Radiotherapy Plus Panitumumab Compared to Chemoradiotherapy With Unresected, Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to estimate, with pre-specified precision, the difference in local-regional control (LRC) rate at 2 years in subjects receiving chemoradiotherapy (CRT) or panitumumab plus radiotherapy (PRT) as first line treatment for locally advanced squamous cell carcinoma for the head and neck (SCCHN). A formal hypothesis will not be tested in this trial; however, the treatment arm difference in LRC rates at 2 years will be estimated.

Detailed Description
-----------------
Primary Objective: To estimate, with pre-specified precision, the difference in local-regional control (LRC) rate at 2 years in subjects receiving chemoradiotherapy (CRT) or panitumumab plus radiotherapy (PRT) as first line treatment for locally advanced squamous cell carcinoma for the head and neck (SCCHN). Secondary Objectives: To estimate the difference between 2 treatment regimens (CRT vs PRT) on other measures of clinical benefit, including LRC, overall response rate (ORR), progression-free survival (PFS), overall survival (OS); and safety. Tertiary Objectives: To estimate the difference in health-related quality of life (HRQoL) and performance status in subjects receiving PRT or CRT. Exploratory Objectives: To investigate potential biomarker development based on assessment of blood and tumor and the proposed mechanism of actions of study drugs. In addition, to investigate the effect of genetic variation in cancer genes and drug target genes on SCCHN and subject response to study drugs (separate informed consent required). Hypothesis: A formal hypothesis will not be tested in this trial; however, the treatment arm difference in LRC rates at 2 years will be estimated. Study Design: This is a phase 2, open-label, randomized, multicenter study. Eligible subjects will be randomized in a 2:3 ratio to either of the following regimens: Arm 1 CRT: Accelerated fractionation RT: 70 to 72 Gy - delivered over 6 to 6.5 weeks Cisplatin: 100 mg/m2 (given on days 1 and 22 of RT) or Arm 2 PRT: Accelerated fractionation RT: 70 to 72 Gy - delivered over 6 to 6.5 weeks Panitumumab: 9.0 mg/kg Q3W (given on days 1, 22, and 43 of RT)

Official Title
-----------------
A Phase 2 Randomized Trial of Radiotherapy Plus Panitumumab Compared to Chemoradiotherapy With Unresected, Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Conditions
-----------------
Cancer, Head and Neck Cancer, Oncology, Squamous Cell Carcinoma

Intervention / Treatment
-----------------
* Drug: Panitumumab
* Drug: Cisplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed SCC of the oral cavity, oropharynx, hypopharynx or larynx Stage III or Stage IVa-b (M0) disease according to the American Joint Committee on Cancer staging manual 6th edition (locally advanced) ECOG performance status of 0 or 1 Bidimensionally measurable disease >/= 10 mm in at least 1 dimension Exclusion Criteria: NO Primary tumor of the nasopharynx, sinuses, salivary gland, or skin NO Subjects requiring prophylactic tracheostomy NO Prior (or concomitant) malignancy (except non-melanomatous skin cancer or in situ cervical cancer), other than the study disease (SCCHN), unless treated with curative intent with no evidence of disease for >/= 3 years NO Prior treatment for locally advanced SSCHN NO Prior surgery for SCCHN (except nodal sampling or biopsy for study disease) NO Major surgery </= 28 days before randomization or minor surgery </= 14 days before randomization with the exception of feeding tube placement, dental extractions, central venous catheter placement, biopsies and nodal sampling

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ARM 1 CRT<br>Cisplatin plus RT | Drug: Cisplatin<br>* Cisplatin<br>* Other names: Cisplatin (Chemotherapy);|
| Experimental: ARM 2 PRT<br>Panitumumab plus RT | Drug: Panitumumab<br>* Arm 2 consists of panitmumab plus RT<br>* Other names: Panitumumab (drug);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Regional Control Rate at 2 Years | Kaplan-Meier estimate of Local regional control rate at 2 years. Local regional control rate will be measured according to the investigator's assessment of disease status based on all available data (ie, from clinical examination, radiologic assessments, pathology reports, and autopsy reports). | from study day 1 to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Local Regional Control | Time from study day 1 to the date of first local-regional failure or to death due to any cause (whichever occurs first) | maximum follow up time 46.2 months | 
| Progression-free Survival | Time from first dose date till disease progression or death | maximum follow up time 46.2 months | 
| Overall Survival | Time from first dose date to death | maximum follow up time 46.2 months | 
| ORR by 6 Months - Central | ORR is Objective Response Rate. Tumor assessments are based on central review of scans uisng a modification of the WHO criteria. Complete or partial response is considered as objective response. | From randomization to 6 months | 
| CRR by 6 Months - Central | CRR is Complete Response Rate. Tumor assessments are based on central review of scans uisng a modification of the WHO criteria. Complete Response (CR) is defined as disappearance of all index lesions. | From randomization till 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
head and neck, squamous cell carcinoma, radiotherapy, chemoradiotherapy, panitumumab, locally advanced head & neck cancer, EGFr, epidermal growth factor receptor, SCCHN, locally advanced SCCHN, HNC, epidermal growth factor