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

Primary Purpose

Head and Neck Cancer

Status
Completed
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
panitumumab
cisplatin
3-dimensional conformal radiation therapy
accelerated radiation therapy
intensity-modulated radiation therapy
Sponsored by
NCIC Clinical Trials Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Cancer focused on measuring 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, 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Cross Cancer Institute
  • BCCA - Fraser Valley Cancer Centre
  • BCCA - Vancouver Cancer Centre
  • CancerCare Manitoba
  • Atlantic Health Sciences Corporation
  • Dr. H. Bliss Murphy Cancer Centre
  • Juravinski Cancer Centre at Hamilton Health Sciences
  • Cancer Centre of Southeastern Ontario at Kingston
  • London Regional Cancer Program
  • Ottawa Health Research Institute - General Division
  • Northeast Cancer Center Health Sciences
  • Thunder Bay Regional Health Science Centre
  • Univ. Health Network-Princess Margaret Hospital
  • Hopital Maisonneuve-Rosemont
  • McGill University - Dept. Oncology
  • CHUQ-Pavillon Hotel-Dieu de Quebec
  • Centre hospitalier universitaire de Sherbrooke
  • Allan Blair Cancer Centre
  • Saskatoon Cancer Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm I

Arm II

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Progression-free Survival (PFS) Rate
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.

Secondary Outcome Measures

Overall Survival Rate
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.

Full Information

First Posted
January 9, 2009
Last Updated
August 3, 2023
Sponsor
NCIC Clinical Trials Group
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1. Study Identification

Unique Protocol Identification Number
NCT00820248
Brief Title
Radiation + Cisplatin or Panitumumab in Locally Advanced Stage III or Stage IV Head and Neck Cancer
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
December 30, 2008 (Actual)
Primary Completion Date
May 16, 2015 (Actual)
Study Completion Date
February 17, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NCIC Clinical Trials Group

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancer
Keywords
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, 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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
320 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Active Comparator
Arm Description
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 Title
Arm II
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
panitumumab
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
cisplatin
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
3-dimensional conformal radiation therapy
Intervention Description
Patients undergo radiotherapy
Intervention Type
Radiation
Intervention Name(s)
accelerated radiation therapy
Intervention Description
Patients undergo accelerated fractionation radiotherapy
Intervention Type
Radiation
Intervention Name(s)
intensity-modulated radiation therapy
Intervention Description
Patients undergo radiotherapy
Primary Outcome Measure Information:
Title
Progression-free Survival (PFS) Rate
Description
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.
Time Frame
6.2 years
Secondary Outcome Measure Information:
Title
Overall Survival Rate
Description
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.
Time Frame
6.2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lillian L. Siu, MD, FRCPC
Organizational Affiliation
Princess Margaret Hospital, Canada
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
John Waldron, MD
Organizational Affiliation
Princess Margaret Hospital, Canada
Official's Role
Study Chair
Facility Information:
Facility Name
Cross Cancer Institute
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
BCCA - Fraser Valley Cancer Centre
City
Surrey
State/Province
British Columbia
ZIP/Postal Code
V3V 1Z2
Country
Canada
Facility Name
BCCA - Vancouver Cancer Centre
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada
Facility Name
CancerCare Manitoba
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3E 0V9
Country
Canada
Facility Name
Atlantic Health Sciences Corporation
City
Saint John
State/Province
New Brunswick
ZIP/Postal Code
E2L 4L2
Country
Canada
Facility Name
Dr. H. Bliss Murphy Cancer Centre
City
St. John's
State/Province
Newfoundland and Labrador
ZIP/Postal Code
AIB 3V6
Country
Canada
Facility Name
Juravinski Cancer Centre at Hamilton Health Sciences
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
Facility Name
Cancer Centre of Southeastern Ontario at Kingston
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 5P9
Country
Canada
Facility Name
London Regional Cancer Program
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4L6
Country
Canada
Facility Name
Ottawa Health Research Institute - General Division
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
Northeast Cancer Center Health Sciences
City
Sudbury
State/Province
Ontario
ZIP/Postal Code
P3E 5J1
Country
Canada
Facility Name
Thunder Bay Regional Health Science Centre
City
Thunder Bay
State/Province
Ontario
ZIP/Postal Code
P7B 6V4
Country
Canada
Facility Name
Univ. Health Network-Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Hopital Maisonneuve-Rosemont
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Facility Name
McGill University - Dept. Oncology
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2W 1S6
Country
Canada
Facility Name
CHUQ-Pavillon Hotel-Dieu de Quebec
City
Quebec City
State/Province
Quebec
ZIP/Postal Code
G1R 2J6
Country
Canada
Facility Name
Centre hospitalier universitaire de Sherbrooke
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1H 5N4
Country
Canada
Facility Name
Allan Blair Cancer Centre
City
Regina
State/Province
Saskatchewan
ZIP/Postal Code
S4T 7T1
Country
Canada
Facility Name
Saskatoon Cancer Centre
City
Saskatoon
State/Province
Saskatchewan
ZIP/Postal Code
S7N 4H4
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
28040660
Citation
Ringash J, Waldron JN, Siu LL, Martino R, Winquist E, Wright JR, Nabid A, Hay JH, Hammond A, Sultanem K, Hotte S, Leong C, El-Gayed AA, Naz F, Ramchandar K, Owen TE, Montenegro A, O'Sullivan B, Chen BE, Parulekar WR. Quality of life and swallowing with standard chemoradiotherapy versus accelerated radiotherapy and panitumumab in locoregionally advanced carcinoma of the head and neck: A phase III randomised trial from the Canadian Cancer Trials Group (HN.6). Eur J Cancer. 2017 Feb;72:192-199. doi: 10.1016/j.ejca.2016.11.008. Epub 2016 Dec 29.
Results Reference
background
PubMed Identifier
27930762
Citation
Siu LL, Waldron JN, Chen BE, Winquist E, Wright JR, Nabid A, Hay JH, Ringash J, Liu G, Johnson A, Shenouda G, Chasen M, Pearce A, Butler JB, Breen S, Chen EX, FitzGerald TJ, Childs TJ, Montenegro A, O'Sullivan B, Parulekar WR. Effect of Standard Radiotherapy With Cisplatin vs Accelerated Radiotherapy With Panitumumab in Locoregionally Advanced Squamous Cell Head and Neck Carcinoma: A Randomized Clinical Trial. JAMA Oncol. 2017 Feb 1;3(2):220-226. doi: 10.1001/jamaoncol.2016.4510.
Results Reference
result
PubMed Identifier
25633805
Citation
Cuffe S, Hon H, Tobros K, Espin-Garcia O, Brhane Y, Harland L, Fadhel E, Eng L, LaDelfa A, Waldron J, Siu LL, Chen BE, Xu W, Simmons C, Kassam Z, Montenegro A, Parulekar WR, Liu G. Cancer patients' acceptability of incorporating an epidemiology questionnaire within a clinical trial. Clin Trials. 2015 Jun;12(3):237-45. doi: 10.1177/1740774514568689. Epub 2015 Jan 29.
Results Reference
derived

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

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