Radiation + Cisplatin or Panitumumab in Locally Advanced Stage III or Stage IV Head and Neck Cancer

August 3, 2023 updated by: NCIC Clinical Trials Group

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

320

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute
    • British Columbia
      • Surrey, British Columbia, Canada, V3V 1Z2
        • BCCA - Fraser Valley Cancer Centre
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • BCCA - Vancouver Cancer Centre
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 0V9
        • CancerCare Manitoba
    • New Brunswick
      • Saint John, New Brunswick, Canada, E2L 4L2
        • Atlantic Health Sciences Corporation
    • Newfoundland and Labrador
      • St. John's, Newfoundland and Labrador, Canada, AIB 3V6
        • Dr. H. Bliss Murphy Cancer Centre
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
        • Juravinski Cancer Centre at Hamilton Health Sciences
      • Kingston, Ontario, Canada, K7L 5P9
        • Cancer Centre of Southeastern Ontario at Kingston
      • London, Ontario, Canada, N6A 4L6
        • London Regional Cancer Program
      • Ottawa, Ontario, Canada, K1H 8L6
        • Ottawa Health Research Institute - General Division
      • Sudbury, Ontario, Canada, P3E 5J1
        • Northeast Cancer Center Health Sciences
      • Thunder Bay, Ontario, Canada, P7B 6V4
        • Thunder Bay Regional Health Science Centre
      • Toronto, Ontario, Canada, M5G 2M9
        • Univ. Health Network-Princess Margaret Hospital
    • Quebec
      • Montreal, Quebec, Canada, H2W 1S6
        • McGill University - Dept. Oncology
      • Montreal, Quebec, Canada, H1T 2M4
        • Hôpital Maisonneuve-Rosemont
      • Quebec City, Quebec, Canada, G1R 2J6
        • CHUQ-Pavillon Hotel-Dieu de Quebec
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • Centre Hospitalier Universitaire de Sherbrooke
    • Saskatchewan
      • Regina, Saskatchewan, Canada, S4T 7T1
        • Allan Blair Cancer Centre
      • Saskatoon, Saskatchewan, Canada, S7N 4H4
        • Saskatoon Cancer Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
Drug: cisplatin
Given IV
Radiation: 3-dimensional conformal radiation therapy
Patients undergo radiotherapy
Radiation: intensity-modulated radiation therapy
Patients undergo radiotherapy
Experimental: 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.
Radiation: 3-dimensional conformal radiation therapy
Patients undergo radiotherapy
Radiation: intensity-modulated radiation therapy
Patients undergo radiotherapy
Biological: panitumumab
Given IV
Radiation: accelerated radiation therapy
Patients undergo accelerated fractionation radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS) Rate
Time Frame: 6.2 years

The progression event is defined by first event of the following,

Local-regional progression or recurrence Distant metastasis Non-protocol RT, chemotherapy, or biologic therapy without documentation of the site of failure Surgery of primary site with tumour present/unknown Neck dissection with tumour present/unknown, > 15 weeks from end of RT Death due to study cancer or from unknown causes or any other reason

Number of patients with and without progression event will be reported.
6.2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival Rate
Time Frame: 6.2 years

Overall survival is defined as the time interval between the date of randomization to date of death from any cause (calculated in months). Otherwise, survival is censored at the last date that the patient is known to be alive.

Number of death and alive patients will be reported.
6.2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NCIC Clinical Trials Group

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 30, 2008

Primary Completion (Actual)

May 16, 2015

Study Completion (Actual)

February 17, 2017

Study Registration Dates

First Submitted

January 9, 2009

First Submitted That Met QC Criteria

January 9, 2009

First Posted (Estimated)

January 12, 2009

Study Record Updates

Last Update Posted (Actual)

August 22, 2023

Last Update Submitted That Met QC Criteria

August 3, 2023

Last Verified

April 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HN6
  • CAN-NCIC-HN6 (Registry Identifier: NCI US - Physician Data Query)
  • CDR0000630159 (Other Identifier: PDQ)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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