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

Phase 2

Completed

• Conditions: Cancer; Head and Neck Cancer; Oncology; Squamous Cell Carcinoma
• Interventions: Drug: Cisplatin; Drug: Panitumumab

• Registration Number: NCT00547157
• Lead Sponsor: Amgen

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)

Study Timeline

• Study First Submitted: 2007-10-18
• Study First Submitted QC: 2007-10-18
• Study First Posted: 2007-10-22
• Study Start: 2007-11
• Primary Completion: 2011-12
• Study Completion: 2012-03
• Results First Submitted: 2013-12-16
• Results First Submitted QC: 2014-04-23
• Results First Posted: 2014-05-23
• Status Verified: 2017-02
• Last Update Submitted: 2017-02-07
• Last Update Posted: 2017-03-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 152

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ARM 1 CRT	Cisplatin	Cisplatin plus RT
ARM 2 PRT	Panitumumab	Panitumumab plus RT

Primary Outcome Measures

Name	Time	Method
Local Regional Control Rate at 2 Years	from study day 1 to 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).

Secondary Outcome Measures

Name	Time	Method
Duration of Local Regional Control	maximum follow up time 46.2 months	Time from study day 1 to the date of first local-regional failure or to death due to any cause (whichever occurs first)
Progression-free Survival	maximum follow up time 46.2 months	Time from first dose date till disease progression or death
Overall Survival	maximum follow up time 46.2 months	Time from first dose date to death
ORR by 6 Months - Central	From randomization to 6 months	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.
CRR by 6 Months - Central	From randomization till 6 months	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.