) With High Risk of Locoregional Recurrence

Outcome Measures

Primary Outcome Measures

Disease-free survival []

Secondary Outcome Measures

Overall survival []
Loco-regional control []
Cumulative incidence of and time to distant metastases []
Cumulative incidence of and time to second cancers (all sites) []
Incidence of acute and late toxicity (CTCAE version 4.0) []
Health-related quality of life []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed primary squamous cell carcinoma of the hypopharynx, oropharynx, larynx, or oral cavity
Stage pT1-2 pN+ or pT3-4 any pN (stage III-IVB) disease
No distant metastases
No recurrent disease
Resectable disease
Has undergone surgical resection of carcinoma
p16 immunohistochemistry assay performed on tissue sections taken during the surgical procedure
No laser surgery
Potentially at high-risk of locoregional recurrence, defined as fulfilling ≥ 1 of the following criteria:
Close surgical margins (i.e., margins 1 mm to < 5 mm)
R1-resection (< 1 mm) (R2 resection is considered as not eligible)
Extracapsular nodal extension
No nasopharynx, nasal cavity, or paranasal sinuses carcinomas

PATIENT CHARACTERISTICS:

WHO or ECOG performance status 0-1
Absolute neutrophils ≥ 1.5 x 10^9/L
Platelet count ≥ 100 x 10^9/L
Hemoglobin ≥ 10.0 g/dL
Bilirubin < 1.5 times upper limit of normal (ULN)
AST< 3 times ULN
Alkaline phosphatase < 3 times ULN
Calculated creatinine clearance ≥ 60 mL/min
Calcium ≤ 11.5 mg/dL or 2.9 mmol/L
Magnesium ≥ 1.2 mg/dL or 0.5 mmol/L
Fertile patients must use effective contraception methods during the study and for 6 months after the last treatment dose
Not pregnant or nursing
No known allergic or hypersensitivity reaction to any of the components of the study treatment
No other concurrent serious illnesses or medical conditions, including any of the following:
History or evidence of interstitial pneumonitis or pulmonary fibrosis
Unstable cardiac disease despite treatment
NYHA class III-IV congestive heart failure
Clinically significant abnormal ECG or LVEF below the institutional lower limit of normal
Known HIV infection or other conditions of persistent immunodeficiency
Significant neurologic or psychiatric disorders
Active uncontrolled infection
Active disseminated intravascular coagulation
Symptomatic peripheral neuropathy (CTCAE 4.0 "peripheral sensory neuropathy and paresthesia") ≥ grade 2 or ototoxicity (CTCAE 4.0 "hearing impaired") ≥ grade 2, unless due to trauma or mechanical impairment due to tumor mass
Other serious underlying medical conditions that could impair the ability of the patient to participate in the study
No other malignancy within the past 5 years other than basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix
Patients who are disease-free for > 5 years allowed
No known drug abuse
No psychological, familial, sociological (e.g., severe alcohol addiction expected to hamper protocol compliance), or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

PRIOR CONCURRENT THERAPY:

No prior chemotherapy or radiotherapy for carcinoma of the head and neck
No prior radiotherapy to the head and neck region
No prior exposure to EGFR pathway-targeting therapy
No participation in another interventional clinical trial within the past 30 days
No concurrent granulocyte colony-stimulating factor (G-CSF) or erythropoietin
No other concurrent investigational drugs and/or anticancer treatment

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

European Organisation for Research and Treatment of Cancer - EORTC

Investigators

Study Chair: Wilfried Budach, MD, Heinrich-Heine University, Duesseldorf
Study Chair: Hans Langendijk, University Medical Center Groningen
Study Chair: Carla Van Herpen, Universitair Medisch Centrum St. Radboud - Nijmegen