Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials
Text Size

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

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by:
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT01142414
First received: June 10, 2010
Last updated: January 13, 2012
Last verified: January 2012
History of Changes
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Cancer
Drug Information available for: Panitumumab
U.S. FDA Resources

Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Disease-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]
  • Loco-regional control [ Designated as safety issue: No ]
  • Cumulative incidence of and time to distant metastases [ Designated as safety issue: No ]
  • Cumulative incidence of and time to second cancers (all sites) [ Designated as safety issue: No ]
  • Incidence of acute and late toxicity (CTCAE version 4.0) [ Designated as safety issue: Yes ]
  • Health-related quality of life [ Designated as safety issue: No ]
Enrollment: 0
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.

  Eligibility
Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01142414

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 Centre Groningen
Study Chair: Carla Van Herpen Universitair Medisch Centrum St. Radboud - Nijmegen
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT01142414     History of Changes
Other Study ID Numbers: EORTC-22071-24071, EORTC-22071, EORTC-22071-24071, EU-21038, EUDRACT-2008-006180-36, AMGEN-EORTC-22071
Study First Received: June 10, 2010
Last Updated: January 13, 2012
Health Authority: Europe: not applicable - trial withdrawn

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
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 lip and oral cavity
 stage IV squamous cell carcinoma of the lip and oral cavity
stage III squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx
tongue cancer

ClinicalTrials.gov processed this record on March 03, 2015