Study of Addition of Panitumumab to Chemoradiation Therapy in Patients With Locally Advanced Head and Neck Cancer

Study Overview
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Brief Summary
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The addition of chemotherapy to radiotherapy (chemoradiation) has improved outcomes for patients with locally advanced squamous cell carcinoma of the head and neck but additional improvements to treatment regimens are needed. The study is investigating if the addition of a targeted therapy (panitumumab) can improve the efficacy of chemoradiation without adding unmanageable toxicity.

Official Title
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A Phase 2, Randomized Trial of Chemoradiation With or Without Panitumumab in Subjects With Unresected, Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Conditions
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Head and Neck Cancer, Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Cisplatin
* Radiation: Standard Fractionation Radiotherapy
* Drug: Panitumumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of Stage III or IVa-b (M0) squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (you must be well enough to receive chemoradiation therapy) You must be at least 18 years of age Your test results must show that your kidneys, liver and blood cells are working adequately and that, if you are female, you are not pregnant You must have measurable disease Exclusion Criteria: Cancer of the nasopharynx, sinus, salivary gland or skin History of another cancer (other than head and neck) unless treated with curative intent and with no evidence of disease for more than 3 years, with the exception of non-melanoma skin cancer or in situ cervical cancer Previous treatment with anti-endothelial growth factor receptor (EGFr) antibody therapy or EGFr inhibitors Previous treatment for head and neck cancer, with chemotherapy, surgery (except nodal sampling or biopsy) or radiotherapy Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) within one year before you join the study Chronic obstructive pulmonary disease (pneumonia or respiratory decompensation) resulting in hospitalization within 6 months of study screening History or evidence of interstitial lung disease (e.g. pneumonitis or pulmonary fibrosis) Major surgery within 28 days of screening

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panitumumab Plus Chemoradiation<br>Participants received standard radiation therapy for 7 weeks and cisplatin 75 mg/m^2 and panitumumab 9 mg/kg on Days 1, 22 and 43. | Drug: Cisplatin<br>* Administered intravenously (IV; in a vein)<br>Radiation: Standard Fractionation Radiotherapy<br>* 70 Gy administered in 2 Gy fractions daily for 5 days a week for 7 weeks (35 fractions)<br>Drug: Panitumumab<br>* Administered intravenously<br>* Other names: Vectibix®;|
| Active Comparator: Chemoradiotherapy Alone<br>Participants received standard radiation therapy for 7 weeks and cisplatin 100 mg/m^2 on Days 1, 22, and 43. | Drug: Cisplatin<br>* Administered intravenously (IV; in a vein)<br>Radiation: Standard Fractionation Radiotherapy<br>* 70 Gy administered in 2 Gy fractions daily for 5 days a week for 7 weeks (35 fractions)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Regional Control Rate at 2 Years | In this study participants were considered to be in local regional control (LRC) if there was no evidence of active disease in the previously affected/irradiated head-and-neck area. LRC could be achieved at any time following completion of treatment unless disease progression in the local-regional area occurred or the participant received subsequent anti-tumor therapy. Local regional control rate is defined as the Kaplan-Meier (KM) estimate of the proportion of participants with local regional control. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Regional Control Rate at 6 Months and 12 Months | Participants were considered to be in local regional control (LRC) if there was no evidence of active disease in the previously affected/irradiated head-and-neck area. LRC could be achieved at any time following completion of treatment unless disease progression in the local-regional area occurred or the participant received subsequent anti-tumor therapy. Local regional control rate is defined as the Kaplan-Meier (KM) estimate of the proportion of participants with local regional control. | 6 months and 12 months | 
| Duration of Local-regional Control | Duration of local regional control is calculated from the first day of any study treatment (radiotherapy, chemotherapy, or panitumumab) administration to the date of first local-regional failure or to death due to any cause (whichever occurs first). Local-regional failure includes persistent disease and local-regional recurrence of disease. Participants who did not meet the criteria for LRC recurrence after achieving a response by the analysis data cutoff date were censored at their last evaluable disease assessment date. Participants who never achieved LRC were considered to have a duration of 0. | From first dose up to 37 months | 
| Progression-Free Survival | Progression-free survival time is defined as time from the first day of any study treatment to date of first progresive disease using a modified version of the World Health Organization (WHO) criteria or death. Progressive Disease is defined as at least a 25% increase in the size of index lesions or unequivocal progression of existing non-index lesions or the presence of one or more new lesions. Participants not meeting these criteria by the cutoff date were censored at their last evaluable disease assessment date. | From first dose date to 37 months | 
| Overall Survival | Survival time is defined as time from the first day of any study treatment to date of death. Participants who had not died by the cutoff date were censored at their last contact date. | From first dose date up to 37 months | 
| Percentage of Participants With an Objective Response at 6 Months | Objective response by 6 months is defined as a complete response or partial response based on central review of scans using a a modification of the WHO criteria during the first 6 months. Complete Response (CR): Disappearance of all index and non-index lesions and no new lesions. Partial Response (PR): At least a 50% decrease in the size of index lesions with no progression in non-index lesions, or the disappearance of all index lesions and persistence of 1 or more non-index lesions not qualifying for either CR or progressive disease and no new lesions. | 6 months | 
| Percentage of Participants With a Complete Response at 6 Months | Response assessment based on central review of scans using a a modification of the WHO criteria, during the first 6 months. Complete Response is defined as the disappearance of all index and non-index lesions and no new lesions. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head and Neck Cancer, panitumumab